ArticleLiterature Review

Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota

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Abstract

Obesity and associated metabolic disorders are worldwide epidemic. The literature provides new evidence that gut microbiota dysbiosis (at the phyla, genus, or species level) affects host metabolism and energy storage. Here we discuss new findings that may explain how gut microbiota can be involved in the development or in the control of obesity and associated low-grade inflammation. New powerful molecular biology methods and the use of gnotobiotic animal allowed to analyze the molecular link between gut bacteria and the host. Moreover, even if more studies are needed to unravel how changing gut microbiota impacts on the development of obesity and related metabolic alterations, probiotic and prebiotic approach appear as potential interesting treatments to reverse host metabolic alterations linked to gut microbiota dysbiosis.

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... besity is a global health problem due to change in people's life style. Various factors, including genetic and environmental factors, are involved in the pathophysiology of obesity [1][2][3] . Gut microbiota has been known as an important environmental factor for inducing and developing obesity. ...
... Therefore, any change in gut microbiota composition, which is termed dysbiosis, can lead to disruption in host functions and development of metabolic disorders, including obesity and type 2 diabetes . In this regard, determination of altered gut microbiota composition is an inevitable part of etiological recognition of obesity [2,9,10] . ...
... Obesity is associated with low-grade inflammation, insulin resistance, increased weight gain, and fat deposition [2,11] . It has been documented that high-fat diet induces dysbiosis, which favors the increase of energy harvest from diet, deregulation of immune responses, and metabolic pathways [1,2,12] . ...
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Background: Obesity is a complex disorder influenced by various genetic and environmental factors. It has been shown that gut microbiota, which colonizes gastrointestinal tract, has a substantial role as an environmental factor in the pathophysiology of obesity. Since the composition of gut microbiota alters with regard to different criteria, such as ethnicity, geographical location, diet, lifestyle, age, and gender, we aimed to determine firmicutes/bacteroidetes (F/B) ratio and the abundance of important gut microbiota members, Akkermansia muciniphila, Faecalibacterium prausnitzii, Roseburia, Bifidobacterium, and Prevotella in Iranian obese and normal weight individuals, for the first time. Methods: In this study, 50 normal and 50 obese subjects were recruited and classified based on their body mass index into normal weight and obese groups. Stool samples were collected. Following DNA extraction from the samples, quantitative PCR was conducted based on 16s rDNA universal primers. Finally, the correlation between the bacterial abundance and obesity was analyzed by statistical analyses. Results: We observed a significant increase of F/B ratio in the obese group, compared to the normal weight group (p = 0.002). Although A. muciniphila (p = 0.039) and Bifidobacterium (p = 0.049) abundance significantly decreased, the abundance of F. prausnitzii (p = 0.046) significantly elevated with BMI increase in the studied groups. Conclusion: Owing to the importance of the gut microbiota composition in obesity development, determination and targeted restoration of gut microbiota pattern could be valuable in the control and treatment of obesity in certain populations.
... These aging phenotypes are similar to HFD-induced in ammation and obesity. A HFD alters gut microbial composition and increases intestinal permeability, which leads to colonic low-grade in ammation and an increase in endotoxin levels in the intestinal lumen as well as in the plasma [56,57]. Excessive amounts of endotoxin are correlated with gut, hepatic, and adipose tissue in ammation and diabetes [56,57]. ...
... A HFD alters gut microbial composition and increases intestinal permeability, which leads to colonic low-grade in ammation and an increase in endotoxin levels in the intestinal lumen as well as in the plasma [56,57]. Excessive amounts of endotoxin are correlated with gut, hepatic, and adipose tissue in ammation and diabetes [56,57]. ...
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Background: Aging is a progressive decline of cellular functions that ultimately affects whole-body homeostasis. Alterations in the gut microbiota associated with aging have been reported, however the molecular basis of the relationships between host aging and the gut microbiota is poorly understood. Result: By using longitudinal microbiome and metabolome characterization, we show that the aging-related alterations in the intestinal environment lead to gut dysbiosis with a potential to induce obesity in mice. In middle-age mice, we observed more than a 2-fold increase in fecal carbohydrates derived from dietary polysaccharides and a significant reduction of gut microbial diversity resembling the microbiota characteristic of obese mice. Consistently, fecal microbiota transplantation from middle-age specific pathogen-free (SPF) mice into young germ-free (GF) mice resulted in increased weight gain and impaired glucose tolerance. Conclusion: Our findings provide new insights into the relationships between host aging and gut dysbiosis and may contribute to the development of a possible solution to aging-related obesity.
... There is mounting scientific evidence for the association of the gut microbiota with beneficial effects of probiotics on obesity and related metabolic diseases [22][23][24]. Examples Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12602-020-09672-5) contains supplementary material, which is available to authorized users. ...
... include the administration of probiotics foe effectively reducing reduce weight gain, increasing insulin sensitivity, regulating inflammation, and modulating the gut microbiome through the decrease in the ratio of Firmicutes/Bacteroidetes within the host in high fat-induced murine models and clinical studies [22][23][24]. Although the exact mechanisms of probiotic functions are still quite unclear and different mechanisms were proposed and investigated, research findings suggest and confirm a shift in the population and changes in the diversity of the gut microbiota beneficially impacting host physiology [25,26]. ...
Article
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Unveiling and understanding differences in physiological features below the species level may serve as an essential fast-screening tool for selecting strains that can promote a specific probiotic effect. To study the intra-species diversity of Bacillus, a genus with a wide range of enzyme activities and specificity, 190 Bacillus strains were isolated from traditional Korean fermented food products. Altogether, in the preliminary safety screening, 8 of these strains were found negative for lecithinase and hemolysis activity and were selected for further investigations. On the basis of different levels of enzyme functionalities (high or low proteolytic, amylolytic, and lipolytic (PAL) activities), two Bacillus subtilis strains were selected for an in vivo study. Each of the two strains was separately administered at a level of 1 × 108 CFU per day to C57BL/6 mice that were fed 60% high-fat diet ad libitum for 8 weeks, while Xenical, an anti-obesity drug, was used as a positive control in the experimental setup. B. subtilis M34 and B. subtilis GS40a with low and high amylolytic activities, respectively, induced significantly different and contrasting physiological effects. The production of short-chain fatty acids appeared to be closely associated with a shift in the gut microbiota.
... Metabolites with a potential bacterial origin are also among the top contributors to models and the most significantly associated with MetS. The gut microbiome has been reported as being able to influence susceptibility to obesity by altering the efficiency of energy harvest from the diet [20]. On the other hand, the gut bacterial ecosystem and the corresponding bacterial co-metabolism are altered by obesity and can promote low-grade inflammation and metabolic disease [20]. ...
... The gut microbiome has been reported as being able to influence susceptibility to obesity by altering the efficiency of energy harvest from the diet [20]. On the other hand, the gut bacterial ecosystem and the corresponding bacterial co-metabolism are altered by obesity and can promote low-grade inflammation and metabolic disease [20]. Some studies suggest that metabolites in the pathways from choline to trimethylamines are indicative of the gut microbiota status [21]. ...
Article
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Adult morbid obesity is defined as abnormal or excessive fat accumulation, mostly resulting from a long-term unhealthy lifestyle. Between 10% and 30% of people with obesity exhibit low cardiometabolic risk. The metabolic syndrome has been suggested as an indicator of obesity-related metabolic dysregulation. Although the prevalence of obesity does not seem to be sex-related and metabolic syndrome occurs at all ages, in the last few years, sex-specific differences in the pathophysiology, diagnosis, and treatment of metabolic syndrome have received attention. The aim of this study was to determine the prevalence of metabolic syndrome and its components in different sex and age groups in people with metabolic unhealthy obesity and to compare them with people with metabolic healthy obesity. We analyzed the metabolome in 1350 well-phenotyped morbidly obese individuals and showed that there is a strong sex-dependent association of metabolic syndrome with circulating metabolites. Importantly, we demonstrated that metabolic dysregulation in women and men with severe obesity and metabolic syndrome is age-dependent. The metabolic profiles from our study showed age-dependent sex differences in the impact of MetS which are consistent with the cardiometabolic characterization. Although there is common ground for MetS in the metabolome of severe obesity, men older than 54 are affected in a more extensive and intensive manner. These findings strongly argue for more studies aimed at unraveling the mechanisms that underlie this sex-specific metabolic dysregulation in severe obesity. Moreover, these findings suggest that women and men might benefit from differential sex and age specific interventions to prevent the adverse cardiometabolic effects of severe obesity.
... Recent scientific data have linked MetS development also to intestinal dysbiosis [5,6]: because of increased intestinal permeability, the translocation of lipopolysaccharide (LPS), an outer membrane component of Gram-negative bacteria, occurs, thus determining metabolic endotoxemia, which can be viewed as a causal factor of chronic low-grade systemic inflammation [7,8]. ...
... Systemic LPS concentration is significantly elevated in NAFLD compared to control groups, in both human and animal studies [68][69][70][71]. The gut microbiota contributes to liver fat deposition through modulation of the nuclear farnesoid X receptor (FXR), responsible for regulation of bile acid synthesis, and hepatic triglyceride accumulation [8,11,55]. After a meal, primary bile acids (chenodeoxycholic and cholic acids), stored in the gall bladder, are secreted in the duodenum, where they can be deconjugated by gut microbes, thus being metabolized into secondary bile acids in the colon [72]. ...
Article
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Metabolic syndrome (MetS) is a complex pathophysiological state with incidence similar to that of a global epidemic and represents a risk factor for the onset of chronic non-communicable degenerative diseases (NCDDs), including cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and some types of cancer. A plethora of literature data suggest the potential role of gut microbiota in interfering with the host metabolism, thus influencing several MetS risk factors. Perturbation of the gut microbiota’s composition and activity, a condition known as dysbiosis, is involved in the etiopathogenesis of multiple chronic diseases. Recent studies have shown that some micro-organism-derived metabolites (including trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS) of Gram-negative bacteria, indoxyl sulfate and p-cresol sulfate) induce subclinical inflammatory processes involved in MetS. Gut microbiota’s taxonomic species or abundance are modified by many factors, including diet, lifestyle and medications. The main purpose of this review is to highlight the correlation between different dietary strategies and changes in gut microbiota metabolites. We mainly focus on the validity/inadequacy of specific dietary patterns to reduce inflammatory processes, including leaky gut and subsequent endotoxemia. We also describe the chance of probiotic supplementation to interact with the immune system and limit negative consequences associated with MetS.
... Metabolic endotoxemia, which is defined as a 2-3 times increase in circulating endotoxin (5), is an early etiological factor in MetS that initiates insulin resistance and obesity (6). Endotoxemia results from the excess absorption of gut-derived endotoxins (e.g., LPS derived from the membrane of Gram-negative bacteria) (6,7). Although transcellular chylomicron-mediated absorption of endotoxin helps to limit its proinflammatory effects, paracellular absorption of endotoxin resulting from "leaky gut" is highly implicated in cardiometabolic risk (8). ...
