ArticleLiterature Review

Effects of probiotics on body adiposity and cardiovascular risk markers in individuals with overweight and obesity: A systematic review and meta-analysis of randomized controlled trials

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Background & Aims Evidence suggests that gut microbiota is a potential factor in the pathophysiology of both obesity and related metabolic disorders. While individual randomized controlled trials (RCTs) have evaluated the effects of probiotics on adiposity and cardiovascular disease (CVD) risk factors in subjects with overweight and obesity, the results are inconsistent. Thus, this systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation on body weight, body adiposity and CVD risk markers in overweight and obese subjects. Methods A systematic search for RCTs published up to December 2020 was conducted in MEDLINE (via PubMed), EMBASE, Scopus and LILACS. Meta-analysis using a random-effects model was chosen to analyze the impact of combined trials. Results Twenty-six RCTs (n=1720) were included. Data pooling showed a significant effect of probiotics in reducing body weight (MD:-0.70kg; 95%CI:-1.04,-0.35kg; P<0.0001), body mass index (BMI) (MD:-0.24kg/m²; 95%CI:-0.35,-0.12kg/m²; P=0.0001), waist circumference (WC) (MD:-1.13cm; 95%CI:-1.54,-0.73cm; P<0.0001), fat mass (MD:-0.71kg; 95%CI:-1.10,-0.32kg; P=0.0004), tumor necrosis factor-α (MD:-0.16pg/ml; 95%CI:-0.24,-0.08pg/ml; P=0.0001), insulin (MD:-0.85mcU/ml; 95%CI:-1.50,-0.21mcU/ml; P=0.010), total cholesterol (MD:-0.16mmol/l; 95%CI:-0.26,-0.05mmol/l; P=0.003) and LDL (MD:-0.09mmol/l; 95%CI:-0.16,-0.03mmol/l; P=0.006) compared with control groups. There was a significant decrease in body weight, BMI and WC in studies using both single and multi-bacterial species. Decreases in body adiposity parameters were only observed in studies using a probiotic dose of ≥ 10¹⁰ CFU and for ≥ 8 weeks duration. Conclusions The present meta-analysis suggests that probiotics consumption may be helpful for improving body weight, body adiposity and some CVD risk markers in individuals with overweight and obesity. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42020183136.

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... In the studies in which the effect on fat mass was reported, ten presented the results as fat mass percentage (%) (20-24, 26, 29, 30, 32, 34) and six as absolute fat mass (Kg) (25, 27-29, 31, 33), whereas one reported both parameters (29). Likewise, fourteen clinical trials measured the effect on muscle mass: four presented the results as changes in muscle mass (%) (20,21,32,34), seven as muscle mass (Kg) (28,31,32,34,35,37,39) and two as appendicular skeletal mass (kg) (23,24). Likewise, one study reported fat free mass (kg) (27). ...
... In contrast, Pontes et al. conducted two meta-analyses, one of which included eight studies that reported changes in fat mass (%) and observed a statistically significant decrease. Likewise, in the other meta-analysis on thirteen studies, the authors reported a decrease in fat mass (kg), with a greater effect when the probiotics consumed were of a single species, dose ≥10 10 (CFU/day), and duration ≥8 weeks (39). These results are not entirely reliable since the authors grouped and added data from all the studies without considering the heterogeneity regarding the type, dose, and treatment time of the probiotics. ...
... Of these, only two found statistically significant differences between the groups (35,37). In contrast, Pontes et al. (2021), who conducted a meta-analysis, reported a decrease in BMI (kg/m 2 ) in the group that consumed probiotics compared to the control (39). However, the authors did not meet the criteria of homogeneity of the studies in terms of type, dose, and treatment duration of probiotics, which justifies their inclusion in a meta-analysis. ...
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Background/Aim Probiotics are living microorganisms that confer health benefits when administered in adequate amounts. Several studies have shown the positive effects on body fat, muscle mass, and body mass index (BMI) in young adults and athletes; however, the results in adults aged ≥45 years are not conclusive. Materials and Methods A systematic review was conducted in accordance with the PRISMA guidelines, analyzing studies up to December 10, 2024, from nine databases (PubMed, Scopus, Web of Science, LILACS, SciELO, Springer, Redalyc, Cochrane Library and TESIUNAM). Mean differences (MD) were estimated using RevMan V 5.4.1. software. Results Six hundred and sixty-six studies were identified, of which 15 met the eligibility criteria. A statistically significant decrease in fat mass (%) was found in two studies and in fat mass (kg) in another two studies. Likewise, one study reported a statistically significant increase in skeletal muscle mass. Conclusion Probiotic supplementation may have a beneficial effect on reducing body fat mass and increasing or preventing skeletal muscle mass loss in adults ≥45 years old; however, further clinical trials are needed to determine the optimal types, doses, and duration of probiotic treatment for best results.
... Specifically, they have been found to enhance intestinal homeostasis, intestinal barrier function, host immunity, gut microbiome, and metabolome modulation (Ma et al., 2023). Recent meta-analyses have also shown that probiotic intake can have health-promoting effects on body adiposity and glycemic and lipid levels in overweight or obesity (Mayta-Tovalino et al., 2023;Perna et al., 2021;Pontes et al., 2021;Tomé-Castro et al., 2021). However, sex-specific clinical guidelines for the treatment of overweight/obesity in women are lacking, as most recommendations are based on findings in the general population. ...
... Several meta-analyses have evaluated the effects of probiotics on body adiposity in overweight or obese adults; however, the results obtained are inconsistent (Borgeraas et al., 2018;Mayta-Tovalino et al., 2023;Perna et al., 2021;Pontes et al., 2021;Tomé-Castro et al., 2021). This variability may be due to the different sex composition of the participants in the included studies. ...
... These findings indicated that probiotics may improve insulin sensitivity in women. Although insulin sensitivity differs between men and women (Regensteiner and Reusch, 2022), our results are consistent with those of previous meta-analyses that did not differentiate between the sexes (Pontes et al., 2021). A possible mechanism is that probiotics increase the production of SCFA, which activate G protein-coupled receptors (FFAR2 and FFAR3) on gut enteroendocrine L cells. ...
Article
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Our meta-analysis aimed to assess the effectiveness of probiotics in weight loss and glucose and lipid metabolism in overweight or obese women. PubMed, EMBASE, Cochrane Library, and Web of Science were used from inception until March 2024 to identify randomized controlled trials (RCT's) literature. Finally, 11 RCTs were included. Following critical appraisal, a meta-analysis was conducted using the fixed effects model and the random effects model found that probiotic consumption significantly decreased waist circumference (WC) (SMD = −0.39 cm, 95% CI: −0.60, −0.18 cm, P < 0.00001, I² = 33%), insulin (SMD = −0.45 mcU/ml; 95% CI: −0.72, −0.18 mcU/ml; P = 0.04, I² = 40%) and low-density lipoprotein cholesterol (LDL-C) levels (SMD = −0.51 mmol/L; 95% CI: −0.92, −0.11 mmol/L; P = 0.02, I² = 75%) in overweight or obese women. Moreover, subgroup analyses revealed that the effects of probiotic supplementation were significantly influenced by the intervention duration and diet and/or exercise intervention. This meta-analysis suggested that probiotic supplementation has a moderate and statistically significant effect on weight loss and glucose and lipid metabolism in overweight and obese women.
... The research primarily concentrated on obese individuals with NAFLD aged one day to 85 years old. The main measured indicators were body weight (23,28,56,59,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85), BMI (23,28,56,59,60,65,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82), WC (28, 68, 70, 72, 75, 79-81, 85, 87, 90, 93, 94, 99, 101), hip circumference (HC) (90), waist to hip ratio (WHR) (78,80,90,94), body fat percent (BF%) (71,75,80,85,90,94), and BFM (56,61,71,72,75,80,81,90). Probiotic supplementation significantly reduced weight, BMI, WC, BF%, and BFM across most studies. However, investigations into the impact of probiotic intake on variables such as HC (90) and percentage of excess weight loss (%EWL) (76, 105) revealed neutral effects on these measurements. ...
... The research primarily concentrated on obese individuals with NAFLD aged one day to 85 years old. The main measured indicators were body weight (23,28,56,59,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85), BMI (23,28,56,59,60,65,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82), WC (28, 68, 70, 72, 75, 79-81, 85, 87, 90, 93, 94, 99, 101), hip circumference (HC) (90), waist to hip ratio (WHR) (78,80,90,94), body fat percent (BF%) (71,75,80,85,90,94), and BFM (56,61,71,72,75,80,81,90). Probiotic supplementation significantly reduced weight, BMI, WC, BF%, and BFM across most studies. However, investigations into the impact of probiotic intake on variables such as HC (90) and percentage of excess weight loss (%EWL) (76, 105) revealed neutral effects on these measurements. ...
... The research primarily concentrated on obese individuals with NAFLD aged one day to 85 years old. The main measured indicators were body weight (23,28,56,59,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85), BMI (23,28,56,59,60,65,(69)(70)(71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82), WC (28, 68, 70, 72, 75, 79-81, 85, 87, 90, 93, 94, 99, 101), hip circumference (HC) (90), waist to hip ratio (WHR) (78,80,90,94), body fat percent (BF%) (71,75,80,85,90,94), and BFM (56,61,71,72,75,80,81,90). Probiotic supplementation significantly reduced weight, BMI, WC, BF%, and BFM across most studies. However, investigations into the impact of probiotic intake on variables such as HC (90) and percentage of excess weight loss (%EWL) (76, 105) revealed neutral effects on these measurements. ...
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Background There is controversial data on the effects of prebiotic, probiotic, or synbiotic supplementations on overweight/obesity indicators. Thus, we aimed to clarify this role of biotics through an umbrella review of the trials’ meta-analyses. Methods All meta-analyses of the clinical trials conducted on the impact of biotics on overweight/obesity indicators in general populations, pregnant women, and infants published until June 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. The meta-analysis of observational and systematic review studies without meta-analysis were excluded. We reported the results by implementing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart. The Assessment of Multiple Systematic Reviews-2 (AMSTAR2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence. Results Overall, 97 meta-analysis studies were included. Most studies were conducted on the effect of probiotics in both genders. Consumption of prebiotic: 8-66 g/day, probiotic: 10⁴ -1.35×10¹⁵ colony-forming unit (CFU)/day, and synbiotic: 10⁶-1.5×10¹¹ CFU/day and 0.5-300 g/day for 2 to 104 weeks showed a favorable effect on the overweight/obesity indicators. Moreover, an inverse association was observed between biotics consumption and overweight/obesity risk in adults in most of the studies. Biotics did not show any beneficial effect on weight and body mass index (BMI) in pregnant women by 6.6×10⁵-10¹⁰ CFU/day of probiotics during 1-25 weeks and 1×10⁹-112.5×10⁹ CFU/capsule of synbiotics during 4-8 weeks. The effect of biotics on weight and BMI in infants is predominantly non-significant. Prebiotics and probiotics used in infancy were from 0.15 to 0.8 g/dL and 2×10⁶-6×10⁹ CFU/day for 2-24 weeks, respectively. Conclusion It seems biotics consumption can result in favorable impacts on some anthropometric indices of overweight/obesity (body weight, BMI, waist circumference) in the general population, without any significant effects on birth weight or weight gain during pregnancy and infancy. So, it is recommended to intake the biotics as complementary medications for reducing anthropometric indices of overweight/obese adults. However, more well-designed trials are needed to elucidate the anti-obesity effects of specific strains of probiotics.
... In many clinical trials, probiotic was shown to have a beneficial effect and could be a potential treatment for overweight patients [26][27][28], pregnant women [29], and diabetes patients [30,31]. A systematic review showed the administration of probiotics could reduce body adiposity and improve the serum level of insulin, total cholesterol, and lipoprotein cholesterol in overweight and obese adults [32]. Postmenopausal women with obesity as a particular group facing a higher risk for cardiovascular diseases attracted researchers' attention to evaluating the effect of probiotic supplementation. ...
... This review showed that the administration of probiotics could reduce BMI (MD = − 0.34 kg/m 2 ), but the reduction is not significant (p = 0.07). Previous reviews aimed at whole overweight and obese adults showed a similar decrease in BMI [32,51,52]. Although a few studies showed a statistically significant effect, these reductions were modest. ...
... It revealed that oral probiotic supplementation may be a mild complementary treatment to decrease the BMI in overweight and obese people. Pontes et al. [32] found that a decrease in BMI was observed only with probiotic supplementation combined with diet energy restriction. All included studies in our review were not accompanied by energy restriction in the usual diet, which may be related to a nonsignificant reduction in BMI. ...
Article
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Gut microbiota has been identified as a unique endocrine organ linked to the development of cardiovascular disease and other illnesses, especially deteriorated in overweight and obese postmenopausal women. The object of this systematic review and meta-analysis aimed to assess the effects of oral supplementation with probiotics for overweight and obese postmenopausal women. We performed a systematic search for randomized controlled trials (RCTs) from inception to April 2022 in MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. We also performed a hand search by reviewing reference lists to identify trials. The risk of bias in individual studies was assessed with the Cochrane risk of bias tool for randomized trials (RoB). Two reviewers independently selected studies and collected data. There were 6 studies from 5 RCTs with 281 participants in this systematic review. Compared with the placebo, the probiotics supplementation group had reductions in insulin (MD − 4.20 IU/L (95% CI − 8.11 to − 0.30 IU/L), I2 = 54%), HOMA-IR (MD − 1.25 (95% CI − 2.49 to − 0.01), I2 = 50%), and TNF-α (MD − 0.12 pg/mL (95% CI − 0.22 to − 0.01 pg/mL), I2 = 44%). Improvements were also shown in body adiposity and lipid profile, but these effects were nonsignificant. In addition to body adiposity and cardiovascular risk markers, one trial showed the administration of probiotics also had an effect on iron metabolism. In conclusion, probiotics have a potential benefit on glucose metabolism and inflammatory process in overweight and obese postmenopausal women, but this effect is mild. It demonstrates that oral probiotics supplementation can be a complementary treatment for improving the fitness of postmenopausal women with overweight and obesity.
... kg/m 2 ) but the reduction is not signi cant (p = 0.07). In previous review aimed at overweight or obese adults, including male and female, Pontes et al. [31] presented a signi cant decrease which was 0.24 kg/m 2 , Wang et al. [32] shown a signi cant reduction of 0.3 kg/m 2 , Borgeraas et al. [33] shown an nonsigni cant reduction of 0.27 kg/m 2 . This disagreement may be related to the inclusion of newest clinical trials in Pontes et al. [31], such as Hajipoor [34], Majewska [28], Michael [35], Skrypnik [9] et al. ...
