No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects: The MaPLE randomised controlled trial
Abstract
Background & aim
Increased intestinal permeability (IP) can occur in older people and contribute to the activation of the immune system and inflammation. Dietary interventions may represent a potential strategy to reduce IP. In this regard, specific food bioactives such as polyphenols have been proposed as potential IP modulator due to their ability to affect several critical targets and pathways that control IP.
The trial aimed to test the hypothesis that a polyphenol-rich dietary pattern can decrease serum zonulin levels, an IP surrogate marker involved in tight junction modulation, and can beneficially alter the intestinal microbiota, and IP-associated biochemical and clinical markers in older subjects.
Methods
A randomised, controlled, cross-over intervention trial was performed. Sixty-six subjects (aged ≥ 60 y) with increased IP based on serum zonulin levels, were randomly allocated to one of the two arms of the intervention consisting of a control diet (C-diet) vs. a polyphenol-rich diet (PR-diet). Each intervention was 8-week long and separated by an 8-week wash out period. At the beginning and at the end of each intervention period, serum samples were collected for the quantification of zonulin and other biological markers. Faecal samples were also collected to investigate the intestinal microbial ecosystem. In addition, anthropometrical/physical/biochemical parameters and food intake were evaluated.
Results
Fifty-one subjects successfully completed the intervention and a high compliance to the dietary protocols was demonstrated. Overall, polyphenol intake significantly increased from a mean of 812 mg/day in the C diet to 1391 mg/day in the PR-diet. Two-way analysis of variance showed a significant effect of treatment (p = 0.008) and treatment x time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment x time interaction was observed showing a reduction of diastolic blood pressure (p = 0.028) following the PR-diet, which was strongest in those not using antihypertensive drugs. A decrease in both diastolic (p = 0.043) and systolic blood pressure (p = 0.042) was observed in women.
Interestingly, a significant increase in fiber-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium was observed following the PR intervention.
The efficacy of this dietary intervention was greater in subjects with higher serum zonulin at baseline, who showed more pronounced alterations in the markers under study. Furthermore, zonulin reduction was also stronger among subjects with higher body mass index and with insulin resistance at baseline, thus demonstrating the close interplay between IP and metabolic features.
Conclusions
These data show, for the first time, that a PR-diet can reduce serum zonulin levels, an indirect marker of IP. In addition, PR-diet reduced blood pressure and increased fiber-fermenting and butyrate-producing bacteria. These findings may represent an initial breakthrough for further intervention studies evaluating possible dietary treatments for the management of IP, inflammation and gut function in different target populations.
This study was registered at www.isrctn.org as
ISRCTN10214981.
... In the context of the MaPLE (Microbiome mAnipulation through Polyphenols for managing Leakiness in the Elderly) project, we have obtained significant findings that underline the complexity of evaluating intestinal permeability (IP) and the associated challenges. Our randomised controlled crossover intervention with a (poly) phenol-rich diet (PR-diet) demonstrated a reduction in serum zonulin levels, particularly in women and in subjects with high initial zonulin levels, who also experienced reductions in diastolic blood pressure and blood glucose levels [18]. Additionally, we observed a negative correlation between fiber-fermenting and butyrate-producing bacteria and markers of inflammation, indicating a link between gut bacterial composition and inflammatory status [18]. ...
... Our randomised controlled crossover intervention with a (poly) phenol-rich diet (PR-diet) demonstrated a reduction in serum zonulin levels, particularly in women and in subjects with high initial zonulin levels, who also experienced reductions in diastolic blood pressure and blood glucose levels [18]. Additionally, we observed a negative correlation between fiber-fermenting and butyrate-producing bacteria and markers of inflammation, indicating a link between gut bacterial composition and inflammatory status [18]. The PR-diet also significantly increased these beneficial bacteria, reinforcing the interaction between fiber, (poly)phenols, and gut microbiota activity [18]. ...
... Additionally, we observed a negative correlation between fiber-fermenting and butyrate-producing bacteria and markers of inflammation, indicating a link between gut bacterial composition and inflammatory status [18]. The PR-diet also significantly increased these beneficial bacteria, reinforcing the interaction between fiber, (poly)phenols, and gut microbiota activity [18]. Moreover, metabolites produced following the PR-diet intervention were inversely associated with serum zonulin levels, and we noted differences in (poly) phenol metabolism based on serum zonulin levels [19,20]. ...