... This planned controlled trial will therefore address several knowledge gaps relating to MFGM, and more broadly full-fat dairy milk, that can support evidence-based dietary recommendations that supersede those that are largely based on outcomes of observational studies. Such findings are important for advancing an understanding of the health benefits of dairy foods but also for health conditions such as MetS in which metabolic endotoxemia is implicated (6,7,9,11). ...
Article
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Background: Milk fat globule membrane (MFGM) is a phospholipid-rich component of dairy fat that might explain the benefits of full-fat dairy products on cardiometabolic risk. Preclinical studies support that MFGM decreases gut permeability, which could attenuate gut-derived endotoxin translocation and consequent inflammatory responses that impair cardiometabolic health. Objectives: To describe the rationale, study design, and planned outcomes that will evaluate the efficacy of MFGM-enriched milk compared with a comparator beverage on health-promoting gut barrier functions in persons with metabolic syndrome (MetS). Methods: We plan a double-blind, randomized, crossover trial in which people with MetS will receive a rigorously controlled eucaloric diet for 2 wk that contains 3 daily servings of an MFGM-enriched bovine milk beverage or a comparator beverage that is formulated with nonfat dairy powder, coconut and palm oils, and soy phospholipids. Compliance will be monitored by assessing urinary para-aminobenzoic acid that is added to all test beverages. After the intervention, participants will ingest a high-fat/high-carbohydrate meal challenge to assess metabolic excursions at 30-min intervals for 3 h. Nondigestible sugar probes also will be ingested prior to collecting 24-h urine to assess region-specific gut permeability. Intervention efficacy will be determined based on circulating endotoxin (primary outcome) and glycemia (secondary outcome). Tertiary outcomes include: gut and systemic inflammatory responses, microbiota composition and SCFAs, gut permeability, and circulating insulin and incretins. Expected results: MFGM is expected to decrease circulating endotoxin and glycemia without altering body mass. These improvements are anticipated to be accompanied by decreased gut permeability, decreased intestinal and circulating biomarkers of inflammation, increased circulating incretins, and beneficial antimicrobial and prebiotic effects in the gut microbiome. Conclusions: Demonstration of improvements in gut barrier functions that limit endotoxemia and glycemia could help to establish direct evidence that full-fat dairy lowers cardiometabolic risk, especially in people with MetS.The clinical trial associated with this article has been registered at clinicaltrials.gov (NCT03860584).
... Indeed, many researchers have underlined the role of gut microbiota for host health. Furthermore, the gut microbiota has emerged as an important environmental factor for metabolic disease including obesity and type 2 diabetes mellitus [6,12,13]. Most of these studies have focused on the metabolites produced by bacteria (e.g., shortchain fatty acids [SCFAs] and bile acids) and the signaling pathways that can affect host energy metabolism. ...
... Diet composition is also highly linked with the proportion of gut microbiota and the diet source can directly change gut microbiota composition in human [68,69], and the altered microbiota contribute Diabetes Metab J 2020 Forthcoming. Posted online 2020 https://e-dmj.org to an enhanced harvest of energy from the hosts diet in patients with obesity and metabolic diseases [12,70]. ...
Article
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Over a hundred billion bacteria are found in human intestines. This has emerged as an environmental factor in metabolic diseases, such as obesity and related diseases. The majority of these bacteria belong to two dominant phyla, Bacteroidetes and Firmicutes. Since the ratio of Firmicutes to Bacteroidetes increases in people with obesity and in various animal models, it has been assumed that phylum composition causes the increase in occurrence of metabolic diseases over the past decade. However, this assumption has been challenged by recent studies that have found even an opposite association of phylum composition within metabolic diseases. Moreover, the gut microbiota affects host energy metabolism in various ways including production of metabolites and interaction with host intestinal cells to regulate signaling pathways that affect energy metabolism. However, the direct effect of gut bacteria on host energy intake, such as energy consumption by the bacteria itself and its effects on intestinal energy absorption, has been underestimated. This review aims to discuss whether increased ratio of Firmicutes to Bacteroidetes is associated with the development of metabolic diseases, and whether energy competition between the bacteria and host is a missing part of the mechanism linking gut microbiota to metabolic diseases.
... Literatures have suggested that occurrence of obesity and its comorbidities are not solely due to the changes in the host genome or sedentary lifestyle or consumption of more energy than expended. Changes in gut microbiota (dysbiosis) are also considered as one of the reasons for the development of obesity (Cani and Delzenne 2009). However, the role of gut microbiota in metabolic disorders is still controversial and debatable. ...
Chapter
Enzymes are biocatalysts which have a central role in the biochemical, physiological, and metabolic functioning of all the organisms from micro to macro level. These catalytic proteins or metalloproteins have wonderful applications in a number of processes for conversion of substrates to useful products and are used in pharmaceutical, nutraceutical, cosmetic, food and beverage, and other industries. Different sources of these enzymes have been explored for commercial production. The reservoir of microbial world has not been investigated to a greater extent. The microorganisms have proved as an effective source of these industrially important enzymes. The reason for exploring enzymes from microorganisms is their stability at different physiological conditions like high and low temperature, pH, salinity, and others like high catalytic activity and ease of standardization and production. In recent times, the enhancement of production of these microbial enzymes can be achieved using different genetic modulatory methodologies, physiological parameter redesigning, and protein bioengineering. These techniques are the focus of researchers for industrial-friendly hyperproduction of microbial enzymes for generating various formulations.
... Literatures have suggested that occurrence of obesity and its comorbidities are not solely due to the changes in the host genome or sedentary lifestyle or consumption of more energy than expended. Changes in gut microbiota (dysbiosis) are also considered as one of the reasons for the development of obesity (Cani and Delzenne 2009). However, the role of gut microbiota in metabolic disorders is still controversial and debatable. ...
Chapter
Consumption of probiotics in the form of fermented products has a long history. Since the last two decades, probiotics has gained the attention of the scientific community because of their health beneficial effects. Positive effects of probiotics on metabolic disorders such as nonalcoholic fatty liver disease, immune diseases, obesity, diabetes, insulin resistance, cardiovascular disease, irritable bowel syndrome, and inflammatory bowel disease have been reported, but exact mechanism of action of probiotics in amelioration of these disorders is yet to be elucidated. Generally, genera Lactobacillus and Bifidobacterium are employed as probiotics. Different probiotics act differently in conferring health beneficial effects. Moreover, health-promoting effects of probiotics are dependent on the strain. Furthermore, probiotic dosages, feeding schedule, mechanism of action, and long-term effects on health are yet to be elucidated. Therefore, further studies are required to explain the health beneficial effects of probiotics before it can be rationally prescribed to patients. In this chapter, we will discuss about role of probiotics in the prevention and treatment of various metabolic disorders.
... Since scientists have found that the composition of the gut microbiota is significantly different between the lean mice and the obese mice, the latter showing lower Bacteroidetes and higher Firmicutes bacteria (Ley et al., 2005) levels, people began to realize the close connection between the gut microbiota and obesity. Subsequently, the gut microbiota has been found not only responsible for the weight gain and energy harvest (Samuel et al., 2008), but also involved in the development of the low-grade inflammation associated with obesity (Cani and Delzenne, 2009). ...
Article
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Gut microbiota, an integral part of the human body, comprise bacteria, fungi, archaea, and protozoa. There is consensus that the disruption of the gut microbiota (termed “gut dysbiosis”) is influenced by host genetics, diet, antibiotics, and inflammation, and it is closely linked to the pathogenesis of inflammatory diseases, such as obesity and inflammatory bowel disease (IBD). Macrophages are the key players in the maintenance of tissue homeostasis by eliminating invading pathogens and exhibit extreme plasticity of their phenotypes, such as M1 or M2, which have been demonstrated to exert pro- and anti-inflammatory functions. Microbiota-derived metabolites, short-chain fatty acids (SCFAs) and Gram-negative bacterial lipopolysaccharides (LPS), exert anti-inflammatory or pro-inflammatory effects by acting on macrophages. Understanding the role of macrophages in gut microbiota-inflammation interactions might provide us a novel method for preventing and treating inflammatory diseases. In this review, we summarize the recent research on the relationship between gut microbiota and inflammation and discuss the important role of macrophages in this context.
... Collective genomes of gut microbes are called gut microbiome. Gut microbiota, consisted of trillions of microorganisms and modulated mainly by diet (Scott et al., 2012), has recently been recognized as a primary mediator for human health (Cani & Delzenne, 2009;Everard & Cani, 2013). The gut microbiome, which may contain > 100 times the number of genes in our genome, endows us with functional features that we have not had to evolve ourselves (Bäckhed et al, 2005). ...
Article
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The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut. The association of the gut microbiota with human health and disease has been widely studied. A number of human disorders and diseases have been directly and indirectly associated with the microbiome. Children with Autism Spectrum Disorder (ASD) have distinctive gut microbiota compared to neurotypical children. Autism spectrum disorder (ASD) is associated with several oropharyngeal abnormalities, including dysbiosis in the oral microbiota. As there is a correlation between abnormal microbiota and development of autism like behaviour, so, modifying the gut microbiome by probiotics, prebiotics, antibiotics and fecal microbiota transplant (FMT) could be a potential route to improve GI and behavioural symptoms in children with ASD.
... Excessive inflammation results in loss of epithelial integrity, which in turn leads to further bacterial translocation and thus further induction of inflammation [8,24]. This condition is observed in a number of gastrointestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC) [26], central nervous system disorders such as depression and schizophrenia [27], obesity [28], diabetes mellitus [29], cardiovascular disorders [30], rheumatoid arthritis [31] and multiple sclerosis [24], and asthma and atopy in children [32]. Research found that Faecalibacterium prausnitzii is reduced in patients with ulcerative colitis, another chronic inflammatory condition of the colon [33]. ...
Article
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Our gut harbours around 1014bacteria of more than 1000 species, accounting for approximately 2 kg of biomass. Thegut microbiome plays several vital functions in processes such as the development of the immune system, food digestion and protection against pathogens. For these functions to be beneficial for both host and microbiome, interactions are tightly regulated.Gut and immune cells continuously interact to distinguish among commensal microbiota, harmless foodstuff, and pathogens. A fine balance between inflammatory and anti-inflammatory state is fundamental to protect intestinal homeostasis. Nonsteroidal anti-inflammatories (NSAIDs) are a class of drugs used for management of pain and inflammation. These compounds have heterologous structures but similar therapeutic activities. The target of all NSAIDs are the isoforms of cyclooxygenase enzymes (COX): the primarily constitutive form COX-1, and the inducible from COX-2. Both isoforms catalyse the conversion of arachidonic acid to PGH2, the immediate substrate for specific prostaglandin and thromboxane synthesis. The gut microbiota plays a role in drug metabolism, resulting in altered bioavailability of these compounds. Additionally, complex host-microbiome interactions lead to modified xenobiotic metabolism and altered expression of genes involved in drug metabolism. These effects can be at gut tissue-level, or distant, including in the liver. Besides the gut microbiome influencing drug metabolism, drugs also impact the microbial communities in the gut. As different drugs exert selective pressures on the gut microbiome, understanding this bidirectional relationshipis crucial for developing effective therapies for managing chronic inflammation.