... In previous review aimed at overweight or obese adults, including male and female, Pontes et al. [31] presented a signi cant decrease which was 0.24 kg/m 2 , Wang et al. [32] shown a signi cant reduction of 0.3 kg/m 2 , Borgeraas et al. [33] shown an nonsigni cant reduction of 0.27 kg/m 2 . This disagreement may be related to the inclusion of newest clinical trials in Pontes et al. [31], such as Hajipoor [34], Majewska [28], Michael [35], Skrypnik [9] et al. Our studies included a clinical trial published in 2021 [27] which not included in before reviews. ...
... Energy restriction is the necessary condition for BMI decrease [32], all studies designed in overweight or obese postmenopausal women weren't accompanied with intervention restriction, this may be related to our non-signi cant result. Agreement with Karine's funding [31], our study showed a reduction in serum insulin and HOMA-IR level, suggesting a possible bene cial role in the sensitivity of insulin. The effect of probiotics on glucose was not signi cant, it's also consisted with previous study [31]. ...
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Gut microbiota has been identified as a unique endocrine organ that linked to the development of cardiovascular disease and other illnesses that deteriorated in overweight or obese postmenopausal women. The object of this systematic review and meta-analysis was to assess the effects of the oral supplementation with probiotics for overweight or obese postmenopausal women. We made a systematic search for randomized controlled trials (RCTs) from published to April 2022 in MEDLINE, EMBASE, Cochrane library, Web of science and ClinicalTrials.gov. The risks of bias in individual studies was assessed with the Cochrane risk of bias tool for randomized trials (RoB 2.0). Two reviewers independently selected studies and collected data. There were 6 studies came from 5 RCTs included in this systematic review. Compared with placebo, probiotics supplementation group had reductions in insulin (MD -4.20 IU/L (95% CI -8.11 to -0.30 IU/L), I ² = 54%) and HOMA-IR (MD -1.25 (95% CI -2.49 to -0.01), I ² = 50%). It also showed the improvements in body adiposity, lipid profile and inflammation, but they were non-significant. In addition to body adiposity and cardiovascular risk markers, there was one trail showed administration of probiotics also had an effect on iron metabolism. In conclusion, probiotics have a potential beneficial for glucose metabolism in overweight or obese postmenopausal women, but the number of current studies is small, the results need to be interpreted with caution and explained by more studies in the future.
... Since only the outcomes of BMI and BW had the required number of studies, the funnel plot test was performed solely for these outcomes using the Review Manager software from the Cochrane Collaboration. Figure 1 indicates the PRISMA flow diagram for study inclusion. Thus, 23 eligible studies were identified, including five systematic reviews [37][38][39][40][41] and 18 meta-analyses [20,24,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] (The reasons for study exclusions have been summarized in supporting file no. 1 on request). Ful-text articles excluded N= 24 Not only RCTs (2) Only abstract available (4) Data Problems (3) Not systematic review (1) Not separated Probiotics (4) Bariatric surgery or PCOS (2) Included Children or pregnant women (6) Not separated animals (1) Network-meta analysis (1) Not English (1) (Table 3). ...
... Evaluating with the AMSTAR2 tool, the results of the Metaanalysis were rated as a high level of confidence [42,43,45,51,53,[57][58][59] one as moderate [60], six as low [44,48,49,52,54,61], and three as critically low [47,50,56] as shown in (Table 2). We found four [37,38,40,41] and one [39] systematic reviews low and moderate, respectively. ...
Article
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Numerous primary and secondary studies have consistently demonstrated that probiotics, including lactobacillus and Bifidobacterium, possess a potential anti-obesity effect. However, it is worth noting that some studies have yielded contrasting results. Considering this, our study aims to present a comprehensive overview of published systematic reviews and meta-analyses, focusing on the efficacy and safety of probiotics in managing obesity. To achieve this objective, we conducted an umbrella review following the PRISMA protocol and Cochrane guidelines. We searched databases such as Embase, PubMed, Cochrane Library, and Google Scholar for relevant systematic reviews and meta-analyses published in English, without imposing any date restrictions. Our inclusion criteria encompassed studies evaluating the anti-obesity impact of probiotics, with a specific focus on changes in body mass index (BMI), fat mass percentage (FMP), body weight (BW), and body fat mass (BFM). These studies were meticulously reviewed by two independent reviewers. Our analysis included five systematic reviews and 18 meta-analyses that met the predefined inclusion and exclusion criteria. The meta-analyses revealed statistically significant reductions in the following parameters: BMI, a decrease of 0.30 kg/m² (p < 0.00001, 95% CI − 0.36 to − 0.25); BFM, a reduction of 0.86 kg (p < 0.00001, 95% CI − 1.02 to − 0.71); BW, a decrease of 0.59 kg (p < 0.00001, 95% CI − 0.74 to − 0.44); and FMP, a substantial decline of 78% (p < 0.00001, 95% CI − 1.02 to − 0.54). In summary, our umbrella review suggests that existing evidence supports the potential benefits of probiotics in managing obesity and overweight. However, it is essential to acknowledge that the credibility of this evidence is somewhat limited due to the inclusion of studies with poor-quality designs and relatively small participant numbers. To establish the true efficacy of probiotics in obesity management, we recommend conducting robust studies involving larger participant cohorts.
... In this line, the most commonly used probiotics are strains of Bifidobacterium spp. and lactic acid bacteria of the genus Lactobacillus [158,159]. Different strains of these genera have been reported to help reduce body weight, BMI, waist circumference, and fat mass in a few studies [158,159]. Improvements in some immune and metabolic markers have also been reported such as increases in high-density lipoprotein cholesterol and reductions in inflammatory proteins (C-reactive protein and MCP1) [160]. ...
... and lactic acid bacteria of the genus Lactobacillus [158,159]. Different strains of these genera have been reported to help reduce body weight, BMI, waist circumference, and fat mass in a few studies [158,159]. Improvements in some immune and metabolic markers have also been reported such as increases in high-density lipoprotein cholesterol and reductions in inflammatory proteins (C-reactive protein and MCP1) [160]. However, recent developments in sequencing techniques applied to the analysis of stool metagenomes from obese and metabolically healthy humans have revealed the potential role of new symbiotic bacterial species that may outperform traditional probiotics, representing a next generation of probiotics [161,162]. ...
Article
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Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet–microbe–host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut‐to‐brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome‐based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity‐related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.
... Waist circumference is an anthropometric indicator of the con- 46 All of the studies agree that there is a positive tendency in improving the anthropometric parameters through probiotic supplementation; however, they highlight the need for more studies to overcome the current limitations. One of the conclusions is that future clinical trials should focus on long-term therapies, given that a clear relationship has been observed between treatment duration and beneficial effects. ...
... lactis 420 and L. sakei (CJLS03) in isolation have shown consistent results toward improving the parameters related to controlling weight, including body weight, total fat mass, BMI, and waist circumference. The results also indicate that a combination of strains of the genera Bifidobacterium and Lactobacillus favor this improvement.Several recently published studies40,41,43,[46][47][48] have reported favorable results in this area. Studies have reported that the use of certain species such as Streptococcus thermophilus, Lactobacillus bulgaricus, and L. acidophilus is a valid strategy for treating excess weight and obesity.43 ...
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Background The prevalence of excess weight and obesity is increasing in an extremely concerning manner worldwide, with highly diverse therapies for current treatment. This review evaluated the scientific evidence of the past 10 years on the use of probiotics in treating excess weight and obesity in the absence of dieting. Materials A systematic review was conducted by searching for clinical trials on humans published in English in the PubMed, Scopus and Cochrane Central databases, using the combination of keywords “Overweight”, “Probiotics” and “Obesity”, and published between 2012 and 2022. Results Six published studies met the inclusion criteria. The review showed that, although there is a lack of consensus in the literature, the use of probiotics in the absence of dieting produced a significant reduction in body weight and body mass index in 66.6% of the reviewed studies, a significant reduction in waist circumference in 80.0% of the reviewed studies, and an improvement in total body fat mass and waist circumference. Conclusions This review showed evidence of a trend in preventing body weight gain and reducing weight through the use of probiotics in individuals with excess weight or obesity. A combination of various strains of the genera Bifidobacterium and Lactobacillus was the most effective.
... Therefore, BB interventions may directly impact reducing fat accumulation in certain areas, such as the abdominal region (41), which could be reflected in reductions in BFM, BFP, VFA, and WC while not significantly affecting overall BW and BMI. However, this effect could be shared for administration with mixes and isolated probiotic strains (42), representing a valuable research field for future clinical trials. ...
... Indeed, while numerous authors have addressed the direct benefits of probiotics in obesity-related outcomes (11,39,42,51,52), only a few have underscored the crucial role of the delivery matrix in probiotic products. Conventional scientific literature has often treated probiotics as independent functional components, and their delivery mode has not been given much importance in drawing experimental conclusions (49). ...
Article
This systematic review aimed to assess the impact of Bifidobacterium genus probiotics on body weight and body composition parameters in overweight and obese individuals. A systematic search for randomized controlled trials was conducted in MEDLINE, EMBASE, LILACS, and Google Scholar databases until April 17, 2023. The inclusion criteria required the trials to involve Bifidobacterium genus probiotics interventions and the evaluation of obesity-related anthropometric and body composition outcomes in overweight or obese subjects. Studies were excluded when involving obese individuals with genetic syndromes or pregnant women, as well as probiotic mixture interventions. The revised Cochrane risk-of-bias tool for randomized trials was utilized to assess the quality of the included studies. A random-effects meta-analysis was performed using the mean difference between endpoint measurements and change from baseline for body mass index, body weight, body fat mass, body fat percentage, waist circumference, waist-to-hip ratio, and visceral fat area. From 1,527 retrieved reports, 11 studies (911 subjects) were included in this review. Bifidobacterium probiotics administration resulted in significant reductions in body fat mass (MD = −0.64 kg, 95% CI: −1.09, −0.18, p = 0.006), body fat percentage (MD = −0.64%, 95% CI: −1.18, −0.11, p = 0.02), waist circumference (MD = −1.39 cm, 95% CI: −1.99, −0.79, p < 0.00001), and visceral fat area (MD = −4.38 cm 2 , 95% CI: −7.24, −1.52, p = 0.003). No significant differences were observed for body mass index, body weight, or waist-to-hip ratio. This systematic review suggests that Bifidobacterium genus probiotics may contribute to managing overweight and obesity by reducing body fat mass, body fat percentage, waist circumference, and visceral fat area. Further research is required to understand strain and species interactions, optimal dosages, and effective delivery methods for probiotics in obesity management. This review was pre-registered under the PROSPERO record CRD42022370057. KEY TEACHING POINTS • Probiotics from the Bifidobacterium genus show promise in reducing body fat mass, body fat percentage, waist circumference, and visceral fat area in overweight and obese adults. • Further research is needed to identify the most effective species and strains within the Bifidobacterium genus for achieving these outcomes. • There is an urgent need to determine the best probiotic delivery vehicle among enriched foods, capsules, or powders. • More randomized controlled trials are necessary to determine optimal probiotic doses and intervention durations.
... All these processes work together to restore a "lean gut microbiota" by modifying the composition of the gut microbiota and the metabolism of the host [77]. Recent investigations have demonstrated that probiotics can play a role in decreasing the production and accumulation of fat, as well as lowering triglyceride and cholesterol levels in the blood, also affecting the fat breakdown process [66,78]. ...
Article
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Obesity has become a global health crisis driven by genetic, environmental, and lifestyle factors, often linked to gut microbiome imbalances. Probiotics, particularly Lactobacillus and Bifidobacterium strains, have shown promise in clinical trials by promoting weight loss, improving lipid profiles, and addressing gut dysbiosis associated with obesity. This review surveys the literature on the microbiome and obesity, emphasizing the clinical relevance of probiotics in treatment strategies. Our comprehensive PubMed search highlights the mechanisms through which probiotics influence metabolic health, including their effects on inflammation and appetite regulation. We also explore promising future research directions and the potential for integrating probiotics into clinical practice. While results are encouraging, the evidence is limited by strain variability, small sample sizes, short trial durations, and individual differences in microbiota composition. More extensive, long-term studies with standardized methods are crucial to confirm the effectiveness of probiotics as viable anti-obesity treatments.
... An increase in consumer awareness of the impact of food on health has led to the rapid growth of the global probiotic food market, statistically, probiotic products now account for about 60% to 70% of the total functional food market [5][6][7]. Probiotics have been with us for as long as people have taken fermented milk, but their association with health benefits was established at the turn of the last century [8][9][10]. They can present both intestinal and nonintestinal health effects on the host [11], and are known to support or improve health by; the regulation of intestinal and respiratory microbiota [12][13][14], maintaining mucosa integrity, stimulation and development of the immune system [15], stimulation of repair mechanism of cells [13,16,17], decreasing the apoptosis of epithelial cells [18], aiding the production of antimicrobial peptides like defensing, cathelicidins bacteriocins, microcins [16], synthesizing and enhancing the bioavailability of nutrients [10,19,20], improving gut digestion by producing some extracellular enzymes, improving fat or lipid metabolism [2], reducing symptoms of lactose intolerance [10], synthesis of vitamins, predigestion of proteins and Degradation of undigested food products (cellulose or oligosaccharides) [10,[20][21][22]. ...
Article
Probiotics are live microbial dietary adjuvant that when consumed in adequate amount beneficially affects the host physiology by improving immunity and maintaining balance in the intestinal tract. Recently, awareness of the health benefits of consuming microorganisms as probiotics has increased. Probiotic foods are categorized as functional food, which are foods, or food ingredients that may provide a health benefit beyond their nutritional composition. The efficacy of probiotics largely depends on the amount consumed and the viability of the cells in the food matrix. To this effect, different types of foods were proposed as a carrier for probiotic cells, of all these foods, dairy products offer the most suitable environment for probiotic viability and growth. However, dairy-based probiotic drinks have one or two limitations in term of cost and being unsuitable for lactose intolerant individuals. Considering these limitations, other non-dairy-based food matrices such as malt-based beverages, fruit juices, cereals, vegetables, and some underutilized and under-exploited plants have been suggested as an alternative. One major challenge of using these non-dairy vehicles for delivery of probiotics is the stereotypic nature of people’s thoughts, and taste regarding dairy-based probiotics which has influenced their acceptability and consumption. This review is therefore meant to provide more information on these non-dairy based underutilized alternatives and possible ways to improve its general acceptability.