Background
Older subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses.
Methods
A randomised, controlled, crossover study was performed involving 51 participants (≥ 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline.
Results
Among the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and bacterial DNAemia (16 S rRNA gene copies), with potential inflammatory-induced intestinal permeability. Differently, the other cluster had high levels of serum occludin, IL-6R, soluble intercellular adhesion molecule-1 (sICAM-1) and VEC, with potential inflammatory-induced endothelial dysfunction.
Conclusions
Overall, this study provides further support to the hypothesis that a (poly)phenol-rich diet may help to ameliorate intestinal permeability-associated conditions. In this regard, calprotectin might represent a promising biomarker since it is a protein that typically increases with age and it is considered indicative of intestinal and systemic inflammation. Further research is needed to develop targeted (poly)phenol-rich diets against age-related gut dysfunction and inflammation.
Trial registration
28/04/2017; ISRCTN10214981; https://doi.org/10.1186/ISRCTN10214981.
... Resveratrol's prebiotic and anti-inflammatory function has been demonstrated to contribute to the beneficial diversity of the GM by modulating the gut microenvironment and thereby strengthening the intestinal mucosal barrier [26,31]. Therefore, it is suggested that resveratrol primarily targets the gut microenvironment, including modulation of GM, thereby stimulating GM-derived metabolites such as SCFA [32] and also potent GM-derived resveratrol-metabolites, which might explain the numerous clinical benefits although resveratrol's oral bioavailability after metabolism in the gut and liver is only 1% [27]. ...
... The evidence for a modulation of the gut-bone axis comes primarily from population studies with specific dietary habits, such as the Western diet, a diet that correlates with dysbiosis and OP, whereas Mediterranean and anti-inflammatory diets are associated with healthier GM and reduced risk of OP [2]. The hypothesis is further supported by evidence that a polyphenol-rich diet with 1391 mg/day-including natural piceid and resveratrol from natural food such as cocoa powder and pomegranate juice -positively correlates with an increase in fiber-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium, indicating prebiotic effects [32] (Table 5). Likewise, another study confirmed that the dietary intake of polyphenols from red wine modulates GM demonstrating an increased abundance of Enterococcus, Prevotella, Bacteroides, Bifidobacterium, Bacteroides uniformis, Eggerthella lenta, and Blautia coccoides, Eubacterium rectale and the inhibition of pro-inflammatory GM species [253] (Table 5). ...
... Early clinical evidence confirms positive prebiotic effects such as an increase in Akkermansia muciniphila [257] (Table 5), known as a crucial bacteria for a healthy gut barrier [186]. Accordingly, a polyphenol-rich diet correlates with improved intestinal permeability as demonstrated by reduced serum zonulin levels among individuals aged ≥ 60 years, indicating an improved intestinal barrier [32]. ...
Osteoporosis (OP), which is characterized by a decrease in bone density and increased susceptibility to fractures, is closely linked to the gut microbiota (GM). It is increasingly realized that the GM plays a key role in the maintenance of the functioning of multiple organs, including bone, by producing bioactive metabolites such as short-chain fatty acids (SCFA). Consequently, imbalances in the GM, referred to as dysbiosis, have been identified with a significant reduction in beneficial metabolites, such as decreased SCFA associated with increased chronic inflammatory processes , including the activation of NF-κB at the epigenetic level, which is recognized as the main cause of many chronic diseases, including OP. Furthermore, regular or long-term medications such as antibiotics and many non-antibiotics such as proton pump inhibitors, chemotherapy, and NSAIDs, have been found to contribute to the development of dysbiosis, highlighting an urgent need for new treatment approaches. A promising preventive and adjuvant approach is to combat dysbiosis with natural polyphenols such as resveratrol, which have prebiotic functions and ensure an optimal microenvironment for beneficial GM. Resveratrol offers a range of benefits, including anti-inflammatory, anti-oxidant, analgesic, and prebiotic effects. In particular, the GM has been shown to convert resveratrol, into highly metabolically active molecules with even more potent beneficial properties, supporting a synergistic polyphenol-GM axis. This review addresses the question of how the GM can enhance the effects of resveratrol and how resveratrol, as an epigenetic modulator, can promote the growth and diversity of beneficial GM, thus providing important insights for the prevention and co-treatment of OP.