... There are theoretical effects of probiotics on acne, including the bacteriocin-like inhibitory substance produced by Streptococcus salivarius resulting in C. acnes inhibition in vitro [80] and evidence that oral Bifidobacterium lactis can improve glucose metabolism and fasting plasma insulin levels in non-insulin-dependent diabetes mellitus mouse models [81]. Bifidobacteria can be reduced by high-fat consumption [82]. Coadministration of a probiotic mix, including Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus, with fatty acids, increases blood levels of anti-inflammatory fatty acids [83]. ...
Article
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Our understanding of the pathogenesis of acne vulgaris is still evolving. It is known that multiple factors impact acne pathophysiology, including genetic, hormonal, inflammatory, and environmental influences. Because of its implications in many of these factors, diet has been a part of the acne discussion for decades. Several studies have evaluated the significance of the glycemic index of various foods and glycemic load in patients with acne, demonstrating individuals with acne who consume diets with a low glycemic load have reduced acne lesions compared with individuals on high glycemic load diets. Dairy has also been a focus of study regarding dietary influences on acne; whey proteins responsible for the insulinotropic effects of milk may contribute more to acne development than the actual fat or dairy content. Other studies have examined the effects of omega-3 fatty acid and γ-linoleic acid consumption in individuals with acne, showing individuals with acne benefit from diets consisting of fish and healthy oils, thereby increasing omega-3 and omega-6 fatty acid intake. Recent research into the effects of probiotic administration in individuals with acne present promising results; further study of the effects of probiotics on acne is needed to support the findings of these early studies. In this review, we discuss the current evidence regarding the diets of US patients with acne and how they may impact acne and acne treatment.
... It is a component of the Gram-negative bacterial membrane that binds to TLR-4-CD14 complex (a pathogen sensor), resulting in the activation of immune system and releases numerous proinflammatory cytokines, which ultimately leads to the development of insulin resistance. [41][42][43] It has been well explained that LPS administration leads to the development of systemic insulin resistance due to induction of acute inflammation. 44 Similarly, upon the administration of LPS, a high-fat diet causes the alteration in gut microbial composition and produces metabolic endotoxemia by increasing intestinal permeability. ...
Article
Human gut microbiota consist of numerous microorganisms, but the most abundant species are Bacteroides and Firmicutes. Each human possesses a specific gut microbiota, which can be altered by diet, antibiotics, lifestyle, and genetic background. Gut microbiota perform vital functions, but in this article, we aimed to elaborate the effects of modified composition of microbiota on host metabolism. Ligands for G protein coupled receptors (GPCRs) are short-chain fatty acids (SCFAs) located on endocrine glands, epithelial cells, and adipocytes. SCFAs are produced in the distal gut by bacterial fermentation of nondigestible polysaccharides; they induce the various beneficial effects including decrease serum glucose level, insulin resistance, as well as inflammation; and they increase glucagon-like peptide-1 (GLP-1) secretion. Fasting-induced adipose factor (FIAF) is suppressed by gut microbiota and results in the increased storage of fatty acids in the adipose tissues and liver. An increased lipopolysaccharide level due to altered gut microflora cause the initiation of inflammation associated with type 2 diabetes mellitus (T2DM). Intestinal dysbiosis and metabolic endotoxemia are considered key mechanisms that seem to be associated with the development of T2DM and obesity. Therapeutic interventions that can be used for the treatment of diabetes include metformin, dietary modulation, probiotics, prebiotics, fecal microbiota transplantation and bariatric surgery.
... Studies have shown that different oral structures and tissues are colonized by distinct microbial communities. Oral microbiome has recently been recognized as a primary mediator for human health [45,46]. ...
Article
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The human microbiome, consisting of the total microbial complement associated with human hosts, is an important emerging area for metagenomic biomarker discovery. Current evidences support that alterations in composition and/or metabolic activity of microbiome play pivotal role in the pathogenesis of many diseases and disorders. Changes in gut microbiota can modulate the peripheral and central nervous systems, resulting in altered brain functioning, and suggesting the existence of a microbiota gut-brain axis. Countless efforts are now underway to develop microbiome-based diagnostics, therapeutics, and services in both the academic and commercial arenas. This paper is a review on the association of microbiome and human health with development of biomarkers.
... They also regulate the gut microbiota and play an important role in immunomodulation 50 . Relation between gut microbiota dysbiosis and metabolic disorders and chronic low-grade inflammation has been established in different studies 51,52 . Beneficial effect of probiotics in alleviating gastrointestinal diseases has been reported by different randomized clinical trials 53,50 . ...
... Butyrate may reach the abdominal adipocytes via bloodstream and eliminate accumulated ROS in differentiated adipocytes. Metabolites such as glutathione (GSH) and SCFAs produced by gut bacteria have been largely recognized to modulate oxidizing conditions toward adipogenesis in adipose tissues 42,56,57 . Our results revealed that electrogenic L. mesenteroides EH-1 is a probiotic candidate for suppression of ROS-associated accumulation of abdominal fat mass. ...
Article
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Although several electrogenic bacteria have been identified, the physiological effect of electricity generated by bacteria on host health remains elusive. We found that probiotic Leuconostoc mesenteroides (L. mesenteroides) can metabolize linoleic acid to yield electricity via an intracellular cyclophilin A-dependent pathway. Inhibition of cyclophilin A significantly abolished bacterial electricity and lowered the adhesion of L. mesenteroides to the human gut epithelial cell line. Butyrate from L. mesenteroides in the presence of linoleic acid were detectable and mediated free fatty acid receptor 2 (Ffar2) to reduce the lipid contents in differentiating 3T3-L1 adipocytes. Oral administration of L. mesenteroides plus linoleic acid remarkably reduced high-fat-diet (HFD)-induced formation of 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species (ROS) biomarker, and decreased abdominal fat mass in mice. The reduction of 4-HNE and abdominal fat mass was reversed when cyclophilin A inhibitor-pretreated bacteria were administered to mice. Our studies present a novel mechanism of reducing abdominal fat mass by electrogenic L. mesenteroides which may yield electrons to enhance colonization and sustain high amounts of butyrate to limit ROS during adipocyte differentiation.
... Thaiss et al. [87] demonstrated using a mouse model of type 1 diabetes mellitus that high blood sugar (hyperglycemia) causes a leaky gut barrier and changes the gut microbiota. This observation contradicts the work by Cani and Delzenne [88] who proposed that the diet caused dysbiosis and barrier dysfunction and as a consequence bacterial endotoxins pass through a leaky gut barrier and drive low grade inflammation. Such an inflammation could be the cause of glucose intolerance and elevated blood sugar in patients. ...
Article
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Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.
... Accumulating studies have revealed that gut microbiota is closely related to host physiology, the pathogenesis of obesity, and metabolic disorder (Ley et al. 2005). Gut microbiota is thus selected as a potential therapeutic target to prevent or treat obesity and its associated diseases (Cani and Delzenne 2009). Increasing studies have shown that the increased ratio of Firmicutes/Bacteroidetes and the decreased abundances of Akkermansia, Bifidobacteria, and other obesity-related bacteria are associated with the progression of obesity in humans and rodents (Liu et al. 2017;Ley et al. 2005;Everard et al. 2013). ...
Article
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Previous studies showed that probiotics supplementation contributed to alleviate obesity. This work was to assess the efficacy of Lactobacillus plantarum FRT10 from sour dough in alleviating obesity in mice fed with a high-fat diet (HFD), and the underlying mechanisms focusing on modulation of the gut microbiota profile. Kunming mice were fed with a regular diet (CT), a high-fat diet (HFD), and two HFDs containing low and high doses of L. plantarum FRT10 for 8 weeks. The physiological and biochemical modulations in liver were analyzed. Cecal contents were analyzed by high-throughput 16S ribosomal RNA sequencing. FRT10 supplementation significantly reduced body weight gain, fat weight, and liver triacylglycerols (TGs) and alanine aminotransferase (ALT) concentrations (P < 0.05). FRT10 significantly ameliorated the HFD-induced gut dysbiosis, as evidenced by increased abundance of microbes, including Butyricicoccus, Butyricimonas, Intestinimonas, Odoribacter, and Alistipes, and decreased abundance of Desulfovibrionaceae, Roseburia, and Lachnoclostridium. Lactobacillus, Bifidobacterium, and Akkermansia were markedly increased after FRT10 intervention. In addition, real-time quantitative PCR revealed that FRT10 upregulated the mRNA expression levels of peroxisome proliferator–activated receptor-α (PPARα) and carnitine palmitoyltransferase-1α (CPT1α), and downregulated the mRNA expression levels of sterol regulatory element–binding protein 1 (SREBP-1) and TG-synthesizing enzyme diacylglycerol acyltransferase 1 (DGAT1) in liver. These findings suggested that FRT10 had anti-obesity effects in obese mice partly related to the activation of PPARα/CPT1α pathway. FRT10 can be considered a single probiotic agent for preventing HFD-induced obesity in humans and animals.
... Probiotics could be defined as 'living microorganisms,' which, when administered in appropriate amounts, provide the host of health benefits. Especially, evidence has been reported that intestinal microbiota regulates systemic energy balance through mechanisms related to the degradation and absorption of gut contents [36,51]. Obesity is associated with a specific profile of intestinal microflora, such as a decrease in the ratio of Bacteroidetes/Firmicutes, the main representative of the gut microbiota [52]. ...
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Our previous study reported that lactic acid bacteria (L. brevis OPK-3) isolated from kimchi ameliorated intracellular lipid accumulation in 3T3-L1 adipocyte. The current study explored potential roles of L. brevis OPK-3 (KLAB) on preventing body weight gain and its effect on the inflammatory response of adipose tissue. Male C57BL/6 mice (n = 10) were divided into four groups: normal diet with distilled water (NDC), high-fat diet with distilled water (HDC), high-fat diet with L-ornithine (OTC) or high-fat diet with KLAB. The KLAB supplement resulted in significantly lower body weight, lower epididymal fat tissue mass, and lower serum and hepatic TG levels than the HDC. KLAB supplementation improved serum cytokines, and real-time polymerase chain reaction (PCR) analysis showed significantly lower inflammatory cytokine mRNA levels in epididymal adipose tissue. These results suggest that the administration of KLAB inhibits the induction of inflammation in adipose tissue along with the inhibition of weight gain. Therefore, this study demonstrates the therapeutic and beneficial value of this strain produced during the fermentation of kimchi.