... The improvement in metabolic outcomes observed with the use of probiotics can be explained by their role in modulating glucose and lipid metabolism, determining factors for maintaining metabolic homeostasis in elderly individuals with chronic conditions. Studies suggest that probiotic supplementation can improve insulin sensitivity, reduce peripheral resistance, and promote better glycemic regulation in patients with type 2 diabetes [24]. This effect may be associated with the ability of probiotics to reduce low-grade chronic inflammation, which is one of the main characteristics of metabolic diseases [25]. ...
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Introduction: older adults, probiotic supplementation is considered promising for improving cognitive function and metabolic health, especially in conditions such as diabetes, cardiovascular disease, and hypertension. However, the extent and consistency of these effects are not yet well established in the scientific literature. In older adults, probiotic supplementation is considered promising for improving cognitive function and metabolic health, especially in conditions such as diabetes, cardiovascular disease, hypertension and neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Objective: this study aims to evaluate the cognitive and metabolic effects of probiotic use in older adults through a meta-umbrella review. Methods: a meta-umbrella review was conducted following the JBI methodology and the Reporting Guideline for Overviews of Interventions in Health (PRIOR). A systematic search was performed in databases including Web of Science, PubMed, Scopus, EMBASE, Cochrane, Epistemonikos, and CINAHL. Studies included systematic reviews and meta-analyses evaluating the cognitive and metabolic effects of probiotic supplementation in elderly individuals. Data extraction, quality assessment (using AMSTAR and ROBIS tools), and statistical analyses, including heterogeneity tests and meta-analytical synthesis, were performed. Results: from an initial pool of 287 studies, 24 systematic reviews and meta-analyses were included. The findings suggest that probiotic supplementation significantly improves cognitive function, particularly in individuals with neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease (SMD = 1.34, 95% CI: 0.51–2.16, p < 0.01). Regarding glycemic control, probiotics led to a reduction in fasting glucose levels (MD = -0.98 mmol/L, 95% CI: -1.17 to -0.78, p < 0.00001) and glycated hemoglobin (HbA1c) (MD = -0.19%, 95% CI: -0.32 to -0.07, p = 0.003). Probiotic supplementation also improved lipid metabolism by lowering total cholesterol (MD = -8.43 mg/dL, 95% CI: -12.57 to -4.28, p < 0.001) and LDL cholesterol (MD = -5.08 mg/dL, 95% CI: -7.63 to -2.53, p < 0.01), while increasing HDL cholesterol levels (MD = +1.14 mg/dL, 95% CI: 0.28–2.00, p = 0.009). Blood pressure regulation showed moderate benefits, with reductions in systolic blood pressure (MD = -3.10 mmHg, 95% CI: -5.04 to -1.16, p = 0.002) and diastolic blood pressure (MD = -1.98 mmHg, 95% CI: -3.84 to -0.12, p = 0.04). Additionally, probiotics significantly reduced inflammatory biomarkers, including C-reactive protein (CRP) (MD = -0.62 mg/L, 95% CI: -0.91 to -0.33, p < 0.001) and tumor necrosis factor-alpha (TNF-α) (MD = -0.27 pg/mL, 95% CI: -0.49 to -0.05, p = 0.02). Despite these promising findings, heterogeneity across studies was moderate to high, with I² values ranging from 40% to 85%, indicating variability in study populations, intervention durations, and probiotic strains used. Conclusion: probiotic supplementation appears to be a promising intervention for improving cognitive and metabolic health in older adults. The modulation of the gut microbiota plays a key role in regulating inflammation, energy metabolism, and neurotransmission, which may contribute to these health benefits. However, due to variations in study designs and probiotic formulations, further high-quality randomized clinical trials are needed to establish optimal strains, dosages, and treatment durations.
... The paracrine cycle involving free fatty acids and TNF-α between adipocytes and macrophages establishes a vicious cycle in obesity, exacerbating inflammatory changes in adipose tissue (Engin, 2017). Clinical studies have also shown that probiotics significantly reduce the levels of TNF-α, insulin, total cholesterol, and LDL-cholesterol in obese individuals (Pontes et al., 2021). Similarly, tangeretin administration has been shown to significantly inhibit the levels of ROS production, elastase activity, and the secretion of TNF-α, IL-6, and MCP-1 (Oh et al., 2024). ...
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Obesity, characterized by excessive body fat, is a leading preventable cause of death globally and represents one of the most critical public health challenges of the 21st century. This study aimed to investigate the action of tangeretin on gut microbiota metabolism and inflammation in high‐fat diet (HFD)‐induced obese mice. A model of obesity was established using 6‐week‐old male C57BL/6J mice fed with HFD, which were then used for the treatment with tangeretin (20 mg/kg/mice/day) or antibiotic (Abx). The results showed that the tangeretin intervention alleviated fat deposition and disorder of cellular structural integrity in the model group. The obese mice showed a significant increase in the levels of lipid (glycerol, triglyceride, and total cholesterol), inflammatory factors (IL‐6 and TNF‐α), and F4/80 expression in both serum and adipose tissues. Following tangeretin treatment, the levels of lipid, inflammatory factors, and the ratio of F4/80 + CD206 + macrophages were decreased in both serum and adipose tissue. 16S rRNA sequencing and LC‐MS/MS analysis revealed that tangeretin decreased obesity in HFD‐induced obese mice by interacting with gut microbiota, particularly influencing Parabacteroides, Blautia, and Parasutterella, and amino acids such as threonine, isoleucine, leucine, phenylalanine, arginine, glutamine, L‐tryptophan, and tyrosine. Abx‐mediated clearance of gut microbiota blocked the HFD‐induced obesity and abrogated the therapeutic effects of tangeretin in obese mice. Fecal microbiota transplantation (FMT) proved that clearing gut microbiota with Abx blocked the beneficial effects of FMTHFD+Tangeretin intervention. These findings suggested that tangeretin improved HFD‐induced obesity by regulating lipid metabolism and modulating F4/80 macrophage activation via gut microbiota.
... Previous studies have found that probiotics can influence obesity by affecting insulin sensitivity and inflammatory pathways by modulating gut microbiota compositions (19). Additionally, probiotic therapy is widely used to treat metabolic diseases, such as obesity (20,21). Current research on the use of probiotics for the treatment of obesity-related disorders has been conducted primarily using preclinical models. ...
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Obesity is a major healthcare problem worldwide and is induced by excess energy intake, resulting in gut microbial composition and microbial diversity changes. Through fermentation of dietary fibers, short-chain fatty acids (SCFAs) act as host energy sources and signaling molecules via G protein-coupled receptors such as GPR41. Acidipropionibacterium acidipropionici is widely used in many applications; however, in vivo studies on the beneficial effect of A. acidipropionici via propionate production and host energy homeostasis are unclear. Therefore, this study aimed to investigate the beneficial metabolic effects of A. acidipropionici by focusing on GPR41 signaling in a high-fat diet (HFD)-induced obesity mouse model. Here, we demonstrated that A. acidipropionici OB7439 improved host metabolism in HFD-induced obesity in mice. The intake of A. acidipropionici OB7439 improved metabolism in HFD-induced obese mice by increasing propionate production, regulating glucose tolerance, and inhibiting hepatic inflammation via GPR41 signaling. Our findings shed light on the potential of using A. acidipropionici OB7439 as an SCFA producer for the prevention and treatment of metabolic disorders. Based on these results, we suggest that A. acidipropionici may be a potential therapeutic bacterium that inhibits obesity and modulates the gut microbial community.
... This reaction results in a decrease in VCAM-1 and ICAM-1 [84]. Probiotics are "live microorganisms which when administered in adequate amounts confer a health benefit on the host" [113,114]. They reduce intestinal permeability, preventing LPS from entering the bloodstream. ...
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According to WHO (World Health Organization), in 2022, 43% of adults worldwide were overweight and 16% suffered from obesity. Overweight and obesity is a condition in which the body, due to the excess of consumed calories, accumulates it in the form of adipose tissue. However, this tissue is not only an energy store but also secretes numerous adipokines, mainly with pro-inflammatory effects. The mobilization of the immune system due to the accumulation of adipose tissue is called low-grade inflammation (LGI) and is a mediating factor between excess body weight and diseases such as cardiovascular disease, insulin resistance, type 2 diabetes, neurodegenerative diseases, sleep apnea, and even cancer. The aim of the review is to update reports related to dietary factors influencing the severity or alleviation of low-grade inflammation in obese people. The review used studies from PubMed and Google Scholar from the last 10 years. The results indicate that the Western diet, rich in processed foods, high levels of saturated fatty acids, simple sugars, salt, and low fiber and nutrient content (vitamins and minerals), leads to increased low-grade inflammation. On the other hand, calorie restrictions and an appropriate balance of macronutrients, fatty acids, and antioxidant or anti-inflammatory nutrients (e.g., polyphenols, vitamins A, C, and E, and selenium) may reduce the severity of LGI, reducing the risk of obesity-related diseases.
... While accumulating evidence supports the favorable effects of probiotics, prebiotics, and synbiotics on body adiposity (Pontes et al. 2021;Hadi et al. 2020 research on their application in childhood and adolescent obesity remains limited and controversial. Our present study systematically reviewed and quantitatively pooled data from 15 RCTs to assess the effects of supplementing probiotics, prebiotics, and synbiotics on obesity indices and cardiometabolic risk factors among children and adolescents with overweight or obesity. ...
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The efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) −2.13 kg/m2, 95% credible interval (CrI) [−2.7, −1.57]), waist circumference (MD −1.34 cm, 95% CrI [−2.33, −0.35]), total cholesterol (MD −6.55 mg/dL, 95% CrI [−10.61, −2.45]), triglycerides (MD −3.71 mg/dL, 95% CrI [−5.76, −1.67]), leptin (MD −3.99 ng/mL, 95% CrI [−4.68, −3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD −1.21 mg/L, 95% CrI [−1.45, −0.97]). Synbiotics were effective in reducing BMI-z score (MD −0.07, 95% CrI [−0.10, −0.04]) and LDL-C (MD −1.54 mg/dL, 95% CrI [−1.98, −1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings.
... However, the authors emphasized that more well-designed studies are needed, especially those taking into account specific strains of bacteria [237]. Another meta-analysis including 26 RCTs showed beneficial effects of probiotics on body weight, body fat mass, and some known risk factors of cardiovascular diseases [238]. One more study summing up 20 RCTs suggested that probiotic supplementation might contribute to lowering BMI as well as hip and waist circumference [239]. ...
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Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain–gut–microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become “block-buster” drugs due to their effectiveness in reducing body weight and beneficial effects on the patient’s metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials.
... The BMI cut-off of 30 kg/m 2 universally identifies obesity and offers significant specificity. As such, this cut-off value continues to be used as a benchmark for statistical identification and classification of obesity in reports published by the WHO, the CDC, and the NIH, as well as in many studies [1,2,86,87]. This study also used this criterion to identify obesity, with a particular emphasis on the prognostic value of SIRI and SII on all-cause and CVD mortality in this population. ...
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Aim This study aims to investigate the relationship between two novel inflammatory markers, namely, the Systemic Inflammatory Response Index (SIRI) and the Systemic Immune Inflammatory Index (SII), as well as the all-cause and cardiovascular disease (CVD) mortality in the obese population. Materials and methods We conducted a prospective cohort study based on the data of 13,026 obese adults (age ≥ 18 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and followed until December 2019. SIRI was calculated by the formula: (neutrophil count × monocyte count) / lymphocyte count, while that of SII was: (platelet count × neutrophil count)/lymphocyte count. The association of SIRI and SII with all-cause and CVD mortality was evaluated using Cox regression. In addition, the nomogram was performed to predict 10-year survival probability. Results During a median follow-up of 137 months, 1959 and 553 all-cause and CVD deaths were recorded, respectively. Spearman correlation analysis indicated that SIRI and SII were unrelated to almost all baseline characteristics (r < 0.15). Multivariate Cox regression models displayed that each standard deviation (SD) increase in SIRI was associated with a 16% (HR 1.16; 95% CI 1.09–1.24) and 22% (HR 1.22; 95% CI 1.10–1.36) increase in the risk of all-cause and CVD mortality, respectively. Likewise, every SD increase in SII was correlated with a 9% (HR 1.09; 95% CI 1.02–1.16) and 14% (HR 1.14; 95% CI 1.04–1.26) increase in the risk of all-cause and CVD mortality, respectively. The predictive value of SIRI for all-cause and CVD mortality (AUC = 0.601 and 0.624) exceeded that of SII (AUC = 0.528 and 0.539). Moreover, the nomogram displayed a substantial predictive value for 10-year survival (AUC = 0.847) with sensitivity and specificity exceeding 75%. Conclusions In the obese population, SIRI and SII are independent risk factors for all-cause and CVD mortality. Notably, the predictive ability of SIRI for both all-cause and CVD mortality significantly outperforms that of SII, suggesting that SIRI is a more valuable marker of inflammation.
... Studies have indicated that treatment targeting gut microbes can delay the progression of coronary lesions (21). Although there have been meta-analyses on the effects of probiotics on lipid metabolism, glucose metabolism, blood pressure, and inflammatory factors (22,23), they do not consider the effects of conventional drugs on the intestinal flora (24)(25)(26). Therefore, the objective of this meta-analysis was to examine the effect of probiotics on the risk factors for coronary artery lesions in conjunction with conventional drug therapy for CAD. ...
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Objective The objective of this study was to study the effect of probiotics or synbiotics on the risk factors for coronary artery disease (CAD) in the context of conventional drug therapy for CAD. Methods The literature on probiotics or synbiotics for the treatment of CAD was collected from PubMed, Scopus, Web of Science, Embase, and Cochrane Library. The search period was conducted on November 5, 2022, and the search covered all literature before November 5, 2022. The included literature consisted of randomized controlled trials of probiotics or synbiotics for CAD, and a meta-analysis was performed using Stata 14 software and RevMan 5.4 software. Results The meta-analysis explored the effect of probiotics or synbiotics on the risk factors for coronary artery lesions in a treatment setting with conventional medications for CAD. After a rigorous literature screening process, 10 studies were finally included for data consolidation to objectively evaluate the effect of probiotics or synbiotics on coronary lesions. The results of this study showed that the addition of probiotics or synbiotics to conventional medications for CAD reduced the levels of low-density lipoprotein cholesterol [weighted mean difference (WMD) −9.13 (−13.17, −5.09)], fasting glucose (FPG) [WMD −13.60 (−23.57, −3.62)], and hypersensitive C-reactive protein (hs-CRP) [standardized mean difference (SMD) −0.60 (−0.83, −0.37)] and increased the levels of high-density lipoprotein cholesterol (HDL-C) [WMD 1.94 (0.32, 3.57)], nitric oxide (NO) [WMD 5.38 (3.23, 7.54)] but did not affect the triglyceride (TG) level [WMD −13.41 (−28.03, 1.21)], systolic blood pressure (SBP) [WMD −0.88 (−3.72, 1.96)], or diastolic blood pressure (DBP) [WMD −0.21 (−2.19, 1.76)]. Conclusion Adding probiotics or synbiotics to conventional medications for CAD may improve patient prognosis. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42022362711.