... Dietary factors may maintain or improve epithelial barrier structure and function, e.g. omega-3 PUFAs, fiber, vitamins and minerals, fermented foods and diets rich in polyphenols (21,95,109,116,117). Food processing may have deleterious effects on intestinal epithelial barrier through AGE formation and additives like emulsifiers (2,82,118). ...
... Beneficial effect on immune health and microbiome diversity (43,(87)(88)(89)(90)(91)(92) • Herbs and spices Provide polyphenols with anti-inflammatory effects (69,116,133) • Black and green tea Provide polyphenols with anti-inflammatory effects (69,116,133) ...
... Beneficial effect on immune health and microbiome diversity (43,(87)(88)(89)(90)(91)(92) • Herbs and spices Provide polyphenols with anti-inflammatory effects (69,116,133) • Black and green tea Provide polyphenols with anti-inflammatory effects (69,116,133) ...
The role of nutrition is increasingly recognized in the management of chronic immune diseases. However, the role of an immune‐supportive diet as adjuvant therapy in the management of allergic disease has not been similarly explored. This review assesses the existing evidence for a relationship between nutrition, immune function, and allergic disease from a clinical perspective. In addition, the authors propose an immune‐supportive diet to enhance dietary interventions and complementing other therapeutic options for allergic disease from early life to adulthood. A narrative review of the literature was conducted, to determine the evidence of the relationship between nutrition and immune function, overall health, epithelial barrier function, and gut microbiome, particularly in relation to allergy. Studies on food supplements were excluded. The evidence was assessed and utilized to develop a sustainable immune‐supportive diet to complement other therapies in allergic disease. The proposed diet consists of a highly diverse range of fresh, whole, and minimally processed plant‐based and fermented foods supplemented with moderate amounts of nuts, omega‐3‐rich foods and animal‐based products in proportional amounts of the EAT‐Lancet diet, such as (fatty) fish, (fermented) milk products which may be full‐fat and eggs, lean meat or poultry, which may be free‐range or organic.
... Higher adherence to MD is inversely associated with biomarkers of gastrointestinal mucosa permeability and with circulating LPS levels, in both adult subjects with chronic illnesses and older individuals [105,111,112]. These effects are emphasized with dietary interventions consisting in increased intake of (poly)phenol-rich foods, which are important components of MD [104,113,114]. In particular, the MaPLE randomized controlled trial showed that a (poly)phenol-rich food intervention in older subjects caused reduction in the serum levels of zonulin, associated with favorable changes in the gut microbiome including the increase of the relative abundance of F. prausnitzii [113]. ...
... These effects are emphasized with dietary interventions consisting in increased intake of (poly)phenol-rich foods, which are important components of MD [104,113,114]. In particular, the MaPLE randomized controlled trial showed that a (poly)phenol-rich food intervention in older subjects caused reduction in the serum levels of zonulin, associated with favorable changes in the gut microbiome including the increase of the relative abundance of F. prausnitzii [113]. Interestingly, these effects were less pronounced in those subjects with higher disruption of gut microbial community structure and with increased-intestinal permeability at baseline [104,114]. ...
Age-related changes in intestinal microbiome composition and function are increasingly recognized as pivotal in the pathophysiology of aging and are associated with the aging phenotype. Diet is a major determinant of gut-microbiota composition throughout the entire lifespan, and several of the benefits of a healthy diet in aging could be mediated by the microbiome. Mediterranean diet (MD) is a traditional dietary pattern regarded as the healthy diet paradigm, and a large number of studies have demonstrated its benefits in promoting healthy aging. MD has also a positive modulatory effect on intestinal microbiome, favoring bacterial taxa involved in the synthesis of several bioactive compounds, such as short-chain fatty acids (SCFAs), that counteract inflammation, anabolic resistance, and tissue degeneration. Intervention studies conducted in older populations have suggested that the individual response of older subjects to MD, in terms of reduction of frailty scores and amelioration of cognitive function, is significantly mediated by the gut-microbiota composition and functionality. In this context, the pathophysiology of intestinal microbiome in aging should be considered when designing MD-based interventions tailored to the needs of geriatric patients.