... The gut microbiota plays major functions in host metabolism and immunity, digestive absorption and nutrient uptake, synthesis of vitamins and prevention of colonization of pathogens through the production of bacterial metabolites which can act in distant organs such as the brain, liver, and also the adipose tissue and which will be involved in host-microbiota interactions [199]. Obesity and insulin resistance in humans and rodents are associated with intestinal dysbiosis which is characterized by the enrichment of certain species of bacteria to the detriment of others (e.g., a change in the ratio of Firmicutes and Bacteroidetes which are the two dominant phyla representing more than 90% of the total community) with changes in the composition of the gut microbiota [200,201]. The gut-adipose axis depends on communication through short-chain fatty acids (SCFAs) and bile acids (BAs) which behave as hormone-like products signaling through G protein-coupled receptors (GPRs) expressed in the adipose tissue [202,203]. ...
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Obesity and metabolic-related diseases, among which diabetes, are prominent public health challenges of the 21st century. It is now well acknowledged that pollutants are a part of the equation, especially endocrine-disrupting chemicals (EDCs) that interfere with the hormonal aspect. The aim of the review is to focus on adipose tissue, a central regulator of energy balance and metabolic homeostasis, and to highlight the significant differences in the endocrine and metabolic aspects of adipose tissue between males and females which likely underlie the differences of the response to exposure to EDCs between the sexes. Moreover, the study also presents an overview of several mechanisms of action by which pollutants could cause adipose tissue dysfunction. Indeed, a better understanding of the mechanism by which environmental chemicals target adipose tissue and cause metabolic disturbances, and how these mechanisms interact and sex specificities are essential for developing mitigating and sex-specific strategies against metabolic diseases of chemical origin. In particular, considering that a scenario without pollutant exposure is not a realistic option in our current societies, attenuating the deleterious effects of exposure to pollutants by acting on the gut-adipose tissue axis may constitute a new direction of research.
... A mixture of prebiotics specifically increased the abundance of Bifidobacterium spp., which improved systemic and hepatic inflammation, intestinal integrity and endotoxemia. The findings suggest that modifications on host microbiota affect the host immune status and gut integrity (41). In-vitro stimulation of intestinal epithelial cells with TLR-2 ligands induced the redistribution of tight junction proteins, resulting in an improved monolayer integrity. ...
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Systemic Lupus Erythematosus is a complex autoimmune disease and its etiology remains unknown. Increased gut permeability has been reported in lupus patients, yet whether it promotes or results from lupus progression is unclear. Recent studies indicate that an impaired intestinal barrier allows the translocation of bacteria and bacterial components into systemic organs, increasing immune cell activation and autoantibody generation. Indeed, induced gut leakage in a mouse model of lupus enhanced disease characteristics, including the production of anti-dsDNA antibody, serum IL-6 as well as cell apoptosis. Gut microbiota dysbiosis has been suggested to be one of the factors that decreases gut barrier integrity by outgrowing harmful bacteria and their products, or by perturbation of gut immune homeostasis, which in turn affects gut barrier integrity. The restoration of microbial balance eliminates gut leakage in mice, further confirming the role of microbiota in maintaining gut barrier integrity. In this review, we discuss recent advances on the association between microbiota dysbiosis and leaky gut, as well as their influences on the progression of lupus. The modifications on host microbiota and gut integrity may offer insights into the development of new lupus treatment.
... Recent animal and clinical experiments have confirmed that the altered gut microbiota as a critical environmental factor was also involved in host metabolic disorders (Li & Ji, 2018;Malik et al., 2013;Wolf & Lorenz, 2012), including cardiovascular disease, hypertension, diabetes mellitus, dyslipidemia, and fatty liver disease (Aron-Wisnewsky et al., 2013;Song & Chan, 2019). For example, the gut microbiota disorder caused by high-fat feeding was characterized by a higher proportion of Firmicutes and a lower proportion of Bacteroidetes (Cani & Delzenne, 2009). Abnormal changes in the composition of the intestinal flora might also affect the intestinal barrier, thereby changing the intestinal-liver axis, and promoting the production of obesityrelated inflammatory cytokines in non-alcoholic fatty liver disease (Porras et al., 2017). ...
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The current study employed high‐fat diet (HFD) induced murine model to assess the relationship between the lipid‐lowering effect of aged citrus peel (chenpi) extract and the alterations of gut microbiota. The results showed that intake of chenpi extract for 12 week dose‐dependently suppressed HFD‐induced body weight, food intake, Lee's index, together with decreased the level of fasting blood glucose, total cholesterol, triglyceride, and low‐density lipoprotein cholesterol. Moreover, chenpi extract administration up‐regulated the abundance and diversity of fecal microbiota and down‐regulated the ratio of Firmicutes‐to‐Bacteroidetes, which was characterized by the lower family of Lachnospiraceae, Helicobacteraceae, and Desulfovibrionaceae, and higher family of Bacteroidales_S24‐7, Bacteroidaceae, Rikenellaceae, and Ruminococcaceae. Consistently, at the genus levels, chenpi extract treatment reversed the expansions of Helicobacter, Lachnospiraceae_UCG‐006, and Desulfovibrio, while increased the abundance of Bacteroides, Rikenellaceae_RC9_gut_group, and Alistipes (belonging to Rikenellaceae family), Anaerotruncus and Odoribacter (belonging to Ruminococcaceae family), which were significantly negatively correlated with the levels of the serum lipid parameters. In conclusion, our findings indicated that anti‐obesity ability of chenpi extract might be related to the improvement of gut microbiota imbalance. Practical applications With the improvement of living standards, the incidence of metabolic diseases such as obesity, hypertension, and diabetes has increased significantly, and it has become a public health problem that seriously affects the health of the people. Chenpi contains a large amount of active ingredients, flavonoids, and other compounds, which can promote the absorption of the digestive system and have good effects on diseases such as the cardiovascular system. Our previous study has confirmed that the chenpi extract effectively regulated the glucose and lipid metabolism disorder induced by high‐fat diet. However, it is not clear whether the effect is closely related to the improvement of gut microbiota. Accordingly, our result would provide a theoretical basis for future research on the relationship between obesity, chenpi extract, and gut microbiota, and support additional understanding of its potential anti‐obesity effects.
... In their animal study, Vida et al. showed that the chronic replacement of IL-6 with physiological doses in IL-6-/-mice seriously exacerbated the steatosis induced by a highfat diet (31). In the present study, the increasing of these two cytokines was associated with steatosis and fibrosis, but this may be due to their ability to work on mitochondria function and oxidation (32,33). Notably, these cytokines were correlated with transaminase levels and with the severity of the steatohepatitis, suggesting that they may be important mediators in NAFLD-to-NASH progression. ...
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Aim: The associations between serum levels of melatonin and concentrations of tumor necrosis factor (TNF)-a and interleukin (IL)-6 were assessed among patients with different degrees of non-alcoholic fatty liver disease. Background: Non-alcoholic fatty liver disease (NAFLD) has become a very common worldwide disease. Methods: In this cross-sectional study, adult patients diagnosed with fatty liver disease by Fibroscan evaluation were included if they met the inclusion/exclusion criteria for NAFLD. The participants were categorized into the three following groups: 1) fibrosis> 9.1KP and steatosis >290 dbm; 2) fibrosis: 6-9.0 KP and steatosis 240-285; and 3) fibrosis < 5.8 KP and steatosis<240 dbm. Post-fasting, 5 ml of venous blood was collected for laboratory assessment, and a questionnaire including demographic, anthropometric, laboratories and clinical data was completed. Results: A total of 97 participants were included. The mean age was 42.21±11 years, and 59 patients (60.0%) were female. Melatonin levels as well as pro-inflammatory cytokines levels were correlated with advancing fibrosis and steatosis in univariate analysis. A significant association was observed between these cytokines and advancing fibrosis, severe steatosis levels, and melatonin concentrations. Furthermore, in the multiple linear regression model, melatonin levels showed a significant association with these cytokines. Conclusion: Melatonin may have protective effects on tissue injury during advancing liver fibrosis via cytokines modulation. Therefore, it can be considered as a potential therapeutic management strategy for NAFLD.
... These changes may, in turn, add to disease susceptibility [65]. Intestinal dysbiosis has been linked to chronic low-grade inflammation [66]; metabolic disorders [67] leading to metabolic syndromes, for example, obesity and diabetes [60,68,69]; infections in the gastrointestinal tract (GIT); irritable bowel syndrome (IBS); and inflammatory bowel disease (IBD) [60,70]. Obesity also relates to dysbiosis and occurs due to the alteration in the microbiota at the phylum level and changes in the representation of bacterial genes and metabolic pathways, where a set of core microbial biomarkers affect the metabolisms [62]. ...
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The human gut microbiota is vital for maintaining human health in terms of immune system homeostasis. Perturbations in the composition and function of microbiota have been associated with several autoimmune disorders, including myasthenia gravis (MG), a neuromuscular condition associated with varying weakness and rapid fatigue of the skeletal muscles triggered by the host’s antibodies against the acetylcholine receptor (AChR) in the postsynaptic muscle membrane at the neuromuscular junction (NMJ). It is hypothesized that perturbation of the gut microbiota is associated with the pathogenesis of MG. The gut microbiota community profiles are usually generated using 16S rRNA gene sequencing. Compared to healthy individuals, MG participants had an altered gut microbiota’s relative abundance of bacterial taxa, particularly with a drop in Clostridium. The microbial diversity related to MG severity and the overall fecal short-chain fatty acids (SCFAs) were lower in MG subjects. Changes were also found in terms of serum biomarkers and fecal metabolites. A link was found between the bacterial Operational Taxonomic Unit (OTU), some metabolite biomarkers, and MG’s clinical symptoms. There were also variations in microbial and metabolic markers, which, in combination, could be used as an MG diagnostic tool, and interventions via fecal microbiota transplant (FMT) could affect MG development. Probiotics may influence MG by restoring the gut microbiome imbalance, aiding the prevention of MG, and lowering the risk of gut inflammation by normalizing serum biomarkers. Hence, this review will discuss how alterations of gut microbiome composition and function relate to MG and the benefits of gut modulation.
... There are millions of bacteria present in the gut, the majority of which are commensals. Although the actual composition of the gut microbiota is unclear, current research has revealed that 80-90% of bacteria morphologies belong to two phyla: Bacteroides and Firmicutes [2]. In addition to nutritional consumption, antibiotics, stress, and obesity; pregnancy has been proven to cause alteration in the gut microbiota composition. ...