... Emerging evidence suggests that probiotics have potential therapeutic effects on significant nervous system disorders such as anxiety, depression, autism, and Parkinson's disease (Lof et al., 2022). Additionally, probiotic therapy is widely used to treat metabolic diseases, such as obesity (Borgeraas et al., 2018;Pontes et al., 2021). Non-traditional studies using the microbiome and microbial-gut-brain axis as entry points for treating obesity-related cognitive impairment have been dominated by probiotic supplements, with few studies using whole fecal transfer or antibiotic treatment (Green et al., 2020). ...
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Obesity is a complex metabolic disease, with cognitive impairment being an essential complication. Gut microbiota differs markedly between individuals with and without obesity. The microbial–gut–brain axis is an important pathway through which metabolic factors, such as obesity, affect the brain. Probiotics have been shown to alleviate symptoms associated with obesity and neurobehavioral disorders. In this review, we evaluated previously published studies on the effectiveness of probiotic interventions in reducing cognitive impairment, depression, and anxiety associated with obesity or a high-fat diet. Most of the probiotics studied have beneficial health effects on obesity-induced cognitive impairment and anxiety. They positively affect immune regulation, the hypothalamic–pituitary–adrenal axis, hippocampal function, intestinal mucosa protection, and glucolipid metabolism regulation. Probiotics can influence changes in the composition of the gut microbiota and the ratio between various flora. However, probiotics should be used with caution, particularly in healthy individuals. Future research should further explore the mechanisms underlying the gut–brain axis, obesity, and cognitive function while overcoming the significant variation in study design and high risk of bias in the current evidence.
... The latter can be related to the content of the intestinal microbiota before surgery. 64 [94][95][96] It should be noted that each probiotic has different effects on body weight, gut microbiota, and glucose tolerance, respectively. It is worth considering options for the combined use of probiotics. ...
Article
Obesity has become one of modern society's most serious health problems. Studies from the last 30 years revealed a direct relationship between imbalanced energy intake and increased healthcare costs related to the treatment or management of obesity. Recent research has highlighted significant effects of gut microbial composition on obesity. We aimed to report the current knowledge on the definition, composition, and functions of intestinal microbiota. We have performed an extensive review of the literature searching for the following key words: metabolism, gut microbiota, dysbiosis, and obesity. There is evidence that an association between intestinal microbiota and obesity exists at any age. There are complex genetic, metabolic, and inflammatory mechanisms involved in the pathogenesis of obesity. Revision of indications for use of probiotics, prebiotics, and antibiotics in obese patients should be considered. Microbial composition of the gut may be an important factor involved in the development of obesity. Changes in the gut microbiota may result in changes in human metabolism and weight loss.
... They also reported a reduction in total and LDL cholesterol levels, which was not observed in our analysis. Similarly, da Silva Pontes et al. reported that probiotics reduced body weight, BMI, waist circumference, and insulin in overweight and obese subjects [22]. Probiotic supplementation has also been shown to reduce blood pressure in subjects with hypertension [23] and type 2 diabetes [24]. ...
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Background: Live dietary microbes have been hypothesized contribute to human health but direct evidence is lacking. Objectives: To determine if dietary consumption of live microbes is linked to improved health outcomes. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 were used to assess microbial intake and their adjusted associations with selected physiological parameters (e.g., blood pressure, anthropometric measures and biomarkers) among adults aged 19+ years. Regression models were constructed to assess microbial intake with each physiological parameter, adjusted for demographics and other covariates. Microbial intake was assessed as both a continuous variable and as a three-level categorical variable. Fermented foods were assessed in a separate model. Results: In continuous models, an additional 100g intake of microbe-containing foods was associated with lower systolic blood pressure -0.331 (-0.447, -0.215) mm Hg, C-reactive protein -0.013 (-0.019, -0.008) mg/dL, plasma glucose -0.347 (-0.570, -0.124) mg/dL, plasma insulin -0.201 (-0.304, -0.099) uU/mL, triglycerides -1.389 (-2.672, -0.106) mg/dL, waist circumference -0.554 (-0.679, -0.428) cm, and BMI -0.217 (-0.273, -0.160) kg/m2 and higher HDL cholesterol 0.432 (0.289, 0.574) mg/dL. Patterns were broadly similar when microbial intake was assessed categorically and when fermented foods were assessed separately. Conclusions: This study is the first to quantify, in a nationally representative data set of American adults and using stable sets of covariates in the regression models, the adjusted associations of dietary intakes of live microbes with a variety of outcomes, including anthropometric measures, biomarkers and blood pressure. Our findings suggest that foods with higher microbial concentrations are associated with modest health improvements across a range of outcomes.
... Intestinal flora can not only help the body to decompose and store fat but also regulate the immune, endocrine, metabolic, and neurological functions through immune, neuroendocrine, and vagus nerves. Therefore, the occurrence of various diseases of the human body is closely related to the disorder of intestinal flora, such as obesity [1], cardiovascular diseases [2], kidney diseases [3], and nervous system diseases [4]. ...
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Methods: We searched PubMed, Cochrane Library, and Epistemonikos to identify systematic reviews and meta-analysis (SRs). We searched for neurological diseases and psychiatric disorders, including Alzheimer's disease (AD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), anorexia nervosa (AN), bipolar disorder (BD), eating disorder (ED), generalized anxiety disorder (GAD), major depressive disorder (MDD), multiple sclerosis (MS), obsessive compulsive disorder (OCD), Parkinson's disease (PD), posttraumatic stress disorder (PTSD), spinal cord injury (SCI), schizophrenia, and stroke. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) to evaluate the quality of included SRs. We also created an evidence map showing the role of gut microbiota in neurological diseases and the certainty of the evidence. Results: In total, 42 studies were included in this evidence mapping. Most findings were obtained from observational studies. According to the AMSTAR-2 assessment, 21 SRs scored "critically low" in terms of methodological quality, 16 SR scored "low," and 5 SR scored "moderate." A total of 15 diseases have been investigated for the potential association between gut microbiome alpha diversity and disease, with the Shannon index and Simpson index being the most widely studied. A total of 12 diseases were investigated for potential link between beta diversity and disease. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia were more researched. At the genus level, Prevotella, Coprococcus, Parabacteroides, Phascolarctobacterium, Escherichia Shigella, Alistipes, Sutteralla, Veillonella, Odoribacter, Faecalibacterium, Bacteroides, Bifidobacterium, Dialister, and Blautia were more researched. Some diseases have been found to have specific flora changes, and some diseases have been found to have common intestinal microbiological changes. Conclusion: We found varied levels of evidence for the associations between gut microbiota and neurological diseases; some gut microbiota increased the risk of neurological diseases, whereas others showed evidence of benefit that gut microbiota might be promising therapeutic targets for such diseases.
... At the end of the intervention, subjects in the probiotic group showed significant reductions in plasma levels of Hcy, TNF-α, total cholesterol, LDL cholesterol, and triglycerides, and significant reductions in total antioxidant status, while subjects in the placebo group showed no significant changes in these indicators. Probiotics also improved obesity and cardiovascular risk in fat subjects, in a meta-analysis that included 26 RCTs (involving a total of 1720 overweight/obese subjects) [20]. Compared to controls, probiotic supplementation (either single or multiple bacterial species) significantly reduced subjects' body weight (-0.70 kg), BMI (-0.24 kg/m^2), waist circumference (-1.13 cm), and adiposity (-0.71 kg); probiotics had a significant reduction in obesity-related indicators only at supplemental doses ≥10^10 CFU and ≥8 weeks of intervention. ...
... Lactobacillus is a lactic acid bacterium widely found in food and in the intestinal tract, and it has both safe and effective properties [33,34], as it reduces the oxidative stress induced by higher cholesterol, and minimizes the chronic inflammation [35]. In contrast with the current finding, some studies found that some L. rhamnosus strains had the ability to lower the level of total blood lipids via different pathways, hence it competes with fatty acids in the intestine and prevents the occurrence of fatty liver [36][37][38], even though, L. rhamnosus has different strains with different beneficial modes of action, which are still under investigation. ...
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Dysbiosis is a crucial manifestation of dyslipidemia; however, oral supplementation of probiotic modulates the intestinal commensal composition. The protective mechanism of probiotics against hyperlipidemia is still under investigation. To elucidate the hypolipidemic effect of Lactobacillus rhamnosus TR08 through the analysis of gut microbiota and lipid metabolomics, we investigated changes in gut microbiota and lipid metabolomic phenotypes in mice by real time quantitative PCR and untargeted metabolomics analysis. High fat diet–induced dyslipidemia mice were orally administered with TR08 for 8 weeks. The proinflammatory cytokines (interleukin–2 and interferon–γ) levels in spleen and aortic wall injury in the mice fed with a high-fat diet were inhibited after treatment with TR08 at 1 × 10⁸ CFU per day per mouse. TR08 also reshaped the gut microbiota with increases of the relative abundances of Bifidobacterium and Bacteroides, reduced the abundance of the pro–pathogen bacterial Enterococcus, increased the serum level of short chain fatty acids (SCFAs) contents, and promoted sphingomholipid metabolic pathway. The results indicated that TR08 could improve the intestinal microbiota of mice to increase the production of SCFAs, and then play the anti–inflammation induced by hyperlipidemia and reduce the inflammatory injury of blood vessel wall. Therefore, TR08 can potentially be used as a hypolipidemic effect probiotic in further interventions.
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Background Recent evidence demonstrates the fundamental role of the gut microbiota in inflammatory diseases, and several mechanisms of action of probiotics in improvement of inflammatory parameters. Objective The objective of this review was to relate the consumption of probiotic bacteria and its effects on inflammatory diseases, including obesity, type II diabetes and celiac disease. Methods A search was carried out in English, between the years 2011 and 2022, for research articles and clinical trials with humans and in vivo studies. Research showed improvement in cardiovascular risk markers, and improvement in insulin sensitivity, lipid profile and plasma atherogenic index, in obesity with the use of probiotics. In type II diabetes, decreased levels of fasting glucose, glycated hemoglobin, insulin and glycemic index, and increased levels of peptide 1, superoxide dismutase and glutathione peroxidase were observed. Results In addition to cellular protection of the islets of Langerhans and positive alteration of TNF- α and IL-1β markers. Improvement in the condition of patients with celiac disease was observed, since the neutralization of the imbalance in serotonin levels was observed, reducing the expression of genes of interest and also, a decrease in cytokines. Conclusion Therefore, the use of probiotics should be encouraged.
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Obesity, a global epidemic, leads to metabolic dysregulation and systemic inflammation. Recently, therapies targeting the gut microbiome have garnered attention for metabolic health regulation. This study evaluates the potential of inulin‐coated medium‐chain triglyceride (InuMCT) microcapsules in rats with diet‐induced obesity (DIO). Inulin prebiotic fibers have been shown to promote the gut microbiome, while the digestion products of medium chain triglycerides (MCTs), free fatty acids, and mono‐/diglycerides, can attenuate pro‐inflammatory outcomes. It is hypothesized that encapsulating MCTs within inulin via spray drying creates a solid dosage form that can exert multifunctional effects in ameliorating inflammation in DIO. Inulin and InuMCT treatments not only reduce DIO weight gain but also improve metabolic markers in high‐fat diet (HFD) fed rats. Specifically, inulin attenuates the reduction of high‐density lipoprotein (HDL) by 55% and lowers glucose levels by 21%. Meanwhile, InuMCT increases HDL by 23% and reduces glucose levels by 15%. Furthermore, inulin decreases serum proinflammatory tumor necrosis factor‐alpha (TNF‐α) by 35%, while InuMCT further reduces TNF‐α to normal diet levels within 21 days. These results highlight InuMCT's superior efficacy, offering a promising strategy for combating obesity and related metabolic diseases.
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РЕЗЮМЕ. Проблема ожиріння стає все актуальнішою, що пояснюється збільшенням частоти цього захворювання у зв’язку із надлишковим та незбалансованим харчуванням та зменшенням фізичної активності. Мета дослідження – вивчити вплив нанокристалічного діоксиду церію на спектр жовчних кислот у жовчі щурів із змодельованим глутамат-індукованим ожирінням. Матеріал і методи. За допомогою методу тонкошарової хроматографії вивчали спектр жовчних кислот у жовчі щурів із глутамат-індукованим ожирінням та за умови корекції даної патології нанокристалічним діоксидом церію. Розраховували і аналізували зміни коефіцієнтів кон’югації та гідроксилювання жовчних кислот у півгодинних пробах жовчі, одержаних упродовж тригодинного експерименту. Результати. У щурів із глутамат-індукованим ожирінням виявлено зменшення холерезу, зростання концентрації холевої кислоти, вірогідне зниження концентрації таурохолевої і глікохолевої кислот у всіх пробах жовчі. Введення щурам нанокристалічного діоксиду церію приводить до посилення холерезу, зниження концентрації холевої кислоти та вірогідного зростання вмісту глікохолевої кислоти. Нанокристалічний діоксид церію знижує концентрацію вільних жовчних кислот у жовчі, що призводить до збільшення коефіцієнта кон’югації щодо значень у групі тварин із глутамат-індукованим ожирінням. Коефіцієнт гідроксилювання збільшується внаслідок зменшення концентрації дигідроксихоланових кислот у жовчі. Висновок. У щурів із глутамат-індукованим ожирінням виявлено зменшення холерезу та дисбаланс між жовчними кислотами: підвищення концентрації холевої кислоти (р<0,05), зниження таурохолевої (р<0,05) та глікохолевої кислоти (р<0,05), зниження концентрації сумарних таурохенодезоксихолевої та тауродезоксихолевої кислот (р<0,05). Під впливом нанокристалічного діоксиду церію у щурів із глутамат-індукованим ожирінням посилюється холерез, знижується концентрація холевої кислоти, зростає вміст глікохолевої кислоти (р<0,05), збільшуються коефіцієнт кон’югації та коефіцієнт гідроксилювання.