... In this context, energy restriction and healthy eating habits are the main strategies to reverse obesity and unbalances in intestinal health [13]. Weight loss and diets rich in fiber and polyphenols effectively reduce intestinal permeability, increasing the proportion of potentially beneficial bacteria and reducing inflammation [14][15][16][17]. In this sense, nuts are important sources of these nutrients, contribute to increased satiety, and exert a probiotic effect [18][19][20]. ...
... Both types of BN, cashew nuts and Brazil nuts, are rich sources of polyphenols, MUFA, n-3 series fatty acids, and fiber. These components contribute to reducing intestinal permeability and positively modulate the microbiota [9,14,15]. ...
... Here we used serum zonulin as a practical biomarker of intestinal permeability. 3,[24][25][26][27][28][29][30][31] Regarding the challenges in examining alterations before disease onset, there are few studies looking at predisease changes to intestinal permeability and none that we are aware of in subjects that develop CeD. 11,22 Here we were able to use data from the CD-GEMM study to find that intestinal permeability increased in the months to years before CDA. ...
... Intestinal permeability has been shown to be upregulated because of gut microbiome alterations in various disease states. 27,28,[31][32][33] Studies also show that zonulin levels are elevated in many diseases, such as CeD, T1D, Crohn's disease, metabolic dysfunction-associated liver disease, and obesity. 3,[34][35][36][37][38] Therefore, it is not surprising that we and others have previously found gut microbiota alterations in those with CeD and other autoimmune conditions. ...
OBJECTIVES
Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study’s objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability.
METHODS
We evaluated 102 children in the CDGEMM study from 2014–2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin.
RESULTS
Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6–78) preceding CDA compared to those without CDA (slope differential = β = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04).
CONCLUSIONS
Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.
... Otras recomendaciones identificadas, son las establecidas en la prevención de la demencia desde un enfoque de educación en consumo de alimentos fuentes de polifenoles que adicionalmente benefician la microbiota intestinal (35), así como implementar programas en promoción de la salud que incluyan evaluación de la adherencia a patrones dietéticos saludables, evaluación de la calidad de vida (47) y la evaluación de la calidad de la dieta por los índices alternativos de alimentación saludable (47,48). ...
Revisión Consejería nutricional en síndromes geriátricos en el adulto mayor: una revisión de literatura con miras a promover el envejecimiento saludable
Resumen
Fundamentos: La consejería nutricional en la promoción del envejecimiento saludable y prevención de los síndromes geriátricos, en un contexto de atención integral en un modelo de prevención se han relacionado con un impacto en la calidad de vida en pacientes de edad avanzada. En esta revisión se tuvo como objetivo recopilar evidencia científica sobre los factores para tener en cuenta en consejería nutricional en el adulto mayor para fomentar hábitos de alimentación saludable, de acuerdo con la Declaración Preferred Reporting Items in Systematic Reviews and Meta-Analyses PRISMA.
Métodos: La búsqueda se realizó en las bases de datos PubMed, ScienceDirect y Embase. Se incluyeron 30 artículos.
Resultados: La consejería nutricional en el adulto mayor aborda recomendaciones sobre alimentación saludable e hidratación, incluyendo alimentación y salud muscular, alimentación en salud mental y alimentación para prevenir la pérdida de peso y la desnutrición. Adicionalmente, recomienda realizar orientación nutricional a los adultos mayores y sus cuidadores en modificaciones dietarías en ingesta alta de alimentos para la prevención del sobrepeso, modificaciones dietarías en pérdida del apetito (anorexia del envejecimiento) y recomendaciones dietéticas para el tratamiento de la disfagia.
Conclusiones: En conclusión, la consejería nutricional para la promoción del envejecimiento saludable y prevención de los síndromes geriátricos en el adulto mayor debe ser comprendida como una intervención de salud pública que contribuye al desarrollo de programas integrales para apoyar un envejecimiento activo y saludable.
Summary
Background: Nutritional counseling in the promotion of healthy aging and prevention of geriatric syndromes, in a context of comprehensive care in a prevention model have been related to an impact on quality of life in elderly patients. The objective of this review was to compile scientific evidence on the factors to be taken into account in nutritional counseling in the elderly to promote healthy eating habits, according to the Preferred Reporting Items in Systematic Reviews and Meta-Analyses PRISMA Statement. Methods: The search was carried out in the databases PubMed, ScienceDirect and Embase. Results: hirty articles were included. Nutrition counseling in the older adult addresses recommendations on healthy eating and hydration, including nutrition and muscle health, nutrition in mental health, and nutrition to prevent weight loss and malnutrition. Additionally, it recommends nutritional counseling for older adults and their caregivers on dietary modifications for high food intake to prevent overweight, dietary modifications for loss of appetite (anorexia of aging) and dietary recommendations for the treatment of dysphagia. Conclusions: n conclusion, nutritional counseling for the promotion of healthy aging and prevention of geriatric syndromes in the elderly should be understood as a public health intervention that contributes to the development of comprehensive programs to support active and healthy aging.