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Background: The primary purpose of the study is to determine the variation of gut microbiota composition between first (T1) and third trimester (T3); gestational diabetes mellitus (GDM) and non-gestational diabetes mellitus (NGDM); and also within a different category of Body Mass Index (BMI) of selected pregnant Malaysian women. Methods: A prospective observational study on selected 38 pregnant Malaysian women attending a tertiary medical centre was carried out. Those with preexisting diabetes, metabolic syndrome or any other endocrine disorders were excluded. GDM was determined using oral glucose tolerance test (OGTT) while BMI was stratified as underweight, normal, pre-obese and obese. Fecal samples were then collected during the first trimester (T1) and the third trimester (T3). The V3-V4 region of 16S rRNA gene amplicon libraries were sequenced and analyzed using QIIME (version 1.9.1) and METAGENassist. Results: Twelve women (31.6%) were diagnosed as GDM. A trend of lower α-diversity indices in GDM, pre-obese and obese pregnant women were observed. Partial Least Squares Discriminant Analysis (PLS-DA) shows a clustering of gut microbiota according to GDM status and BMI, but not by trimester. Genera Acidaminococcus, Clostridium, Megasphaera and Allisonella were higher, and Barnesiella and Blautia were lower in GDM group (P < 0.005). Obese patients had gut microbiota that was enriched with bacteria of Negativicutes and Proteobacteria class such as Megamonas, Succinatimonas and Dialister (P < 0.005). The normal and mild underweight profiles on the other hand had a higher bacteria from the class of Clostridia (Papillibacter, Oscillibacter, Oscillospira, Blautia, Dorea) and Bacteroidia (Alistipes, Prevotella, Paraprevotella) (P < 0.005). Conclusion: The prevalence and variation of several key bacteria from classes of Negativicutes, Clostridia and Proteobacteria has potential metabolic links with GDM and body weight during pregnancy which require further functional validation.
... Translocation of bacteria or bacteria-derived metabolites from the gut and subsequent mesenteric visceral adipose tissue inflammation in obesity has been postulated to occur in when the gut barrier function is impaired 5 . Indeed, in animal models, obesity is associated with increased intestinal permeability and translocation of gut-derived lipopolysaccharide (LPS) 27,28 . In turn, this has been shown to drive chronic low-grade inflammation and subsequent insulin resistance, a mechanism that has been dubbed metabolic endotoxemia 28 ...
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Aims Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. Material and Methods Eight individuals with clinically severe obesity (BMI >35 kg/m²) and metabolic syndrome received lean donor fecal microbiota transplantation 4 weeks prior to elective bariatric surgery. The participants were age-, sex- and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. Results Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. Conclusions Visceral bacterial DNA content and level of inflammation were not altered upon fecal microbiota transplantation. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity. This article is protected by copyright. All rights reserved.
... 21 These endothelial changes can also be due to oxidative stress. 8 The gut microbiota plays an important role in lowering blood pressure, 22 reducing inflammation, 23 hemostasis, glucose metabolism, 24 and body mass index. 25 These supplements play a positive role in reducing oxidative stress and systemic inflammation. ...
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Introduction:Antioxidants and anti-inflammatory drugs have been suggested to treat preeclampsia. This systematic review and meta-analysis was conducted to investigate the efficacy of probiotic or synbiotic supplementation on hypertensive disorders in women with gestational diabetes mellitus (GDM).Methods:The databases including Cochrane, Embase, Ovid, ProQuest, Scopus, Web of Science, and PubMed were systematically searched for collecting the randomized controlled trials (RCTs) investigating the efficacy of probiotic or synbiotic supplementation versus placebo on hypertensive disorders and pregnancy outcomes in GDM until July 2020.Results:Five RCTs with a total sample size of 402 women were included in the meta-analysis. There was no significant decline in systolic blood pressure (standardized mean difference [SMD] = -3.41, 95% confidence interval [CI] = -8.32 to 1.50, P = 0.17), diastolic blood pressure (SMD = -5.11, 95% CI = -14.20 to -3.98, P = 0.27), preeclampsia (odds ratio [OR] = 1.56, 95% CI = 0.61 to 3.98, P = 0.35), cesarean section (OR = 0.52, 95% CI = 0.18 to 1.50, P = 0.23), and macrosomia (OR = 0.81, 95% CI = 0.41 to 1.57, P = 0.53). No significant increase was observed in terms of 5-minute Apgar (SMD = 0.16, 95% CI = -0.06 to 0.39, P = 0.15, I2= 0%), birth weight (SMD = -0.18, 95% CI = -0.43 to 0.06, P = 0.13, I2= 0%), and gestational age (SMD = 0.13, 95% CI = -0.11 to 0.37, P = 0.28, I2= 0%).Conclusion:Probiotic or synbiotic supplements are not associated with significant effects on pregnancy outcomes in GDM. However, due to the limited number of studies in this regard and heterogeneity between studies, future high-quality RCTs are recommended.
... A high-fat diet induces obesity and causes intestinal microecological disorders characterized by an increase in the number of Gram-negative bacteria, resulting in increased lipopolysaccharide content, intestinal mucosal permeability, and metabolic endotoxemia (Cani and Delzenne 2009). However, most reports studied changes in intestinal microbiota after obesity or a disease model was established. ...
Article
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Obesity is often associated with intestinal microbiota imbalance and increased Gram-negative bacteria characterized by higher endotoxin levels. Therefore, a study on the joint effects of a high-fat diet and Gram-negative bacteria prechallenge might provide further information on the interactive effects of intestinal microbiota and obesity as well as the effects of a probiotic intervention on these processes. This study focused on the joint effects of a high-fat diet and Escherichia coli on mouse inflammatory cytokines, intestinal microbiota, hepatic pathological changes, and the alleviating capacity of probiotics (Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus fermentum). Our results showed that E. coli administration and the high-fat diet exacerbated the inflammatory syndrome by increasing the visceral fat content, the inflammatory cell infiltration, and intestinal microbiota disorder in mice. E. coli administration caused a decrease in short-chain fatty acids in mouse feces, and probiotics effectively improved this phenomenon. Compound probiotic intervention reduced LPS and IL-1β levels, while increased IL-10 levels in mice improved the degeneration and inflammatory infiltration of mouse liver cells. The intestinal microbiota showed great differences at 3 weeks and 6 weeks post-administration. High fat and E. coli alone or in combination caused intestinal microbiota disorder, with increased harmful bacteria, and the probiotics effectively improved the intestinal flora structure and increased the fecal short-chain fatty acid (SCFA) content. In conclusion, a high-fat diet and Gram-negative bacteria challenge exacerbated the inflammatory syndrome, which can be alleviated by compound probiotic intervention.
... Restoration of gut homeostasis is considered a potential target for therapeutic strategies, since dysbiosis of gut microbiota is thought to be influenced by various diseases 6,7 . Many studies have discussed the relationships between gut microbiota and diseases such as AD, obesity, diabetes, immunological diseases, and neurological diseases [8][9][10] . Previous studies on AD have reported the effects of probiotic treatment on patients with AD through gut microbiota diversity manipulation or reduction, which were not always beneficial 3,[11][12][13] . ...
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The pathogenesis of atopic dermatitis (AD) involves complex factors, including gut microbiota and immune modulation, which remain poorly understood. The aim of this study was to restore gut microbiota via fecal microbiota transplantation (FMT) to ameliorate AD in mice. FMT was performed using stool from donor mice. The gut microbiota was characterized via 16S rRNA sequencing and analyzed using Quantitative Insights into Microbial Ecology 2 with the DADA2 plugin. Gut metabolite levels were determined by measuring fecal short-chain fatty acid (SCFA) contents. AD-induced allergic responses were evaluated by analyzing blood parameters (IgE levels and eosinophil percentage, eosinophil count, basophil percentage, and monocyte percentage), the levels of Th1 and Th2 cytokines, dermatitis score, and the number of mast cells in the ileum and skin tissues. Calprotectin level was measured to assess gut inflammation after FMT. FMT resulted in the restoration of gut microbiota to the donor state and increases in the levels of SCFAs as gut metabolites. In addition, FMT restored the Th1/Th2 balance, modulated Tregs through gut microbiota, and reduced IgE levels and the numbers of mast cells, eosinophils, and basophils. FMT is associated with restoration of gut microbiota and immunologic balance (Th1/Th2) along with suppression of AD-induced allergic responses and is thus a potential new therapy for AD.
... In addition, the SCFAs contribute to strengthening the immune system, glucose regulation and prevents obesity [7]. On the contrary, gut microbial dysbiosis is the leading cause of numerous chronic [8] and metabolic diseases [9]. ...
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Lactose is the most abundant by-product of the dairy industry and is increasingly recognized as an important feedstock to produce value-added compounds. Lactulose and epilactose are valuable prebiotics that can be generated from lactose with cellobiose 2-epimerases (CEases). Here we describe the characterization of the two CEases CbCEP and RfCEP, originated from the thermophilic microorganism Caldicellulosiruptor bescii and the mesophilic microorganism Roseburia faecis, respectively. CbCEP showed exceptional pH and temperature stability, with maximal activity at pH 7.5 and 70 °C. RfCEP exhibited maximum activity at 50 °C and pH 8. Under optimal conditions in small-scale experiments with commercial lactose, CbCEP produced both lactulose and epilactose with yields of 29.8% and 21.6%, respectively, while RfCEP produced only epilactose with a yield of 19.3%. Furthermore, we evaluated the application of CbCEP for lactulose and epilactose production in stirred fermenters at two different temperatures (70 and 30 °C) at a scale of 5 L volume and a concentration of cheese-whey permeate of 50 g/L. At 70 °C, lactulose was the predominant product of CbCEP-mediated lactose conversion, with a final yield of 30% (12.8 g/L) lactulose and 24.7% (10.6 g/L) epilactose. At 30 °C, lactose was mainly converted into epilactose, with a final yield of 35 % (14.9 g/L), and a minor amount of lactulose (final yield of 4.3% (1.8 g/L). The findings presented here may guide the design of an industrial strategy, based on the temperature-tunable activity of CbCEP, for production of valuable lactose derivatives at high yields directly from whey permeate.