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This systematic review aimed to assess the impact of Bifidobacterium genus probiotics on body weight and body composition parameters in overweight and obese individuals. A systematic search for randomized controlled trials was conducted in MEDLINE, EMBASE, LILACS, and Google Scholar databases until April 17, 2023. The inclusion criteria required the trials to involve Bifidobacterium genus probiotics interventions and the evaluation of obesity-related anthropometric and body composition outcomes in overweight or obese subjects. Studies were excluded when involving obese individuals with genetic syndromes or pregnant women, as well as probiotic mixture interventions. The revised Cochrane risk-of-bias tool for randomized trials was utilized to assess the quality of the included studies. A random-effects meta-analysis was performed using the mean difference between endpoint measurements and change from baseline for body mass index, body weight, body fat mass, body fat percentage, waist circumference, waist-to-hip ratio, and visceral fat area. From 1,527 retrieved reports, 11 studies (911 subjects) were included in this review. Bifidobacterium probiotics administration resulted in significant reductions in body fat mass (MD = -0.64 kg, 95% CI: -1.09, -0.18, p = 0.006), body fat percentage (MD = -0.64%, 95% CI: -1.18, -0.11, p = 0.02), waist circumference (MD = -1.39 cm, 95% CI: -1.99, -0.79, p < 0.00001), and visceral fat area (MD = -4.38 cm2, 95% CI: -7.24, -1.52, p = 0.003). No significant differences were observed for body mass index, body weight, or waist-to-hip ratio. This systematic review suggests that Bifidobacterium genus probiotics may contribute to managing overweight and obesity by reducing body fat mass, body fat percentage, waist circumference, and visceral fat area. Further research is required to understand strain and species interactions, optimal dosages, and effective delivery methods for probiotics in obesity management. This review was pre-registered under the PROSPERO record CRD42022370057.
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Probiotics, known to be live microorganisms, have been shown to improve or restore the gut microbiota, which in turn has been linked to improved health. It is believed that probiotics are the modern equivalent of a panacea, with claims that they may treat or prevent different diseases both in children and adults (e.g., from colic in babies to cardiovascular disease, respiratory infection, and cancer in adults). Ever since the early 2000s, probiotic-based fermented foods have had a resurgence in popularity, mostly due to claims made regarding their health benefits. Fermented foods have been associated with the prevention of irritable bowel syndrome, lactose intolerance, gastroenteritis, and obesity, but also other conditions such as chronic diarrhea, allergies, dermatitis, and bacterial and viral infections, all of which are closely related to an unhealthy lifestyle. Recent and ongoing developments in microbiome/microbiota science have given us new research directions for probiotics. The new types, mechanisms, and applications studied so far, and those currently under study, have a great potential to change scientific understanding of probiotics’ nutritional applications and human health care. The expansion of fields related to the study of the microbiome and the involvement of probiotics in its improvement foreshadow an era of significant changes. An expanding range of candidate probiotic species is emerging that can address newly elucidated data-driven microbial niches and host targets. In the probiotic field, new variants of microbiome-modulating interventions are being developed, including prebiotics, symbiotics, postbiotics, microbial consortia, live biotherapeutic products, and genetically modified organisms, with renewed interest in polyphenols, fibers, and fermented foods to ensure human health. This manuscript aims to analyze recent, emerging, and anticipated trends in probiotics (sources, doses, mechanism of action, diseases for which probiotics are administered, side effects, and risks) and create a vision for the development of related areas of influence in the field.
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Obesity is a global health concern associated with a wide range of diseases, including diabetes, metabolic syndrome, fatty liver, and cardiovascular conditions. Recent studies highlight the significant role of gut microbiota in obesity. Research indicates notable changes in the composition and diversity of gut microbiota in individuals diagnosed with obesity. The gut microbiota participate in energy metabolism, lipid synthesis, and regulation of inflammation and therefore play a key role in the pathogenesis of obesity. Therapeutic approaches based on the use of probiotics, prebiotics, Akkermansia muciniphila, and fecal microbiota transplantation have shown promise in animal studies as useful strategies against obesity and metabolic syndrome. However, further research is warranted to conclusively establish the specific strains, dosages, and mechanisms underlying the effectiveness of these novel strategies against obesity in humans.
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Obesity has become a global public health problem that seriously affects the quality of life. As an important part of human diet, dairy products contain a large number of nutrients that are essential for maintaining human health, such as proteins, peptides, lipids, vitamins, and minerals. A growing number of epidemiological investigations provide strong evidence on dairy interventions for weight loss in overweight/obese populations. Therefore, this paper outlines the relationship between the consumption of different dairy products and obesity and related metabolic diseases. In addition, we dive into the mechanisms related to the regulation of glucose and lipid metabolism by functional components in dairy products and the interaction with gut microbes. Lastly, the role of dairy products on obesity of children and adolescents is revisited. We conclude that whole dairy products exert more beneficial effect than single milk constituent on alleviating obesity and that dairy matrix has important implications for metabolic health.
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Obesity is a complex chronic metabolic disease that impairs health and reduces lifespan. Therefore, effective strategies for the prevention and treatment of obesity are necessary. Although several studies have demonstrated that gut dysbiosis is associated with obesity it, remains controversial whether the altered gut microbiota is a risk factor for or a consequence of obesity. Recent randomized clinical trials (RCTs) evaluating if gut microbiota modulation with probiotics favors weight loss present conflicting results, which can be attributed to the heterogeneity in the study designs. The aim of this paper is to make a comprehensive review describing the heterogeneity of interventions and body adiposity assessment methods of RCTs that evaluated the effects of probiotics on body weight and body adiposity in individuals with overweight and obesity. Thirty-three RCTs were identified through a search strategy. As main results we observed that ∼30% of the RCTs reported a significant decrease in body weight and body mass index (BMI) and ∼50% found a significant reduction in waist circumference and total fat mass. The beneficial effects of probiotics were more consistent in trials with ≥12 weeks, probiotics dose ≥1010 CFU/day, in capsules, sachets or powder, and without concomitant energy restriction. The evidence of probiotics effects on body adiposity may improve and be more consistent in future RCTs which include methodological characteristics such as longer duration, higher dose, non-dairy vehicle, non-concurrent energy restriction and use of more accurate measures of body fat deposits (e.g., body fat mass and waist circumference) instead of body weight and BMI.
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Diet plays critical roles in defining our immune responses, microbiome, and progression of human diseases. With recent progress in sequencing and bioinformatic techniques, increasing evidence indicates the importance of diet-microbial interactions in cancer development and therapeutic outcome. Here, we focus on the epidemiological studies on diet-bacterial interactions in the colon cancer. We also review the progress of mechanistic studies using the experimental models. Finally, we discuss the limits and future directions in the research of microbiome and diet in cancer development and therapeutic outcome. Now, it is clear that microbes can influence the efficacy of cancer therapies. These research results open new possibilities for the diagnosis, prevention, and treatment of cancer. However, there are still big gaps to apply these new findings to the clinical practice.
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Objectives Pro-, pre-, and synbiotic supplements improve cardiovascular risk factors. However, the association between nonfood pro-, pre-, and synbiotics and long-term all-cause and cardiovascular mortality have not been studied. Thus, our objective was to determine the impact of nonfood pro-, pre-, and synbiotics to all-cause and cardiovascular mortality. Design, setting, and participants A retrospective, cohort study of 4837 nationally representative American participants aged 65 years or older with a median follow-up duration of 77 months. Measurements all-cause and cardiovascular mortality. Results A total of 1556 participants died during the median 77 months follow-up, and 517 died from cardiovascular disease. Compared with participants without nonfood pro-, pre-, and synbiotics use, nonfood pro-, pre-, and synbiotics use reduces nearly 41% risk of all-cause mortality (hazard ratio 0.59, 95%CI 0.43 to 0.79) and 52% risk of cardiovascular mortality (HR 0.48, 95%CI 0.30 to 0.76). Such an effect persists in most subgroup analysis and complete-case analysis. Conclusion and relevance In this study, we found a protective effect of NPPS for all-cause and cardiovascular mortality in Americans aged 65 years or older. Nonfood pro-, pre-, and synbiotics can be a novel, inexpensive, low-risk treatment addition for all-cause and cardiovascular mortality for older individuals.
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The gut microbiota encompasses a diverse community of bacteria that carry out various functions influencing the overall health of the host. These comprise nutrient metabolism, immune system regulation and natural defence against infection. The presence of certain bacteria is associated with inflammatory molecules that may bring about inflammation in various body tissues. Inflammation underlies many chronic multisystem conditions including obesity, atherosclerosis, type 2 diabetes mellitus and inflammatory bowel disease. Inflammation may be triggered by structural components of the bacteria which can result in a cascade of inflammatory pathways involving interleukins and other cytokines. Similarly, by-products of metabolic processes in bacteria, including some short-chain fatty acids, can play a role in inhibiting inflammatory processes. In this review, we aimed to provide an overview of the relationship between the gut microbiota and inflammatory molecules and to highlight relevant knowledge gaps in this field. Based on the current literature, it appears that as the gut microbiota composition differs between individuals and is contingent on a variety of factors like diet and genetics, some individuals may possess bacteria associated with pro-inflammatory effects whilst others may harbour those with anti-inflammatory effects. Recent technological advancements have allowed for better methods of characterising the gut microbiota. Further research to continually improve our understanding of the inflammatory pathways that interact with bacteria may elucidate reasons behind varying presentations of the same disease and varied responses to the same treatment in different individuals. Furthermore, it can inform clinical practice as anti-inflammatory microbes can be employed in probiotic therapies or used to identify suitable prebiotic therapies.
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Previous studies using probiotics have shown strain-dependent effects on body mass index (BMI), body mass, or fat mass (FM). The aim of this study was to evaluate how the addition of yogurt containing Lactobacillus acidophilus LA-5 and Bifidobacterium animalis subsp. lactis BB-12 strains to a diet plan affects selected anthropometric parameters in obese people on an energy-restricted diet. Fifty-four subjects aged 20–49 (34.52 ± 9.58) years were included in this study. The recruited subjects were assigned to two subgroups: consuming probiotic yogurt along with a hypocaloric diet (GP) (n–27) or the same diet but without an intentional introduction of yogurt (GRD) (n–27) for 12 weeks. Both GP and GRD decreased body weight, BMI, fat mass and visceral fat by 5.59 kg and 4.71 kg, 1.89 and 1.61 kg/m², 4.80 kg and 4.07 kg, and 0.68 and 0.65 L, respectively, although the obtained differences were not significant. Analysis of GP and GRD results separately at the beginning and end of the intervention showed that fat loss was substantial in both groups (p < 0.05). Consumption of yogurt containing LA-5 and BB-12 does not significantly improve anthropometric parameters in obese patients.
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The World Health Organization (WHO) reports that 400 million people are obese, and over 1.6 billion adults are overweight worldwide. Annually, over 2.8 million people die from obesity-related diseases. The incidence of overweight and obesity is steadily increasing, and this phenomenon is referred to as a 21st-century pandemic. The main reason for this phenomenon is an easy access to high-energy, processed foods, and a low-activity lifestyle. These changes lead to an energy imbalance and, as a consequence, to the development of body fat. Weight gain contributes to the development of heart diseases, skeletal system disorders, metabolic disorders such as diabetes, and certain types of cancer. In recent years, there have been many works linking obesity with intestinal microbiota. Experiments on germ-free animals (GFs) have provided much evidence for the contribution of bacteria to obesity. The composition of the gut microbiota (GM) changes in obese people. These changes affect the degree of energy obtained from food, the composition and secretory functions of adipose tissue, carbohydrate, and lipid metabolism in the liver, and the activity of centers in the brain. The study aimed to present the current state of knowledge about the role of intestinal microbiota in the development of obesity and the impact of supplementation with probiotic bacteria on the health of overweight and obese patients.
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Adipose tissue plays essential roles in maintaining lipid and glucose homeostasis. To date several types of adipose tissue have been identified, namely white, brown, and beige, that reside in various specific anatomical locations throughout the body. The cellular composition, secretome, and location of these adipose depots define their function in health and metabolic disease. In obesity, adipose tissue becomes dysfunctional, promoting a pro-inflammatory, hyperlipidemic and insulin resistant environment that contributes to type 2 diabetes mellitus (T2DM). Concurrently, similar features that result from adipose tissue dysfunction also promote cardiovascular disease (CVD) by mechanisms that can be augmented by T2DM. The mechanisms by which dysfunctional adipose tissue simultaneously promote T2DM and CVD, focusing on adipose tissue depot-specific adipokines, inflammatory profiles, and metabolism, will be the focus of this review. The impact that various T2DM and CVD treatment strategies have on adipose tissue function and body weight also will be discussed.
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Host-microbiota interactions involving inflammatory and metabolic pathways have been linked to the pathogenesis of multiple immune-mediated diseases and metabolic conditions like diabetes and obesity. Accumulating evidence suggests that alterations in the gut microbiome could play a role in cardiovascular disease. This review focuses on recent advances in our understanding of the interplay between diet, gut microbiota and cardiovascular disease, with emphasis on heart failure and coronary artery disease. Whereas much of the literature has focused on the circulating levels of the diet- and microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), several recent sequencing-based studies have demonstrated compositional and functional alterations in the gut microbiomes in both diseases. Some microbiota characteristics are consistent across several study cohorts, such as a decreased abundance of microbes with capacity for producing butyrate. However, the published gut microbiota studies generally lack essential covariates like diet and clinical data, are too small to capture the substantial variation in the gut microbiome, and lack parallel plasma samples, limiting the ability to translate the functional capacity of the gut microbiomes to actual function reflected by circulating microbiota-related metabolites. This review attempts to give directions for future studies in order to demonstrate clinical utility of the gut-heart axis.