... The well-known association between obesity and increased CRC risk 37 can at least in part be mediated by a gut barrier dysfunction and an altered gut microbiota. Dietary habits can influence that interaction, but intervention studies are not univocal to date in supporting the influence of dietary modifications on circulating zonulin levels [38][39][40] . Investigating (dietary) interventions targeting zonulin and bacterial translocation may offer promising avenues for personalized preventative strategies in individuals at high risk of CRC. ...
Intestinal permeability has been related to colorectal cancer (CRC) development. Zonulin, a protein able to regulate tight junction function and intestinal permeability, emerges as a promising marker to elucidate the contribution of bacterial translocation in CRC. An Italian case-control study included 77 CRC cases, 72 intestinal adenoma and 76 healthy controls (for a total of 148 tumor-free subjects), aged 20–85. Serum zonulin levels were quantified by ELISA kit and blood 16S rRNA gene copies by DNA extraction and polymerase chain reaction. We applied logistic regression models adjusted for center, sex, age and education. There was a positive association between zonulin and CRC risk. The odds ratio (OR) of CRC for the highest versus lowest tertile of zonulin as compared to tumor-free subjects was 2.36 (95% confidence interval, 1.14–4.86). The ORs were similar in colon and rectal cancers. The OR of colon cancer for the highest versus lowest levels of both zonulin and 16S rRNA gene copies was 4.55.
Circulating levels of zonulin were higher in CRC patients compared to tumor-free controls supporting the hypothesis of an interplay of gut barrier dysfunction and bacterial translocation in colorectal carcinogenesis. Zonulin may interact with 16S rRNA gene copies and serve as a further biomarker in the evaluation of CRC diagnosis.
... La zonulina es reconocida como una proteína que modula la permeabilidad entre las uniones estrechas del tracto gastrointestinal, colaborando a la salud intestinal y teniendo un papel importante en la disminución de translocación de bacterias y metabolitos que generan aumento en los procesos inflamatorios, lo cual toma importancia vital ante el sistema inmunológico envejecido del adulto mayor por una marcada disbiosis. 97 Lamentablemente no se cuenta con investigaciones mayores realizadas en humanos debido a que los métodos para valorar la calidad muscular y la presentación grasa requieren métodos invasivos como las biopsias. ...
Revisión multidisciplinaria sobre sarcopenia para contribuir a la difusión del tema en la comunidad clínica, promover el diagnóstico temprano, el tratamiento oportuno y su asociación con otras enfermedades
... In many diseases, including cirrhosis, disruption of intercellular tight junction proteins (including Occludin, Claudin, and ZO-1) increases intestinal permeability, allowing microbes to translocate from the intestinal lumen and causing subsequent inflammation and immune system activation. 3,4 IECs maintain the homeostasis of the intestinal epithelium by regulating cell death. Various programmed cell death mechanisms, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, play important roles in regulating the intestinal epithelium. ...
... The underlying mechanisms which result in frailty has been investigated in the non-HIV-infected population. Previous studies have revealed that impaired intestinal permeability (11,12) and the translocation of gut microbiota and products (13, 14) may possibly lead to an overall frail state over time. In 2017, Buford and colleagues confirmed that serum concentrations of zonulin and high-mobility group box protein (HMGB1) were 22% (p=0.005) and 16% (p=0.010) ...
Background
It has been previously demonstrated that intestinal barrier damage is one of the underlying mechanisms leading to frailty in non-HIV-infected aging populations. However, there is a paucity of direct evidence which demonstrates the association between intestinal barrier damage and frailty in people living with HIV (PLWH).
Methods
The present study is a retrospective case control study. Participants older than 50 years old were stratified into a frail/pre-frail group (case group) and non-frail group (control group) according to the Fried frailty phenotype. We collected and curated data concerning socio-demographic variables, psychological states and social functioning, and clinical information associated with the identification of biomarkers of intestinal barrier damage, microbial translocation, and levels of inflammatory cytokines of participants.