Article
Overweight and obesity are growing health problems in domestic cats, increasing the risks of insulin resistance, lipid dyscrasias, neoplasia, cardiovascular disease, and decreasing longevity. The signature of obesity in the feline gut microbiota has not been studied at the whole-genome metagenomic level. We performed whole-genome shotgun metagenomic sequencing in the fecal samples of eight overweight/obese and eight normal cats housed in the same research environment. We obtained 271 Gbp of sequences and generated a 961-Mbp de novo reference contig assembly, with 1.14 million annotated microbial genes. In the obese cat microbiome, we discovered a significant reduction in microbial diversity (P < 0.01) and Firmicutes abundance (P = 0.005), as well as decreased Firmicutes/Bacteroidetes ratios (P = 0.02), which is the inverse of obese human/mouse microbiota. Linear discriminant analysis and quantitative PCR (qPCR) validation revealed significant increases of Bifidobacterium sp., Olsenella provencensis, Dialister sp.CAG:486, and Campylobacter upsaliensis as the hallmark of obese microbiota among 400 enriched species, whereas 1,525 bacterial species have decreased abundance in the obese microbiome. Phascolarctobacterium succinatutens and an uncharacterized Erysipelotrichaceae bacterium are highly abundant (>0.05%) in the normal gut with over 400-fold depletion in the obese microbiome. Fatty acid synthesis-related pathways are significantly overrepresented in the obese compared with the normal cat microbiome. In conclusion, we discovered dramatically decreased microbial diversity in obese cat gut microbiota, suggesting potential dysbiosis. A panel of seven significantly altered, highly abundant species can serve as a microbiome indicator of obesity. Our findings in the obese cat microbiome composition, abundance, and functional capacities provide new insights into feline obesity. IMPORTANCE Obesity affects around 45% of domestic cats, and licensed drugs for treating feline obesity are lacking. Physical exercise and calorie restrictions are commonly used for weight loss but with limited efficacy. Through comprehensive analyses of normal and obese cat gut bacteria flora, we identified dramatic shifts in the obese gut microbiome, including four bacterial species significantly enriched and two species depleted in the obese cats. The key bacterial community and functional capacity alterations discovered from this study will inform new weight management strategies for obese cats, such as evaluations of specific diet formulas that alter the microbiome composition, and the development of prebiotics and probiotics that promote the increase of beneficial species and the depletion of obesity-associated species. Interestingly, these bacteria identified in our study were also reported to affect the weight loss success in human patients, suggesting translational potential in human obesity.
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The pharmacokinetic properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the pharmacokinetics of simvastatin. An open‐label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for pharmacokinetic analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of microbiota considerably decreased, and the composition was altered. In particular, the relative abundance of Bacteroidetes decreased, while that of Proteobacteria increased. In addition, changes in fecal metabolites, including D‐glucuronic acid, were observed. However, systemic exposure of simvastatin was not changed while that of hydroxysimvastatin showed a tendency to increase. The relationship between the change of pharmacokinetics of simvastatin and the change of gut microbiota and fecal metabolites were not clearly observed.
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Poor diet quality influences cardiometabolic risk. Although potatoes are suggested to adversely affect cardiometabolic health, controlled trials that can establish causality are limited. Consistent with potatoes being rich in micronutrients and resistant starch, we hypothesized that their inclusion in a Dietary Guidelines for Americans (DGA)-based dietary pattern would improve cardiometabolic and gut health in metabolic syndrome (MetS) persons. In a randomized cross-over trial, MetS persons (n = 27; 32.5 ± 1.3 year) consumed a DGA-based diet for 2 weeks containing potatoes (DGA + POTATO; 17.5 g/day resistant starch) or bagels (DGA + BAGEL; 0 g/day resistant starch) prior to completing oral glucose and gut permeability tests. Blood pressure, fasting glucose and insulin, and insulin resistance decreased (p < 0.05) from baseline regardless of treatment without any change in body mass. Oral glucose-induced changes in brachial artery flow-mediated dilation, nitric oxide homeostasis, and lipid peroxidation did not differ between treatment arms. Serum endotoxin AUC0–120 min and urinary lactulose/mannitol, but not urinary sucralose/erythritol, were lower in DGA + POTATO. Fecal microbiome showed limited between-treatment differences, but the proportion of acetate was higher in DGA + POTATO. Thus, short-term consumption of a DGA-based diet decreases cardiometabolic risk, and the incorporation of resistant starch-containing potatoes into a healthy diet reduces small intestinal permeability and postprandial endotoxemia.
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Scope Synthetic emulsifiers have recently been shown to promote metabolic syndrome and considerably alter gut microbiota. Yet, data is lacking regarding the effects of natural emulsifiers, such as plant lecithins rich in essential α‐linolenic acid (ALA), on gut and metabolic health. Methods and Results For 5 days, male Swiss mice were fed diets containing similar amounts of ALA and 0, 1, 3 or 10% rapeseed lecithin (RL) or 10% soy lecithin (SL). Following an overnight fast, they were force‐fed the same oil mixture and euthanised after 90min. The consumption of lecithin significantly increased faecal levels of Clostridium leptum (p = 0.0004), regardless of origin or dose, without altering hepatic or intestinal expression of genes of lipid metabolism. 10%‐RL increased ALA abundance in plasma triacylglycerols at 90min, reduced caecal bile acid hydrophobicity and increased their sulfatation, as demonstrated by the increased hepatic RNA expression of Sult2a1 (p = 0.037) and caecal CA‐7S concentration (p = 0.05) versus 0%‐lecithin. Conclusion After only 5 days, nutritional doses of RL and SL modified gut bacteria in mice, by specifically increasing Clostridium leptum group. RL also increased postprandial ALA abundance and induced beneficial modifications of the bile acid profile. ALA‐rich lecithins, especially RL, may then appear as promising natural emulsifiers. This article is protected by copyright. All rights reserved
Chapter
Homeostasis is the dynamic process of maintaining self-balance or to put alternatively the body’s natural tendency to poise equilibrium in response to external stimuli and reorient itself toward undulating environmental circumstances. Various physiochemical and biological processes work in tandem to maintain homeostasis. The microbiota allied to host is an important biological intermediary that plays a pivotal role in maintaining this homeostasis. It consists of a myriad of commensal and symbiotic microbes which are an important dynamic determinant of human health. The host-health promoting microbes, known as probiotics, are the center of intense research which has been extensively reviewed in the previous chapters. It has become patently evident in the recent years that the gut microbiome and the brain communicate in a bidirectional fashion with a great possibility of mutual implication pertaining to each other’s functions. Modulation of intestinal microbiota with probiotics is used as a therapeutic modality in prevention and treatment of a multitude of ailments. Emerging evidence from interdisciplinary research corroborates the incident of communication axis between various organs, for instance, the brain–gut or brain–skin axis. In this chapter with reliance placed on prior published compelling evidence from extant literature, we aim to endeavor and comprehensively comprehend the underlying mechanism which further helps to unravel the interrelationship between gut–brain–skin axis and the modulation of their microbiota by deployment of designer probiotics. The chapter also presents fresh impetus on the evidence demonstrating how the gut microbiome may possibly affect brain function in adults, thereby having an extensive impact on neurological disorders.
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Polydextrose (PDX) is a branched glucose polymer, utilized as a soluble dietary fiber. Recently, PDX was found to have hypolipidemic effects and effects on the gut microbiota. To investigate these findings more closely, a non-targeted metabolomics approach, was exploited to determine metabolic alterations in blood and epididymal adipose tissue samples that were collected from C57BL/6 mice fed with a Western diet, with or without oral administration of PDX. Metabolomic analyses revealed significant differences between PDX- and control mice, which could be due to differences in diet or due to altered microbial metabolism in the gut. Some metabolites were found in both plasma and adipose tissue, such as the bile acid derivative deoxycholic acid and the microbiome-derived tryptophan metabolite indoxyl sulfate, both of which increased by PDX. Additionally, PDX increased the levels of glycine betaine and l-carnitine in plasma samples, which correlated negatively with plasma TG and positively correlated with bacterial genera enriched in PDX mice. The results demonstrated that PDX caused differential metabolite patterns in blood and adipose tissues and that one-carbon metabolism, associated with glycine betaine and l-carnitine, and bile acid and tryptophan metabolism are associated with the hypolipidemic effects observed in mice that were given PDX.
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Article de synthèse bibliographique portant sur les fascinantes recherches en génétique du microbiome humain.
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Microorganisms that provide health benefits to the host when consumed in the right proportions are called Probiotics. Certain lactic acid bacteria (LAB) have been considered probiotics with proven health benefits. These probiotics have been used extensively for human health. In this study, in vivo evaluation was conducted to determine the count of microflora in the fecal of Wistar rats, which were given fermented milk with probiotic Pediococcus acidilactici BK01. Pediococcus acidilactici BK01 is a LAB with probiotic use, isolated from Bekasam (fermented fish). This research was conducted in vivo on 24 male rats (Wistar Rat). This study contain in 4 treatment groups. Each group contains six male rats. The results showed a significant increase in the group of rats given fermented milk compared to the control group (without fermented milk). The probiotics of fermented milk have significantly reduced the count of E.coli and not on the total aerobic bacteria. The conclusion of this study, probiotic of fermented milk Pediococcus acidilactici BK01, can increase the total microflora of lactic acid bacteria and reduce the number of pathogenic bacteria.
Thesis
Des études récentes ont montré que le microbiote participe à l’homéostasie intestinale en contribuant au développement morphologique, à l’éducation du système immunitaire, aux mécanismes de défense de l’hôte et à la régulation du métabolisme. Une dysbiose de ce microbiote ainsi qu’une réduction de la diversité bactérienne a été observé dans diverses pathologies chroniques telles que les maladies inflammatoires chroniques (MICI) et l’obésité. Le microbiote constitue donc une cible thérapeutique de choix dans la prise en charge de ces maladies chroniques. Les probiotiques, microorganismes bénéfiques pour l’hôte représentent une alternative intéressante, mais dont les critères de sélection nécessitent d’être améliorés.Dans une première étude, nous avons pu mettre en évidence les propriétés bénéfiques d’un mélange de deux probiotiques comprenant un bifide et un lactobacille dans un modèle murin d’obésité résultant d’une alimentation riche en graisses (Alard et al, 2016). Ce mélange probiotique a réduit significativement la prise de poids, amélioré les paramètres inflammatoires et métaboliques dont l’insulino-résistance, et augmenté l’expression intestinale des récepteurs aux acides gras à chaine courte (AGCC). Il a également favorisé dans un système d’intestin artificiel la production de butyrate et propionate ; principaux AGCCs. Les effets protecteurs ont été associés à l’amélioration de la dysbiose du microbiote, notamment la restauration de l’abondance d’Akkermansia muciniphila.L’objectif principal de cette thèse a été ensuite de sélectionner au sein d’une collection de 23 souches bactériennes provenant de la société PiLèJe, une ou plusieurs souche(s) probiotique(s) possédant des propriétés protectrices contre les MICI et l’obésité. Les propriétés immuno-modulatrices des souches ainsi que leur capacité à renforcer la barrière intestinale ont été étudiées in vitro à l’aide cellules mononuclées sanguines humaines, puis dans un modèle in vitro de perméabilité membranaire, induite par la sensibilisation d’une monocouche de cellules Caco-2 par de l’eau oxygénée. Six souches ont été sélectionnées, cinq souches induisant de forts niveaux de la cytokine anti-inflammatoire IL-10 et capables de restaurer la barrière intestinale et une souche capable de renforcer fortement cette barrière. Ces souches ont été ensuite évaluées en modèles in vivo de colite chronique et aigüe induite par du TNBS (2,4,6 trinitrobenzene sulfonic acid). De façon intéressante les souches protégeant en colite aigüe ne protègent pas aussi efficacement en colite chronique et inversement.Nous avons poursuivi la sélection de souches ou mélanges de souches dans le contexte de l’obésité et des maladies métaboliques associées. Nous avons utilisé les mêmes critères que précédemment (capacités anti-inflammatoires et à restaurer la barrière intestinale) complétés par l’étude de la capacité des souches à limiter l’accumulation des lipides dans un modèle in vitro de différenciation adipocytaire basé sur l’utilisation de la lignée 3T3-L1 et à induire la sécrétion de peptides entéro-endocrines impliqués notamment dans la satiété par l’utilisation de la lignée murine de cellules entéro-endocrine STC-1. Trois mélanges de souches et une souche seule ont été sélectionnées et évaluées dans un modèle murin d’obésité induite par un régime hyperlipidique à 45% de gras. Nous avons pu mettre en évidence des capacités positives d’un mélange de deux souches et d’une souche seule à réduire la prise de poids, ainsi que l’inflammation dans le tissu adipeux.Ces résultats indiquent que des criblages in vitro basés sur l’étude des propriétés immunomodulatrices, des capacités à restaurer la barrière, à diminuer l’accumulation des lipides et à induire des peptides de satiété, permettent une pré-sélection de souches ou mélanges de souches ayant un effet protecteur et démontrent à nouveau que les capacités bénéfiques des probiotiques sont souche-dépendantes et spécifiques des modèles ciblés.