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Accumulating evidence suggests obesity and its complication are linked to gut microbiota and probiotics can affect the metabolic functions of humans. The goal of this study was to systematically review the effect of probiotic and synbiotic formulations on body mass index (BMI), total body fat, waist circumstance (WC), Waist–hip ratio (WHR), and adiponectin in overweight and obese Participants in randomized trials (RCTs). A comprehensive search performed in PubMed/MEDLINE, Cochrane and SCOPUS by two researchers, independently without language or release date restrictions up to 15th October 2019. PRISMA guidelines followed to perform this meta-analysis.The inclusion criteria were: 1) RCT design, 2) intervention by pro or synbiotic, 3) Anthropometrics and/or adiponectin levels as outcome. DerSimonian and Laird random effect model used to combine results of included studies. Thirty-two studies contained 2,105 participants (n=28-200) were analyzed in this meta-analysis. Average length of intervention in included studies was 10.18 weeks and ranged from 3 to 12 weeks. Combined results showed significant reduction in BMI (WMD: -0.25 kg/m2; 95% CI -0.33, -0.17; I2=96%), total body fat (WMD: -0.75 %; 95% CI -0.90, -0.61; I2=63%), WC (WMD: -0.99 cm; 95% CI -1.33, -0.66; I2=92%), and WHR (WMD: -0.01; 95% CI -0.02, 0.01; I2=15%) in probiotic group compared to placebo. There was no significant effect on adiponectin levels by probiotic intervention (WMD: -0.01 ug/ml; 95% CI -0.33, 0.32; I2=90%). Furthermore, meta-regression showed significant relation between duration of intervention and reduction of BMI (coef=-0.1533, p<0.001) and WC (coef=-0.7131, p<0.001). The combined results showed reduction in BMI, body fat, WC, and WHR in overweight and obese patients by supplementation with probioticsor synbiotics.
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A substantial body of literature has provided evidence for the role of gut microbiota in metabolic diseases including type 2 diabetes. However, reports vary regarding the association of particular taxonomic groups with disease. In this systematic review, we focused on the potential role of different bacterial taxa affecting diabetes. We have summarized evidence from 42 human studies reporting microbial associations with disease, and have identified supporting preclinical studies or clinical trials using treatments with probiotics. Among the commonly reported findings, the genera of Bifidobacterium, Bacteroides, Faecalibacterium, Akkermansia and Roseburia were negatively associated with T2D, while the genera of Ruminococcus, Fusobacterium, and Blautia were positively associated with T2D. We also discussed potential molecular mechanisms of microbiota effects in the onset and progression of T2D.
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Nowadays, obesity is one of the most prevalent human health problems. Research from the last 30 years has clarified the role of the imbalance between energy intake and expenditure, unhealthy lifestyle, and genetic variability in the development of obesity. More recently, the composition and metabolic functions of gut microbiota have been proposed as being able to affect obesity development. Here, we will report the current knowledge on the definition, composition, and functions of intestinal microbiota. We have performed an extensive review of the literature, searching for the following keywords: metabolism, gut microbiota, dysbiosis, obesity. There is evidence for the association between gut bacteria and obesity both in infancy and in adults. There are several genetic, metabolic, and inflammatory pathophysiological mechanisms involved in the interplay between gut microbes and obesity. Microbial changes in the human gut can be considered a factor involved in obesity development in humans. The modulation of the bacterial strains in the digestive tract can help to reshape the metabolic profile in the human obese host as suggested by several data from animal and human studies. Thus, a deep revision of the evidence pertaining to the use probiotics, prebiotics, and antibiotics in obese patients is conceivable
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Obesity leads to detrimental abnormalities of iron (Fe) metabolism. So far, studies have shown that single-strain probiotic supplementation ameliorates gut microbiota quality disrupted in the obese and improves Fe homeostasis. The effect of multistrain probiotic supplementation and its dose-dependence in obese postmenopausal women remained unknown. The study aimed to investigate the effect of multistrain probiotic supplementation in two doses on selected parameters of Fe metabolism in obese postmenopausal female patients. Three groups of obese postmenopausal women, 30 subjects each, received nine-strain oral probiotic supplement in a daily dose of 2.5×109 CFU (LD group), 1×1010 CFU (HD group), or placebo for 12 weeks. ClinicalTrails.gov no.: NCT03100162. After the intervention Fe hair content was lower in both supplemented groups compared to baseline. After the intervention serum zinc (Zn) concentration was higher in LD group and lower in HD group vs. baseline. After the intervention serum erythroferrone (FAM) concentration was lower in HD group and serum ferritin (FE) concentration was higher in LD group vs. baseline. In the whole study population after the completion of the intervention hair Zn correlated positively with serum HEPC and FAM and negatively with serum FE. Hair Fe correlated negatively with serum FE. It is to conclude that multistrain probiotic supplementation may influence iron metabolism in obese postmenopausal female patients.
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Context: Recent evidence suggests that modulation of the gut microbiota may contribute to body weight control. Objective: This systematic review aimed to assess the effects of oral supplementation with probiotics or synbiotics on body weight, body mass index (BMI), and waist circumference in overweight and obese adults (BMI ≥ 25 kg/m2). Data sources: Five electronic databases-PubMed, Embase, Cochrane Library/CENTRAL, LILACS, and Web of Science-were searched from inception to August 2017. No language restrictions were applied. Study selection: Randomized and quasi-randomized parallel trials that assessed the effects of oral supplementation with probiotics or synbiotics vs any other intervention but bariatric surgery or fecal transplantation in overweight or obese adults were selected. Data extraction: Three teams of 2 authors independently assessed risk of bias and extracted data from the included trials. Data were pooled using inverse-variance random-effects meta-analyses. The quality of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Results: Nineteen randomized trials (28 publications, 1412 participants) were included. There were no differences in mean body weight change [mean difference (MD), -0.54 kg; 95%CI, -1.09 to 0.01; I2 = 0%; moderate quality of evidence) or mean BMI change (MD, -0.19 kg/m2; 95%CI, -0.43 to 0.04; I2 = 51%; low quality of evidence) between groups who received probiotics or synbiotics and control groups. Oral supplementation with probiotics or synbiotics reduced mean waist circumference compared with control (MD, -0.82 cm; 95%CI, -1.43 to -0.21; I2 = 46%; low quality of evidence). Conclusions: The findings suggest that oral supplementation with probiotics or synbiotics has a small effect to reduce waist circumference but no effect on body weight or BMI, although the quality of evidence is low to moderate. Therefore, the current evidence is not definitive. Large-scale trials are needed and may help to better inform clinical practice. Systematic review registration: PROSPERO registration number CRD42018075126.
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Microbial metabolism in the gut may alter human bile acid metabolism in a way that beneficially affects lipid homeostasis and therefore cardiovascular disease risk. Deconjugation of bile acids by microbes is thought to be key to this mechanism but has yet to be characterised in blood and stool while observing lipid markers. The aim of this study was to determine the effect of 3 different probiotic strains on plasma and stool bile acids in the context of lipid and glucose metabolism. In this 18-week, randomised, double-blind crossover study, healthy adults (53±8 years) with a high waist circumference underwent a 1-week pre-baseline period and were then randomised to receive 1 capsule/ day of Bacillus subtilis R0179 (2.5×10⁹ cfu/capsule; n=39), Lactobacillus plantarum HA-119 (5×10⁹ cfu/capsule; n=38), Bifidobacterium animalis subsp. lactis B94 (5×10⁹ cfu/capsule; n=37) or placebo for 6 weeks. Following a 3-week washout and second pre-baseline week, participants were crossed to the other intervention for 6 weeks followed by a 1-week post-intervention period. Blood and stool samples were collected at the beginning and end of each intervention to measure bile acids, serum lipid profiles, and glucose and insulin levels. Data from the placebo intervention were combined for all participants for analyses. In obese participants, the difference (final-baseline) in the sum of deconjugated plasma bile acids was greater with consumption of B. subtilis (691±378 nmol/l, P=0.01) and B. lactis (380±165 nmol/l, P=0.04) than with placebo (98±176 nmol/l, n=57). No significant differences were observed for any probiotics for stool bile acids, serum lipids, blood glucose or insulin. These data suggest that B. subtilis and B. lactis had no effect on glucose metabolism or serum cholesterol but increased deconjugated plasma bile acids in obese individuals. Additional studies should be conducted to confirm these findings and explore potential mechanisms.
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Background Coronary artery disease (CAD) is associated with gut microbiota alterations in different populations. Gut microbe-derived metabolites have been proposed as markers of major adverse cardiac events. However, the relationship between the gut microbiome and the different stages of CAD pathophysiology remains to be established by a systematic study. Results Based on multi-omic analyses (sequencing of the V3-V4 regions of the 16S rRNA gene and metabolomics) of 161 CAD patients and 40 healthy controls, we found that the composition of both the gut microbiota and metabolites changed significantly with CAD severity. We identified 29 metabolite modules that were separately classified as being positively or negatively correlated with CAD phenotypes, and the bacterial co-abundance group (CAG) with characteristic changes at different stages of CAD was represented by Roseburia, Klebsiella, Clostridium IV and Ruminococcaceae. The result revealed that certain bacteria might affect atherosclerosis by modulating the metabolic pathways of the host, such as taurine, sphingolipid and ceramide, and benzene metabolism. Moreover, a disease classifier based on differential levels of microbes and metabolites was constructed to discriminate cases from controls and was even able to distinguish stable coronary artery disease from acute coronary syndrome accurately. Conclusion Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified the relationships between the features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host–gut microbiota interplay in atherosclerotic pathogenesis. Electronic supplementary material The online version of this article (10.1186/s40168-019-0683-9) contains supplementary material, which is available to authorized users.
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Background: The prevalence of overweight/obesity in adults is raised to 39%, which is nearly tripled more than 1975. The alteration of the gut microbiome has been widely accepted as one of the main causal factors. To find an effective strategy for the prevention and treatment of overweight/obesity, a systematic review and meta-analysis were designed. Methods: In this study, we systematically reviewed the article published from January 2008 to July 2018 and conducted a meta-analysis to examine the effects of probiotics on body weight control, lipid profile, and glycemic control in healthy adults with overweight or obesity. The primary outcomes were body weight, body mass index (BMI), waist circumference, fat mass, fat percentages, plasma lipid profiles, and glucose metabolic parameters. Results: We systematically searched PubMed, Embase, and the Web of Science and identified 1248 articles, and 7 articles which were manually searched by the references of included studies and previously systematic reviews. Twelve randomized controlled trials (RCTs), including 821 participants, were included in the meta-analysis via full-text screening. Probiotics supplementation resulted in a statistical reduction in body weight (WMD [95% CI]; -0.55 [-0.91, -0.19] kg), BMI (WMD [95% CI]; -0.30 [-0.43, -0.18] kg m-2), waist circumference (WMD [95% CI]; -1.20 [-2.21, -0.19] cm), fat mass (WMD [95% CI]; -0.91 [-1.19, -0.63] kg), and fat percentage (WMD [95% CI]; -0.92 [-1.27, -0.56] %) compared with control groups. As expected, the metabolic parameters were improved significantly, with a pooled standardized mean difference in TC (SMD [95% CI]; -0.43 [-0.80, -0.07]), LDL-C (SMD [95% CI]; -0.41 [-0.77, -0.04]), FPG (SMD [95% CI]; -0.35 [-0.67, -0.02]), insulin (SMD [95% CI]; -0.44 [-0.84, -0.03]), and HOMA-IR (SMD [95% CI]; -0.51 [-0.96, -0.05]), respectively. The changes in TG (SMD [95% CI]; 0.14 [-0.23, 0.50]), HDL-C (SMD [95% CI]; -0.31 [-0.70, 0.07]), and HbA1c (SMD [95% CI]; -0.23 [-0.46, 0.01]) were not significant. Conclusion: This study suggests that the probiotics supplementation could potentially reduce the weight gain and improve some of the associated metabolic parameters, which may become an effective strategy for the prevention and treatment of obesity in adult individuals.
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Obesity is a global pandemic complex to treat due to its multifactorial pathogenesis—an unhealthy lifestyle, neuronal and hormonal mechanisms, and genetic and epigenetic factors are involved. Scientific evidence supports the idea that obesity and metabolic consequences are strongly related to changes in both the function and composition of gut microbiota, which exert an essential role in modulating energy metabolism. Modifications of gut microbiota composition have been associated with variations in body weight and body mass index. Lifestyle modifications remain as primary therapy for obesity and related metabolic disorders. New therapeutic strategies to treat/prevent obesity have been proposed, based on pre- and/or probiotic modulation of gut microbiota to mimic that found in healthy non-obese subjects. Based on human and animal studies, this review aimed to discuss mechanisms through which gut microbiota could act as a key modifier of obesity and related metabolic complications. Evidence from animal studies and human clinical trials suggesting potential beneficial effects of prebiotic and various probiotic strains on those physical, biochemical, and metabolic parameters related to obesity is presented. As a conclusion, a deeper knowledge about pre-/probiotic mechanisms of action, in combination with adequately powered, randomized controlled follow-up studies, will facilitate the clinical application and development of personalized healthcare strategies.
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Background: Obesity is a risk factor for many deadly diseases. Meanwhile, the prevalence of obesity has been continuously increasing in many countries. Probiotics are defined as live microorganisms that confer health benefits on hosts. Probiotic supplementation could reduce body weight, body mass index (BMI) and fat percentage. However, it is unclear whether supplementation with probiotics is beneficial to lower blood lipid levels for obese or overweight people. Methods: In this study, a comprehensive search across multiple databases was performed to identify studies that focused on the effects of probiotics on blood lipid levels in overweight or obese subjects. The meta-analysis included studies that compared the variations in blood lipid (total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride (TG)) concentrations between overweight and obese subjects who were supplemented with probiotics versus the controls who were not supplemented with probiotics. Results: Our findings indicated that probiotic supplementation in obese or overweight people was associated with significantly larger reductions in TC and LDL levels compared to a lack of probiotic supplementation in the control subjects. However, there was no significant difference in the variations between HDL and TG concentrations. Conclusion: Probiotic supplementation reduced TC and LDL concentrations in obese or overweight people. Additional data from large clinical trials are required to confirm the efficacy and safety of probiotics in the regulation of blood lipid levels in obese or overweight people.
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Obesity has been associated with structural and functional changes in the gut microbiota. The abundance in, and diversity of, certain bacteria may favor energy harvest and metabolic pathways leading to obesity. Therefore, gut microbiota has become a potential target that can be manipulated to obtain optimal health. Probiotics have been shown to influence the composition of the gut microbiota, improve gut integrity, and restore the microbial shifts characteristic of obesity. Based on physical and biochemical parameters, metabolic and inflammatory markers, and alterations in gut microbe diversity, animal studies revealed beneficial results in obese models whereas the results in humans are sparse and inconsistent. Thus, the purpose of this review is to present evidence from animal studies and human clinical trials demonstrating the effects of various probiotic strains and their potential efficacy in improving obesity and associated metabolic dysfunctions. Furthermore, the review discusses current gaps in our understanding of how probiotics modulate gut microflora to protect against obesity. Finally, we propose future studies and methodological approaches that may shed light on the challenges facing the scientific community in deciphering the host–bacteria interaction in obesity.