Results
The case group had significantly higher levels of Reg-3α (p=0.042) and I-FABP (p=0.045) compared to the control group. We further observed, after adjusting for confounding factors by logistic regression analysis, that I-FABP levels remained significantly higher in the case group compared to the control group (p=0.033). Also, Fried Phenotype scores positively correlated with I-FABP levels (rs=0.21, p=0.01), LPS levels (rs=0.20, p=0.02), and sCD14 levels (rs=0.18, p=0.04). Moreover, the study confirmed both the positive correlation between inflammatory cytokines (IL-6 and IP-10) with frailty in aging PLWH, and between inflammatory cytokines (IL-6, IL-8 and IP-10) with biomarkers of intestinal barrier dysfunction in older PLWH.
Conclusion
The present study indicates that the inflammation induced by intestinal barrier damage/dysfunction is likely to contribute to frailty in aging PLWH.
... A study involving the transplantation of fecal matter from a hypertensive donor into the intestines of mice demonstrated that the recipients exhibited elevated blood pressure [121]. A further study, a randomized controlled trial, demonstrated that a diet rich in polyphenols can significantly improve intestinal permeability in the elderly, increase the number of gut bacteria capable of digesting cellulose and producing butyrate, and reduce blood pressure [122]. In addition to gut microbiome dysbiosis, sleep disorders, including reduced quality and insufficient duration, also contribute to the occurrence of hypertension [123,124]. ...
Dietary components, including dietary fiber, unsaturated fatty acids, and polyphenols, along with meal timing and spacing, significantly affect the microbiota’s capacity to produce various metabolites essential for quality sleep and overall health. This review explores the role of gut microbiota in regulating sleep through various metabolites such as short-chain fatty acids, tryptophan, serotonin, melatonin, and gamma-aminobutyric acid. A balanced diet rich in plant-based foods enhances the production of these sleep-regulating metabolites, potentially benefiting overall health. This review aims to investigate how dietary habits affect gut microbiota composition, the metabolites it produces, and the subsequent impact on sleep quality and related health conditions.
... In addition, several flavonoids can protect striatal neurons, thereby ameliorating symptoms in HD models [191]. Moreover, polyphenol-rich dietary patterns counteract gut microbiota dysbiosis [192] and intestinal permeability [193], which is strictly associated with chronic activation of the immune system. Polyphenol compounds may exert neuroprotective actions after biotransformation by specific gut microbiome metabotypes and intestinal mucosa absorption [194], recently reviewed by Ticinesi et al. [195]. ...
Prominent pathological features of Huntington’s disease (HD) are aggregations of mutated Huntingtin protein (mHtt) in the brain and neurodegeneration, which causes characteristic motor (such as chorea and dystonia) and non-motor symptoms. However, the numerous systemic and peripheral deficits in HD have gained increasing attention recently, since those factors likely modulate disease progression, including brain pathology. While whole-body metabolic abnormalities and organ-specific pathologies in HD have been relatively well described, the potential mediators of compromised inter-organ communication in HD have been insufficiently characterized. Therefore, we applied an exploratory literature search to identify such mediators. Unsurprisingly, dysregulation of inflammatory factors, circulating mHtt, and many other messenger molecules (hormones, lipids, RNAs) were found that suggest impaired inter-organ communication, including of the gut–brain and muscle–brain axis. Based on these findings, we aimed to assess the risks and potentials of lifestyle interventions that are thought to improve communication across these axes: dietary strategies and exercise. We conclude that appropriate lifestyle interventions have great potential to reduce symptoms and potentially modify disease progression (possibly via improving inter-organ signaling) in HD. However, impaired systemic metabolism and peripheral symptoms warrant particular care in the design of dietary and exercise programs for people with HD.
... Microbial metabolism of polyphenols results in bioactive metabolites that exert physiological effects both systemically and locally at the intestinal mucosa [9,10]. Taken together, evidence suggests these mechanisms beneficially impact microbial community structure [11][12][13][14], intestinal permeability [15,16], oxidative stress [4,9,17], and inflammatory [9,[18][19][20], neurological [21][22][23], and cardiometabolic [24,25] processes. ...