Chapter
Gut microbiome can be defined as the microorganisms’ inhabitat in the gastrointestinal tract including bacteria, viruses, protozoa, and fungi and their collective genetic material present within it. The gut microbiota has long been of research interest due to their importance to human health, nutrition, and well-being. A healthy gut microbiota (properly balanced bacterial groups) is normally required for human health to maintain host immune homeostasis including skin, nutrient intake, as well as gut development. An unbalanced gut microbiota or dysbiosis in microbes often leads to occurrence of both acute and chronic diseases, such as infectious diarrhea, inflammatory bowel diseases, obesity, diabetes, colon cancer, and neonatal necrotizing enterocolitis; not only metabolism-related disease, but also skin diseases like acne vulgaris and atopic dermatitis, in addition to psychological problems such as depression and autism. The human and other genome projects that have been completed as well as the ongoing human microbiome project give rise to revolutionary technologies characterized by culture-independent, high-throughput, particularly next-generation DNA sequencing and bioinformatics analyses. These robust, powerful methods have enabled more comprehensive studies on the gut microbiota and their functions including interaction with host and diet. New knowledge on the modulation of gut microbiota by dietary fiber is critical for the development of effective strategies to improve human health and to treat microbiota-associated diseases. This chapter focuses on the significance and various factors affecting gut microbiota, along with associated disorders. Additionally, the gut microbiome brain and skin axis and various methodologies to study gut microbiota are also discussed.
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Obesity is fast becoming a worldwide health concern and causes a chronic state of oxidative stress and low-grade inflammation, which could be major risk factors for a number of chronic diseases. We investigated the potential of the 61 probiotic candidates isolated from infant feces towards activity of lipid accumulation inhibition, and then we extended the study to evaluate their antidiabetic and antioxidant activity. Seven strains were finally selected based on their ability to inhibit lipid accumulation (>60%) and productivity yield (>1 × 1011 colony forming units [CFU]/g): Lactobacillus acidophilus MG4558; Lactobacillus paracasei MG4592; Lactobacillus plantarum MG4553 and MG4555; and Lactobacillus rhamnosus MG4502, MG4511, and MG4505. Selected strains showed high α-glucosidase-inhibiting activity (> 50%), except for MG4511 (19.8%), and similar antioxidant activities were reflected by the results of DPPH (21.6–27.5%) and ABTS (40.9–44.9%) assays. With respect to their functional properties as probiotics, most of the strains were resistant to simulated gastric (pH 3 and 4) and intestinal (pH 7 and 8) fluids, and possessed various probiotic-related factors, including autoaggregation ability, antibiotic susceptibility, enzyme production, and biochemical profiles, and were non-hemolytic. We conclude that our strains may be good probiotic candidates for functional food ingredients to prevent metabolic disorders such as obesity and diabetes.
Thesis
Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease among youth in the United States. This recent rise of NAFLD may be partially due to perinatal programming, where in utero exposures alter the lifelong health trajectory of offspring. Maternal pregnancy diet and endocrine disrupting chemical exposure have been identified as drivers of perinatal programming. However, the potential for maternal diet to modify the impact of perinatal chemical exposure is not well understood. This dissertation examined whether perinatal exposure to two common environmental toxicants, bisphenol A (BPA) and high fat diets (HFDs), would affect NAFLD incidence in offspring. A longitudinal mouse exposure study and a human birth cohort were used to investigate this hypothesis and to evaluate the translation of findings across species. Oral exposure to one of six diets: Control, Western HFD, Mediterranean HFD or each diet with 50ug BPA/kg added, occurred pre-gestation through lactation. All mice were weaned onto the Control diet, thus isolating exposure to the perinatal period. Offspring NAFLD was assessed via hepatic steatosis and hepatic oxidative response at postnatal day 10 (PND10) and 10-months. Hepatic triglyceride (TG) levels were altered by perinatal HFD in dams, but in offspring perinatal exposures affected metabolic outcomes not hepatic TGs. Hepatic histology from 10-month offspring highly correlated with hepatic TG levels, validating the TG findings. Hepatic 8-isoprostane (8-iso) levels differed by perinatal exposure in PND10 and 10-month offspring, but alterations were age and sex-specific. Perinatal HFD and BPA minimally impacted offspring redox parameters (EhGSH, EhCys, S-glut), suggestive of greater homeostatic control of these parameters compared to lipid oxidation. Dam metabolic phenotype significantly altered offspring hepatic steatosis and oxidative response, even when perinatal HFD and BPA did not, emphasizing the critical role of the maternal environment on offspring health. The impact of maternal BPA exposure and gestational Mediterranean diet adherence (MDS) on the metabolic health of peripubertal youth was examined in a well-established human birth cohort. Youth metabolic and oxidative health was assessed via metabolic risk score (MRS) and serum 8-iso. Maternal pregnancy average and Trimester 2 BPA were associated with a suggestive decrease in youth MRS driven by boys, but a suggestive increase in 8-iso levels driven by girls. Maternal MDS did not affect youth MRS, but altered youth serum 8-iso in opposite directions based on sex. Additional youth characteristics (peripubertal BPA, MDS, vigorous activity, and pubertal status) contributed to predictive models of MRS and 8-iso, underscoring the impact healthy lifestyle behaviors may have, potentially even modifying perinatal programming. The unexpected lack of protection exerted by the Mediterranean diet in both mouse and human studies, suggests the beneficial effect observed in adults may not apply to perinatal exposure. Greater impact of HFDs in mice but BPA in humans highlights the need to carefully scrutinize findings before translating across species. Despite this difference, sex-specific effects occurred in both species, emphasizing the importance of investigating perinatal programming in all offspring. This research suggests that perinatal BPA and HFD exposure may be insufficient to induce perinatal programming of NAFLD. The significant impact of dam metabolic phenotype in mice and peripubertal behaviors in humans on metabolic and oxidative outcomes suggest NAFLD risk can be altered and potentially prevented at multiple life stages.
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Background: Overweight and abdominal obesity, in addition to medical conditions such as high blood pressure, high blood sugar and triglyceride levels, are typical risk factors associated with metabolic syndrome. Yet, considering the complexity of factors and underlying mechanisms leading to these inflammatory conditions, a deeper understanding of this area is still lacking. Some probiotics have a reputation of a relatively-long history of safe use, and an increasing number of studies are confirming benefits including anti-obesity effects when administered in adequate amounts. Recent reports demonstrate that probiotic functions may widely differ with reference to either intra-species or inter-species related data. Such differences do not necessarily reflect or explain strain-specific functions of a probiotic, and thus require further assessment at the intra-species level. Various anti-obesity clinical trials with probiotics have shown discrepant results and require additional consolidated studies in order to clarify the correct dose of application for reliable and constant efficacy over a long period. Methods: Three different strains of Lactobacillus sakei were administered in a high-fat diet induced obese murine model using three different doses, 1 × 1010, 1 × 109 and 1 × 108 CFUs, respectively, per day. Changes in body and organ weight were monitored, and serum chemistry analysis was performed for monitoring obesity associated biomarkers. Results: Only one strain of L. sakei (CJLS03) induced a dose-dependent anti-obesity effect, while no correlation with either dose or body or adipose tissue weight loss could be detected for the other two L. sakei strains (L338 and L446). The body weight reduction primarily correlated with adipose tissue and obesity-associated serum biomarkers such as triglycerides and aspartate transaminase. Discussion: This study shows intraspecies diversity of L. sakei and suggests that anti-obesity effects of probiotics may vary in a strain- and dose-specific manner.
Article
In 75% of women with polycystic ovary syndrome (PCOS), insulin action is impaired. In obesity, visceral adipose tissue becomes dysfunctional: Chronic inflammation is favored over storage, contributing to the development of metabolic complications. PCOS, metabolic syndrome (MetSy) and non-alcoholic fatty liver disease (NAFLD) apparently share common pathogenic factors; these include abdominal adiposity, excess body weight and insulin resistance. Alterations in the gut microbiome have been noted in women with PCOS compared to controls; these may lead to deterioration of the intestinal barrier, increased gut mucosal permeability and immune system activation, hyperinsulinemia and glucose intolerance, which hamper normal ovarian function and follicular development (all being hallmarks of PCOS). It has been proposed that PCOS may entail higher susceptibility to coronavirus disease 2019 (COVID-19) via its associated comorbidities (NAFLD, obesity, MetSy and alterations in the gut microbiome). Studies have found an association between acute respiratory distress syndrome (seen in severe cases of COVID-19) and the intestinal microbiome. Furthermore, apparently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can gain entry to the gastrointestinal tract via locally-expressed angiotensin converting enzyme type 2 receptors. Excess body weight is associated with more severe COVID-19 and increased mortality. Although robust links between SARS-CoV-2 infection and PCOS/NAFLD/gut microbiome/metabolic consequences are yet to be confirmed, it seems that strategies for adapting the intestinal microbiome could help reduce the severity of COVID-19 in women with PCOS with or without NAFLD, MetSy or obesity.