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The gut microbiota contributes to host energy metabolism, and altered gut microbiota has been associated with obesity-related metabolic disorders. We previously reported that a probiotic alone or together with a prebiotic controls body fat mass in healthy overweight or obese individuals in a randomised, double-blind, placebo controlled clinical study (ClinicalTrials.gov NCT01978691). We now aimed to investigate whether changes in the gut microbiota may be associated with the observed clinical benefits. Faecal and plasma samples were obtained from a protocol compliant subset (n=134) of participants from a larger clinical study where participants were randomised (1:1:1:1) into four groups: (1) placebo, 12 g/d microcrystalline cellulose; (2) Litesse® Ultra™ polydextrose (LU), 12 g/day; (3) Bifidobacterium animalis subsp. lactis 420™ (B420), 1010 cfu/d in 12 g microcrystalline cellulose; (4) LU+B420, 1010 cfu/d of B420 in 12 g/d LU for 6 months of intervention. The faecal microbiota composition and metabolites were assessed as exploratory outcomes at baseline, 2, 4, 6 months, and +1 month post-intervention and correlated to obesity-related clinical outcomes. Lactobacillus and Akkermansia were more abundant with B420 at the end of the intervention. LU+B420 increased Akkermansia, Christensenellaceae and Methanobrevibacter, while Paraprevotella was reduced. Christensenellaceae was consistently increased in the LU and LU+B420 groups across the intervention time points, and correlated negatively to waist-hip ratio and energy intake at baseline, and waist-area body fat mass after 6 months treatment with LU+B420. Functional metagenome predictions indicated alterations in pathways related to cellular processes and metabolism. Plasma bile acids glycocholic acid, glycoursodeoxycholic acid, and taurohyodeoxycholic acid and tauroursodeoxycholic acid were reduced in LU+B420 compared to Placebo. Consumption of B420 and its combination with LU resulted in alterations of the gut microbiota and its metabolism, and may support improved gut barrier function and obesity-related markers.
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Obesity in the postmenopausal period is associated with an increased risk of cardiovascular diseases in women. One of the key drivers of cardiovascular risk is endothelial dysfunction; thus, this is also a crucial point for studies on new therapeutic methods of cardioprotective properties. The aim of the current study was to evaluate the effect of two doses of multispecies probiotic Ecologic® Barrier supplement on functional (primary endpoint) and biochemical parameters (secondary endpoint) of endothelial dysfunction in obese postmenopausal women in a 12-week randomized, placebo-controlled clinical trial. A total of 81 obese Caucasian women participated in the trial. The subjects were randomly assigned to three groups that received a placebo, a low dose (LD) (2.5 × 109 colony forming units (CFU) per day), or a high dose (HD) (1 × 1010 CFU per day) of lyophilisate powder containing live multispecies probiotic bacteria. The probiotic supplement was administered each day for 12 weeks in two equal portions. A high dose probiotic supplementation for 12 weeks decreased systolic blood pressure, vascular endothelial growth factor, pulse wave analysis systolic pressure, pulse wave analysis pulse pressure, pulse wave analysis augmentation index, pulse wave velocity, interleukin-6, tumor necrosis factor alpha, and thrombomodulin. Low doses of probiotic supplementation decreased the systolic blood pressure and interleukin-6 levels. The mean changes in the estimated parameters, compared among the three groups, revealed significant differences in the vascular endothelial growth factor, the pulse wave analysis systolic pressure, the pulse wave analysis augmentation index, the pulse wave velocity, the tumor necrosis factor alpha, and thrombomodulin. The post hoc tests showed significant differences for all parameters between HD and the placebo group, and HD and LD (besides pulse wave analysis augmentation index). We show for the first time that supplementation with multispecies probiotic Ecologic® Barrier favorably modifies both functional and biochemical markers of vascular dysfunction in obese postmenopausal women.
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Rationale: A strong association has emerged between the gut microbiome and atherosclerotic disease. Our recent data suggest Lactobacillus plantarum 299v (Lp299v) supplementation reduces infarct size in male rats. Limited human data are available on the impact of Lp299v on the vasculature. Objective: To determine whether oral Lp299v supplementation improves vascular endothelial function and reduces systemic inflammation in humans with stable coronary artery disease (CAD). Methods and results: Twenty men with stable CAD consumed a drink containing Lp299v (20 billion CFU) once daily for 6 weeks. After a 4-week washout, subjects were given an option of additionally participating in a 10-day study of oral liquid vancomycin (250 mg QID). Vascular endothelial function was measured by brachial artery flow-mediated dilation. Before and after Lp299v, plasma short-chain fatty acids, trimethylamine oxide, and adipokine levels were measured. Additional plasma samples underwent unbiased metabolomic analyses using liquid chromatography/mass spectroscopy. 16S rRNA sequencing was used to determine changes of the stool microbiome. Arterioles from patients with CAD were obtained, and endothelium-dependent vasodilation was measured by video microscopy after intraluminal incubation with plasma from Lp299v study subjects. Lp299v supplementation improved brachial flow-mediated dilation ( P=0.008) without significant changes in plasma cholesterol profiles, fasting glucose, or body mass index. Vancomycin did not impact flow-mediated dilation. Lp299v supplementation decreased circulating levels of IL (interleukin)-8 ( P=0.01), IL-12 ( P=0.02), and leptin ( P=0.0007) but did not significantly change plasma trimethylamine oxide concentrations ( P=0.27). Plasma propionate ( P=0.004) increased, whereas acetate levels decreased ( P=0.03). Post-Lp299v plasma improved endothelium-dependent vasodilation in resistance arteries from patients with CAD ( P=0.02).16S rRNA analysis showed the Lactobacillus genus was enriched in postprobiotic stool samples without other changes. Conclusions: Lp299v improved vascular endothelial function and decreased systemic inflammation in men with CAD, independent of changes in traditional risk factors and trimethylamine oxide. Circulating gut-derived metabolites likely account for these improvements and merit further study. Clinical trial registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01952834.
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Data on the effects of probiotics on adipokines such as omentin-1, nesfatin-1, and adropin are limited. The aim of this study was to evaluate the effects of probiotic yogurt along with a low-calorie diet (LCD) on serum omentin-1, adropin, and nesfatin-1 concentrations in obese and overweight individuals. Sixty obese or overweight individuals aged 20–50 years old were involved in this randomized double-blind placebo-controlled clinical trial. Participants were randomly allocated into two groups to consume either probiotic yogurt containing Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei DN001 (10⁸ CFU/g each) (n = 30) or regular yogurt (n = 30) along with a LCD in both groups for 8 weeks. Fasting blood samples were taken at baseline and after the 8-week intervention to determine related variables. A significant decrease in body fat percentage was observed in the probiotic group compared with the regular group after 8 weeks (− 1.51 ± 069 vs − 0.88 ± 0.68%, P = 0.002). After the 8-week intervention, a significant difference in serum adropin concentration (6.04 ± 24.46 vs − 8.16 ± 24.66 pg/ml, P = 0.03 and serum omentin-1 concentration (0.09 ± 1.51 vs − 1.5 ± 1.8 ng/ml, P = 0.003) was observed between two groups. We did not observe any significant changes in nesfatin-1 and other anthropometric measures. Overall, probiotic yogurt for 8 weeks among overweight or obese individuals along with LCD had beneficial effects on body fat percentage, serum omentin-1, and adropin concentration, but it did not have any effect on nesfatin-1 level.
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A hallmark of obesity is chronic low‐grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low‐grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C‐reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low‐grade inflammation such as hsCRP and interleukin (IL)‐6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low‐grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.
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Background: One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed. Results: IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed. Conclusion: This study demonstrated that "autochthony" of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.
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During the postmenopausal period, the risk of cardiovascular diseases is increased in many obese women and is associated with a worse cardiometabolic profile and a sub-chronic low-grade systemic inflammation caused by a gut barrier permeability dysfunction. Here, we tested whether administration of two different dosages of the multispecies probiotic Ecologic ® Barrier influenced the cardiometabolic biochemical parameters and lipopolysaccharide levels, the latter used as a marker of increased gut permeability in obese postmenopausal women. A total of 81 obese Caucasian postmenopausal women participated in the trial. The subjects were randomly assigned to three groups that received a placebo, a low dose (LD) (2.5 × 10 9 colony forming units (CFU) per day), or a high dose (HD) (1 × 10 10 CFU per day) of lyophilisate powder containing live multispecies probiotic bacteria. The probiotic supplement was administered each day in two equal portions for 12 weeks. We found significant (p < 0.05) favorable changes (mostly large or medium effects) in the evaluated parameters in both the HD and LD groups but not in the placebo group. In the HD group, lipopolysaccharide, waist, fat mass, subcutaneous fat, uric acid, total cholesterol, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, and insulin-resistant index (HOMA-IR) were improved. Similar changes were observed in the LD group, except for lipopolysaccharide, uric acid, triglycerides, and glucose levels. Additionally, significant differences were observed in both groups in terms of fat percentage and visceral fat. When the mean changes were compared between the three groups, statistically significant differences in lipopolysaccharide levels, uric acid, glucose, insulin, and HOMA-IR were found. Post hoc tests revealed significant differences in the mean changes (mostly medium effects) between the HD and LD groups for uric acid, glucose, insulin, and HOMA-IR. In the 12-week randomized, placebo-controlled, double-blind intervention, we observed that supplementation with the multispecies probiotic Ecologic ® Barrier favorably affected the risk factors in a dose-dependent manner, showing beneficial effects on the cardiometabolic parameters and gut permeability of the patients. Our results suggest that this product can be effective in the prevention and treatment of cardiovascular diseases in obese postmenopausal women.
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Accumulating evidence suggests a relationship between the gut microbiota and the development of obesity, indicating the potential of probiotics as a therapeutic approach. Bifidobacterium breve B-3 has been shown to exert anti-obesity effects in high-fat diet-induced obese mice. In the present study, the anti-obesity effects of the consumption of B. breve B-3 by healthy pre-obese (25 ≤ BMI < 30) adults were investigated in a randomized, double-blind, placebo-controlled trial (trial registration: UMIN-CTR No. 000023919; preregistered on September 2, 2016). Eighty participants were randomized to receive placebo or B. breve B-3 capsules (2 × 10¹⁰ CFU/day) daily for 12 weeks. The visceral fat area significantly increased at weeks 4 and 8 in the placebo group only; no significant change was observed in the B-3 group. Body fat mass and percent body fat were significantly lower in the B-3 group than in the placebo group at weeks 8 and 12 (P<0.05, ANCOVA adjusted with baseline values). Although no significant differences were observed in blood parameters between the groups, the intake of B. breve B-3 slightly decreased triglyceride levels and improved HDL cholesterol from the baseline. No serious adverse effects were noted in either group. These results suggest that the probiotic strain B. breve B-3 has potential as a functional food ingredient to reduce body fat in healthy pre-obese individuals.
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Dietary alteration of the gut microbiome is an important target in the treatment of obesity. Animal and human studies have shown bidirectional weight modulation based on the probiotic formulation used. In this study, we systematically reviewed the literature and performed a meta-analysis to assess the impact of prebiotics, probiotics and synbiotics on body weight, body mass index (BMI) and fat mass in adult human subjects. We searched Medline (PubMed), Embase, the Cochrane Library and the Web of Science to identify 4721 articles, of which 41 were subjected to full-text screening, yielding 21 included studies with 33 study arms. Probiotic use was associated with significant decreases in BMI, weight and fat mass. Studies of subjects consuming prebiotics demonstrated a significant reduction in body weight, whereas synbiotics did not show an effect. Overall, when the utilization of gut microbiome-modulating dietary agents (prebiotic/probiotic/synbiotic) was compared to placebo, there were significant decreases in BMI, weight and fat mass. In summary, dietary agents for the modulation of the gut microbiome are essential tools in the treatment of obesity and can lead to significant decreases in BMI, weight and fat mass. Further studies are needed to identify the ideal dose and duration of supplementation and to assess the durability of this effect.
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A systematic review and meta-analysis of randomized controlled trials was conducted to examine the effects of probiotic supplementation on body weight, body mass index (BMI), fat mass and fat percentage in subjects with overweight (BMI 25-29.9 kg m À2) or obesity (BMI ≥30 kg m À2). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for studies published between 1946 and September 2016. A meta-analysis, using a random effects model, was performed to calculate the weighted mean difference between the intervention and control groups. Of 800 studies identified through the literature search, 15 were finally included. The studies comprised a total of 957 subjects (63% women), with the mean BMI being 27.6 kg m À2 and the duration of the interventions ranging from 3 to 12 weeks. Administration of probiotics resulted in a significantly larger reduction in body weight (weighted mean difference [95% confidence interval]; À0.60 [À1.19, À0.01] kg, I 2 = 49%), BMI (À0.27 [À0.45, À0.08] kg m À2 , I 2 = 57%) and fat percentage (À0.60 [À1.20, À0.01] %, I 2 = 19%), compared with placebo; however, the effect sizes were small. The effect of probiotics on fat mass was non-significant (À0.42 [À1.08, 0.23] kg, I 2 = 84%).
Chapter
This chapter details version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2), the recommended tool for use in Cochrane Reviews. The RoB 2 tool is structured into domains through which bias might be introduced into the result. The chapter summarizes the main features of RoB 2 applied to individually randomized parallel-group trials. It describes the process of undertaking an assessment using the RoB 2 tool, summarizes the important issues for each domain of bias, and deals with a list of the key differences between RoB 2 and the earlier version of the tool. The domains included in RoB 2 cover all types of bias that are currently understood to affect the results of randomized trials. These are bias arising from the randomization process; bias due to deviations from intended interventions; bias due to missing outcome data; bias in measurement of the outcome; and bias in selection of the reported result.
Chapter
A key early step in analysing results of studies of effectiveness is identifying the data type for the outcome measurements. This chapter considers outcome data of five common types: dichotomous (or binary) data, continuous data, ordinal data, count or rate data and time-to-event data. The ways in which the effect of an intervention can be assessed depend on the nature of the data being collected. For each of the types of data, the chapter reviews definitions, properties and interpretation of standard measures of intervention effect, and provides tips on how effect estimates may be computed from data likely to be reported in sources such as journal articles. Formulae to estimate effects for the commonly used effect measures are provided in a supplementary document statistical algorithms in Review Manager, as well as other standard textbooks. Effect measures are either ratio measures or difference measures. Ratio measures are typically analysed on a logarithmic scale.