Chapter
Gut health refers to a number of physiological, microbiological, and physical functions that work together to maintain intestinal homeostasis. The gut provides a platform for the growth of a diverse microbiota that not only provides a barrier against colonization by pathogens but also regulates immune development and maturation and provides metabolites for host well-being. Disruption of the balance of gut microbiota is one of the major etiological factors associated with several gastrointestinal and infectious diseases, metabolic disorders such as obesity and diabetes, and inflammatory disease. Probiotics are live microbial supplements that beneficially affect the host by improving its intestinal microbial balance. This chapter summarizes the evidence available in literature for the beneficial effect of probiotics in modulating gut microbiota in favor of beneficial microbiota and then promoting host health. Considering the results of several investigations, probiotic consumption can affect the gut microbiota and gut barrier integrity, so the diseased state, caused due to gut microbiome imbalance, will regain homeostasis and health. Several mechanisms for probiotics’ actions are revealed; however, the gut microbiota modulatory effect is one of the main mechanisms through which the probiotics can affect the host. By knowing the benefits of gut microbiota balance, it would be wise to manipulate the composition of the gut microbiota through probiotic consumption.
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Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY...), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.
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The aim of this study was to determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents. Thirty-six adolescents (13-15 years), classified as overweight according to the International Obesity Task Force BMI criteria, were submitted to a calorie-restricted diet (10-40%) and increased physical activity (15-23 kcal/kg body weight/week) program over 10 weeks. Gut bacterial groups were analyzed by quantitative real-time PCR before and after the intervention. A group of subjects (n=23) experienced >4.0 kg weight loss and showed significant BMI (P=0.030) and BMI z-score (P=0.035) reductions after the intervention, while the other group (n=13) showed <2.0 kg weight loss. No significant differences in dietary intake were found between both groups. In the whole adolescent population, the intervention led to increased Bacteroides fragilis group (P=0.001) and Lactobacillus group (P=0.030) counts, and to decreased Clostridium coccoides group (P=0.028), Bifidobacterium longum (P=0.031), and Bifidobacterium adolescentis (P=0.044) counts. In the high weight-loss group, B. fragilis group and Lactobacillus group counts also increased (P=0.001 and P=0.007, respectively), whereas C. coccoides group and B. longum counts decreased (P=0.001 and P=0.044, respectively) after the intervention. Total bacteria, B. fragilis group and Clostridium leptum group, and Bifidobacterium catenulatum group counts were significantly higher (P<0.001-0.036) while levels of C. coccoides group, Lactobacillus group, Bifidobacterium, Bifidobacterium breve, and Bifidobacterium bifidum were significantly lower (P<0.001-0.008) in the high weight-loss group than in the low weight-loss group before and after the intervention. These findings indicate that calorie restriction and physical activity have an impact on gut microbiota composition related to body weight loss, which also seem to be influenced by the individual's microbiota.
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Immunological dysregulation is the cause of many non-infectious human diseases such as autoimmunity, allergy and cancer. The gastrointestinal tract is the primary site of interaction between the host immune system and microorganisms, both symbiotic and pathogenic. In this Review we discuss findings indicating that developmental aspects of the adaptive immune system are influenced by bacterial colonization of the gut. We also highlight the molecular pathways that mediate host-symbiont interactions that regulate proper immune function. Finally, we present recent evidence to support that disturbances in the bacterial microbiota result in dysregulation of adaptive immune cells, and this may underlie disorders such as inflammatory bowel disease. This raises the possibility that the mammalian immune system, which seems to be designed to control microorganisms, is in fact controlled by microorganisms.
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One of the most complex microbial ecosystems is represented by the microbiota of the human gastrointestinal tract (GIT). Although this microbial consortium has been recognized to have a crucial effect on human health, its precise composition is still not fully established. Among the GIT bacteria, bifidobacteria represent an important commensal group whose presence is often associated with health-promoting effects. In this work, we assessed the complexity of the human intestinal bifidobacterial population by analysing the diversity of several 16S rRNA gene-based libraries. These analyses showed the presence of novel bifidobacterial phylotypes, which had not been found earlier and may thus represent novel taxa within the genus Bifidobacterium.
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Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes.
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Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.
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The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
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The distal human intestine harbors trillions of microbes that allow us to extract calories from otherwise indigestible dietary polysaccharides. The products of polysaccharide fermentation include short-chain fatty acids that are ligands for Gpr41, a G protein-coupled receptor expressed by a subset of enteroendocrine cells in the gut epithelium. To examine the contribution of Gpr41 to energy balance, we compared Gpr41−/− and Gpr41+/+ mice that were either conventionally-raised with a complete gut microbiota or were reared germ-free and then cocolonized as young adults with two prominent members of the human distal gut microbial community: the saccharolytic bacterium, Bacteroides thetaiotaomicron and the methanogenic archaeon, Methanobrevibacter smithii. Both conventionally-raised and gnotobiotic Gpr41−/− mice colonized with the model fermentative community are significantly leaner and weigh less than their WT (+/+) littermates, despite similar levels of chow consumption. These differences are not evident when germ-free WT and germ-free Gpr41 knockout animals are compared. Functional genomic, biochemical, and physiologic studies of germ-free and cocolonized Gpr41−/− and +/+ littermates disclosed that Gpr41-deficiency is associated with reduced expression of PYY, an enteroendocrine cell-derived hormone that normally inhibits gut motility, increased intestinal transit rate, and reduced harvest of energy (short-chain fatty acids) from the diet. These results reveal that Gpr41 is a regulator of host energy balance through effects that are dependent upon the gut microbiota. • host-microbial interactions • energy balance • enteroendocrine cells • nutrient sensing • polysaccharide fermentation
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Results of experimental studies suggest that deviations in gut microbiota composition predispose to excessive energy storage and obesity. The mother influences the original inoculum and the development of infant microbiota, which in turn is associated with later weight gain. We characterized the gut microbiota in women according to their body mass index (BMI) and the effect of weight gain over pregnancy on the composition of microbiota before delivery. Overweight women (n = 18) were selected according to their prepregnancy BMI from a prospective follow-up study. Normal-weight women (n = 36) were selected as controls in consecutive order of recruitment. Excessive weight gain during pregnancy was defined as >16.0 kg for normal-weight and >11.5 kg for overweight states according to Institute of Medicine recommendations. The composition of gut microbiota was analyzed by fluorescent in situ hybridization coupled with flow cytometry (FCM-FISH) and by quantitative real-time polymerase chain reaction (qPCR). Bacteroides and Staphylococcus were significantly higher in the overweight state than in normal-weight women as assessed by FCM-FISH and qPCR. Mother's weight and BMI before pregnancy correlated with higher concentrations of Bacteroides, Clostridium, and Staphylococcus. Microbial counts increased from the first to third trimester of pregnancy. High Bacteroides concentrations were associated with excessive weight gain over pregnancy (P = 0.014). Gut microbiota composition and weight are linked, and mother's weight gain is affected by microbiota. Microbiota modification before and during pregnancy may offer new directions for preventive and therapeutic applications in reducing the risk of overweight and obesity.
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It has been proposed that the development of obesity in humans is influenced by the relative proportions of the two major phyla of bacteria (Bacteroidetes and Firmicutes) present in the large intestine. To examine the relationships between body mass index, weight loss and the major bacterial groups detected in fecal samples. Major groups of fecal bacteria were monitored using fluorescent in situ hybridization (FISH) in obese and non-obese subjects under conditions of weight maintenance, and in obese male volunteers undergoing weight loss on two different reduced carbohydrate weight-loss diets given successively for 4 weeks each. We detected no difference between obese and non-obese individuals in the proportion of Bacteroidetes measured in fecal samples, and no significant change in the percentage of Bacteroidetes in feces from obese subjects on weight loss diets. Significant diet-dependent reductions in a group of butyrate-producing Firmicutes were, however, detected in fecal samples from obese subjects on weight loss diets. Diets designed to achieve weight loss in obese subjects can significantly alter the species composition of the gut microbiota, but we find no evidence that the proportions of Bacteroidetes and Firmicutes among fecal bacteria have a function in human obesity.
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The human gastrointestinal tract is inhabited by a very diverse symbiotic microbiota, the composition of which depends on host genetics and the environment. Several studies suggested that the host genetics may influence the composition of gut microbiota but no genes involved in host control were proposed. We investigated the effects of the wild type and mutated alleles of the gene, which encodes the protein called pyrin, one of the regulators of innate immunity, on the composition of gut commensal bacteria. Mutations in MEFV lead to the autoinflammatory disorder, familial Mediterranean fever (FMF, MIM249100), which is characterized by recurrent self-resolving attacks of fever and polyserositis, with no clinical signs of disease in remission. A total of 19 FMF patients and eight healthy individuals were genotyped for mutations in the MEFV gene and gut bacterial diversity was assessed by sequencing 16S rRNA gene libraries and FISH analysis. These analyses demonstrated significant changes in bacterial community structure in FMF characterized by depletion of total numbers of bacteria, loss of diversity, and major shifts in bacterial populations within the Bacteroidetes, Firmicutes and Proteobacteria phyla in attack. In remission with no clinical signs of disease, bacterial diversity values were comparable with control but still, the bacterial composition was substantially deviant from the norm. Discriminant function analyses of gut bacterial diversity revealed highly specific, well-separated and distinct grouping, which depended on the allele carrier status of the host. This is the first report that clearly establishes the link between the host genotype and the corresponding shifts in the gut microbiota (the latter confirmed by two independent techniques). It suggests that the host genetics is a key factor in host-microbe interaction determining a specific profile of commensal microbiota in the human gut.
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New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host. • symbiosis • nutrient processing • energy storage • adiposity • fasting-induced adipose factor
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Evidence from in vivo and in vitro studies suggests that the consumption of pro- and prebiotics may inhibit colon carcinogenesis; however, the mechanisms involved have, thus far, proved elusive. There are some indications from animal studies that the effects are being exerted during the promotion stage of carcinogenesis. One feature of the promotion stage of colorectal cancer is the disruption of tight junctions, leading to a loss of integrity across the intestinal barrier. We have used the Caco-2 human adenocarcinoma cell line as a model for the intestinal epithelia. Trans-epithelial electrical resistance measurements indicate Caco-2 monolayer integrity, and we recorded changes to this integrity following exposure to the fermentation products of selected probiotics and prebiotics, in the form of nondigestible oligosaccharides (NDOs). Our results indicate that NDOs themselves exert varying, but generally minor, effects upon the strength of the tight junctions, whereas the fermentation products of probiotics and NDOs tend to raise tight junction integrity above that of the controls. This effect was bacterial species and oligosaccharide specific. Bifidobacterium Bb 12 was particularly effective, as were the fermentation products of Raftiline and Raftilose. We further investigated the ability of Raftilose fermentations to protect against the negative effects of deoxycholic acid (DCA) upon tight junction integrity. We found protection to be species dependent and dependent upon the presence of the fermentation products in the media at the same time as or after exposure to the DCA. Results suggest that the Raftilose fermentation products may prevent disruption of the intestinal epithelial barrier function during damage by tumor promoters.
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