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Age-related vascular endothelial dysfunction is a major antecedent to cardiovascular diseases. We investigated whether increased circulating levels of the gut microbiome-generated metabolite trimethylamine-N-oxide induces endothelial dysfunction with aging. In healthy humans, plasma trimethylamine-N-oxide was higher in middle-aged/older (64±7 years) versus young (22±2 years) adults (6.5±0.7 versus 1.6±0.2 µmol/L) and inversely related to brachial artery flow-mediated dilation (r 2 =0.29, P<0.00001). In young mice, 6 months of dietary supplementation with trimethylamine-N-oxide induced an aging-like impairment in carotid artery endothelium-dependent dilation to acetylcholine versus control feeding (peak dilation: 79±3% versus 95±3%, P<0.01). This impairment was accompanied by increased vascular nitrotyrosine, a marker of oxidative stress, and reversed by the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl. Trimethylamine-N-oxide supplementation also reduced activation of endothelial nitric oxide synthase and impaired nitric oxide-mediated dilation, as assessed with the nitric oxide synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester). Acute incubation of carotid arteries with trimethylamine-N-oxide recapitulated these events. Next, treatment with 3,3-dimethyl-1-butanol for 8 to 10 weeks to suppress trimethylamine-N-oxide selectively improved endothelium-dependent dilation in old mice to young levels (peak: 90±2%) by normalizing vascular superoxide production, restoring nitric oxide-mediated dilation, and ameliorating superoxide-related suppression of endothelium-dependent dilation. Lastly, among healthy middle-aged/older adults, higher plasma trimethylamine-N-oxide was associated with greater nitrotyrosine abundance in biopsied endothelial cells, and infusion of the antioxidant ascorbic acid restored flow-mediated dilation to young levels, indicating tonic oxidative stress-related suppression of endothelial function with higher circulating trimethylamine-N-oxide. Using multiple experimental approaches in mice and humans, we demonstrate a clear role of trimethylamine-N-oxide in promoting age-related endothelial dysfunction via oxidative stress, which may have implications for prevention of cardiovascular diseases.
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Obesity is becoming an epidemic in the United States and worldwide and increases risk for many diseases, particularly insulin resistance, type 2 diabetes mellitus, and cardiovascular disease. The mechanisms linking obesity with these diseases remain incompletely understood. Over the past 2 to 3 decades, it has been recognized that in obesity, inflammation, with increased accumulation and inflammatory polarization of immune cells, takes place in various tissues, including adipose tissue, skeletal muscle, liver, gut, pancreatic islet, and brain and may contribute to obesity-linked metabolic dysfunctions, leading to insulin resistance and type 2 diabetes mellitus. Therapies targeting inflammation have shed light on certain obesity-linked diseases, including type 2 diabetes mellitus and atherosclerotic cardiovascular disease, but remain to be tested further and confirmed in clinical trials. This review focuses on inflammation in adipose tissue and its potential role in insulin resistance associated with obesity.
Article
Abstract Purpose: Health beneficial effects of yogurt have been confirmed at the previous studies but trials on probiotic yogurt have inconsistent results. Methods: A systematically search was done to find clinical trials published in databases including PubMed, Cochrane’s library, ISI web of Science, Scopus, and Ovid from the beginning up to November 2019 to assess the effects of daily probiotic yogurt consumption on serum levels of C-reactive protein (CPR), tumor-necrosis factor-α (TNF-α), and interleukin (IL)-6. From 2193 papers, excluding duplicates, nine studies were included in this meta-analysis. Results: The pooled random-effect size analysis of nine trials showed significant effect of daily probiotic yogurt consumption on serum CRP levels [WMD (-0.26), (95% CI -0.42 to -0.09), p=0.002], but no considerable effect was seen on TNF-α [WMD (-0.32), (95% CI -2.25 to 1.6), p=0.74] and IL-6 [WMD (-0.2), (95%CI -0.53 to 0.14), p= 0.25].The subgroup analysis showed that daily probiotic yogurt consumption significantly reduced serum CRP levels in the doses lower than 200 g, for more than eight weeks in the overweight participants (25<BMI<29.9 kg/m2) with the baseline CRP levels <3 (mg/dl). Conclusions: Daily probiotic yogurt consumption for more than eight weeks showed beneficial effect on serum CRP levels in overweight people.
Article
Increased intestinal permeability has been shown to be involved in several diseases associated with low-grade chronic inflammation, including obesity and metabolic syndrome. In the last decade, growing evidence shows the beneficial effects of probiotic-containing food supplementation on these conditions. In this crossover intervention study on 28 asymptomatic overweight adults, we tested the effects of a 3-wk kefir supplementation compared with a 3-wk milk supplementation on serum zonulin levels. The effects on serum glucose, triacylglycerols, low-density lipoproteins, high-density lipoproteins, total cholesterol, markers of inflammation (C-reactive protein and adiponectin), anthropometric variables, mood, and appetite were also determined. Kefir supplementation resulted in a greater improvement of serum zonulin levels (F = 6.812, η² = 0.275), whereas a significant yet similar improvement in lipid profile and serum glucose levels was found in both supplementations. Positive mood was slightly but significantly enhanced with kefir supplementation, and reduced with milk supplementation. The C-reactive protein, adiponectin, and appetite were unaffected. In conclusion, supplementation with both dairy products had health beneficial effects, but only kefir showed an effect on the intestinal barrier dysfunction marker.
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Previous studies have recommended that probiotics may have blood pressure (BP)-lowering effects. However, they examined all probiotic strains (multi/single probiotics) simultaneously. In respect to strain specificity properties of probiotic, the aim of the present study was to systematically investigate the role of Lactobacillus plantarum as an anti-hypertensive agent by performing a meta-analysis of randomized controlled trials. PubMed, Scopus, Cochrane Library and Google Scholar were used from inception until October 2018 to identify eligible trials. We used random-effects model as the preferable method to assess the combined treatment effect. We further conducted sensitivity analysis and stratified analysis. Seven studies with 653 participants were included in the meta-analysis. The pooled weighted mean difference (WMD) with the random effects model showed a significant effects of Lactobacillus plantarum supplementation on improvement of SBP with no statistically significant heterogeneity (WMD: -1.58 mmHg, 95% CI: -3.05 to 0.11) (heterogeneity P = 0.14; I² = 36%). The overall effect in the DBP showed significant pooled estimates (WMD: -0.92 mmHg, 95% CI: -1.49 to -0.35) with a complete homogeneity between the studies (heterogeneity P = 0.46; I² = 0%). The findings of the present meta-analysis study support the use of Lactobacillus plantarum supplementation for lowering systolic and diastolic blood pressure. The clinical significance of blood pressure-lowering effect of Lactobacillus Plantarum supplementation is not considerable; however, given the overarching benefits evident and concurrent lack of specific side effects, further trials are warranted to clarify the effects of Lactobacillus Plantarum probiotics particularly for hypertensive patients.
Article
Background and aims: Potential beneficial effect of probiotic yogurt on the lipid profile has raised much interest. However, the results are inconsistent in this regard. The aim of the study is to determine the effects of probiotic yogurt on serum lipid profile in individuals with mild to moderate hypercholesterolemia. Methods and results: Online databases including PubMed, Scopus, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct, Google Scholar and Igaku Chuo Zasshi were searched until March 19th 2019. The effect sizes were expressed as the weighted mean difference (WMD) with 95% confidence interval (CI). Seven eligible trials with 274 participants were included in this systematic review. Pooling of 9 effect sizes from these seven articles revealed a significant reduction in total cholesterol and low density lipoprotein cholesterol levels following probiotic yogurt consumption (mean difference: -8.73 mg/dl, 95% CI: -15.98, -1.48, p-value = 0.018 and mean difference: -10.611 mg/dl, 95% CI: -16.529, -4.693, p-value = 0.000, respectively) without significant heterogeneity among the studies (I2 = 40.6%, p-value = 0.1 and I2 = 24.2%, p-value = 0.229, respectively). The results showed no significant changes in high density lipoprotein cholesterol and triglyceride levels. Also, none of the variables showed a significant change for sensitivity analysis. Conclusion: Available evidence suggests that probiotic yogurt can significantly reduce total cholesterol and LDL-c in subjects with mild to moderate hypercholesterolemia without a significant effect on HDL-c and triglyceride levels.
Article
Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease. Emerging evidence indicates that these disorders are characterized by alterations in the intestinal microbiota composition and its metabolites, which translocate from the gut across a disrupted intestinal barrier to affect various metabolic organs, such as the liver and adipose tissue, thereby contributing to metabolic inflammation. Here, we discuss some of the recently identified mechanisms that showcase the role of the intestinal microbiota and barrier dysfunction in metabolic inflammation. We propose a concept by which the gut microbiota fuels metabolic inflammation and dysregulation. Here, the authors describe how metabolic disorders, such as type 2 diabetes and nonalcoholic fatty liver disease, are driven by alterations in the composition of the intestinal microbiota and its metabolites, which translocate from the gut across a disrupted intestinal barrier and contribute to metabolic inflammation.
Article
Animal models support a role for the gut microbiota in the development of hypertension. There has been a lack of epidemiological cohort studies to confirm these findings in human populations. We examined cross-sectional associations between measures of gut microbial diversity and taxonomic composition and blood pressure (BP) in 529 participants of the biracial (black and white) CARDIA study (Coronary Artery Risk Development in Young Adults). We sequenced V3-V4 regions of the 16S ribosomal RNA marker gene using DNA extracted from stool samples collected at CARDIA's Year 30 follow-up examination (2015-2016; aged 48-60 years). We quantified associations between BP (hypertension [defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg or antihypertension medication use] and systolic BP) and within and between-person diversity measures. We conducted genera-specific multivariable-adjusted regression analysis, accounting for multiple comparisons using the false discovery rate. Hypertension and systolic BP were inversely associated with measures of α-diversity, including richness and the Shannon Diversity Index, and were distinguished with respect to principal coordinates based on a similarity matrix of genera abundance. Several specific genera were significantly associated with hypertension and systolic BP, though results were attenuated with adjustment for body mass index. Our findings support associations between within-person and between-person gut microbial community diversity and taxonomic composition and BP in a diverse population-based cohort of middle-aged adults. Future study is needed to define functional pathways that underlie observed associations and identify specific microbial targets for intervention.
Article
This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut–liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.
Article
Objectives: The relationship between gut microflora and metabolic syndrome components such as obesity, low-grade chronic systemic inflammation, dyslipidemia, and altered glucose metabolism is now acknowledged. The aim of this study was to assess the effects of probiotic yogurt on glycemic indexes and endothelial dysfunction markers in patients with metabolic syndrome. Methods: This was a randomized, double-blind, placebo-controlled clinical trial of 44 patients with metabolic syndrome (22 men and 22 women), who were 20 to 65 y of age. The patients were assigned to either a treatment or control group and consumed 300g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or a regular yogurt for 2 mo, respectively. Each group contained 22 participants. Fasting blood glucose and serum insulin was performed to derive homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity (Quicki), and HOMA of β-cell function (HOMA- β). In addition, markers of vascular cell adhesion molecule cell (VCAM)-1, intercellular adhesion molecule cell (ICAM)-1, and plasminogen activator inhibitor (PAI)-1 were measured to evaluate endothelial function at the beginning and at the end of the study. Results: Consumption of probiotic yogurt resulted in a significant reduction in the level of blood glucose and VCAM-1. Significant changes in PAI-1, VCAM-1, insulin, HOMA-IR, and Quicki were observed in the probiotic yogurt group after intervention compared with baseline. Conclusion: Consumption of probiotic yogurt improved fasting blood glucose and partly modified serum endothelial function markers. These results suggest that regular intake of probiotic yogurt may exert positive effects on the treatment of metabolic syndrome.
Article
Lactobacillus gasseri BNR17 is a probiotic strain isolated from human breast milk. Animal studies reported that BNR17 inhibited increases in body weight and adipose tissue weights. The purpose of this study was to evaluate the antiobesity effects of BNR17 in humans. In a randomized, double-blind, placebo-controlled trial, 90 volunteers aged 20-75 years with body mass index (BMI) from 25 to 35 kg/m2 were randomized to receive a placebo, low-dose BNR (BNR-L, 109 CFU/day), or high-dose BNR (BNR-H, 1010 CFU/day) for 12 weeks. Body weight, BMI, waist and hip circumferences, waist-to-hip ratio, abdominal adipose tissue areas, body fat mass, lean body mass, and biochemical parameters were assessed at the beginning and end of the trial. Visceral adipose tissue (VAT) was significantly decreased in the BNR-H group compared with the placebo group (P = .038). Difference of VAT areas of the BNR-H group compared with the placebo group after 12-week consumption of BNR17 was significant (-21.6 cm2, P = .012). Waist circumferences were significantly decreased in both the BNR-L and BNL-H groups (P = .045 and .012, respectively) compared with the baseline values, but not in the placebo group. Biochemical parameters were not significantly different among the groups. These findings suggest that daily consumption of BNR17 may contribute to reduced visceral fat mass in obese adults.
Article
Microbial communities are associated with the human host, primarily in the intestinal tract, where they affect host metabolism and contribute to the pathogenesis of cardiovascular disease. The susceptibility to atherosclerosis and thrombosis can be transmitted via gut microbial transplantation in mouse models. Microbial-associated molecular patterns are sensed by host pattern recognition receptors and affect cardiovascular disease pathogenesis. Microbial metabolism of common dietary nutrients produces both anti-atherogenic and pro-atherogenic metabolites that engage distinct host receptor systems and affect cardiovascular disease pathogenesis. Plasma levels of the gut microbial metabolite trimethylamine-N-oxide are associated with incident development of cardiovascular disease and its adverse outcomes in humans. Bacterially derived short-chain fatty acids (acetate, propionate and butyrate) can engage host receptor systems and potentially affect cardiovascular pathogenesis. Bacterially derived secondary bile acids can modulate dietary fat absorption and signal through cell-surface and nuclear hormone receptors, potentially affecting cardiovascular disease pathogenesis. Gut microorganism-targeted therapeutic strategies hold promise for the prevention and/or treatment of cardiovascular disease.
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p>The gut microbiota has been associated with many different disorders, including cardiovascular diseases. A new study by Jie and colleagues is the first large case–control study to examine directly the enrichment of certain communities of gut bacteria in patients with atherosclerotic cardiovascular disease compared with control individuals.</p