While polyphenol consumption is often associated with an increased abundance of beneficial microbes and decreased opportunistic pathogens, these relationships are not completely described for polyphenols consumed via habitual diet, including culinary herb and spice consumption. This analysis of the International Cohort on Lifestyle Determinants of Health (INCLD Health) cohort uses a dietary questionnaire and 16s microbiome data to examine relationships between habitual polyphenol consumption and gut microbiota in healthy adults (n = 96). In this exploratory analysis, microbial taxa, but not diversity measures, differed by levels of dietary polyphenol consumption. Taxa identified as exploratory biomarkers of daily polyphenol consumption (mg/day) included Lactobacillus, Bacteroides, Enterococcus, Eubacterium ventriosum group, Ruminococcus torques group, and Sutterella. Taxa identified as exploratory biomarkers of the frequency of polyphenol-weighted herb and spice use included Lachnospiraceae UCG-001, Lachnospiraceae UCG-004, Methanobrevibacter, Lachnoclostridium, and Lachnotalea. Several of the differentiating taxa carry out activities important for human health, although out of these taxa, those with previously described pro-inflammatory qualities in certain contexts displayed inverse relationships with polyphenol consumption. Our results suggest that higher quantities of habitual polyphenol consumption may support an intestinal environment where opportunistic and pro-inflammatory bacteria are represented in a lower relative abundance compared to those with less potentially virulent qualities.
... According to a plethora of ongoing clinical reports and fundamental in vitro and in vivo studies, they evidently exert numerous biological activities that are vital to supporting normal metabolisms [3]. Furthermore, data analysis from epidemiological studies and associated meta-analyses have fundamental out comes that long term diets with rich natural polyphenols associated with some health promotive contribution and linked with the prevention against chronic diseases development such as cognitive defect [3] cardiovascular diseases in particular atherosclerosis [4,5], numerous cancer progression [6][7][8], osteoporosis [9,10], digestive system disorders [11,12], preventing overweight [13] and many crucial effects closely to the promotive status of human growth and general health. Therefore, it is critical for domestic policy that the governmental authority provide appropriate guidance on polyphenol quality in agricultural product treatments and processed food products. ...
Polyphenol groups have gained great interest as health-promoting and ailment-preventing agents in food ingredients. Their large range of distribution in the plant kingdom offers prospective development for many kinds of food products. From the beginning of the development processes, polyphenol group identity must be confirmed in order to guarantee the quality of their bioactivity, concentration consistency from batch to batch, and molecular stability. 1D and 2D nuclear magnetic resonance (NMR) provide robust and efficient finger printing of each polyphenol type at the skeleton level. Therefore, understanding the molecular skeleton of polyphenol types and their corresponding NMR typical signal has clearly become a necessity. However, for those in the initial involvement stage of polyphenol studies who do not possess adequate fundamental concepts in organic molecule structure, this will be a burdensome task. The goal of this review is to facilitate understanding how to use 1 H and 13 NMR spectra to figure out the type of polyphenol based on the type of skeleton derived from possible biosynthesis pathways. Since simple polyketide polyphenol groups are very rarely found in a settled group, shikimic acid-derived compounds such as hydroxy benzoic acid and ferulic acid become the entry point to insight into more complex groups: coumarin, lignan, diarylheptanoid, Anthraquinone, phloroglucinol, xanthonoid flavonoid, stilbenoid, glycosides, and combined polyphenols with terpenoids. 2D NMR methods, in particular COSY and HMBC spectra data, are highlighted for determining the attachment site of each skeleton identity. Flavonoid, lignan, and stilbenoid oligomer possibilities possessing spatial orientation are also featured.
... 92 A polyphenol-rich diet intervention for 8 weeks significantly reduced blood pressure and levels of serum zonulin, which is an intestinal permeability marker involved in tight junction modulation, in older adults, and induced significant increases in the abundance of butyrateproducing bacteria Butyricicocci and F. prausnitzii in the gut microbiome. 70 Additionally, these butyrateproducing bacteria were positively correlated with serum theobromine and methylxanthines derived from cocoa and/or green tea, and these metabolites were inversely correlated with serum zonulin. 71 These studies indicated that a polyphenol-rich diet may contribute to reinforcement of the intestinal barrier through increased butyrate and/or specific metabolites (owing to the resulting increase in the abundance of butyrate-producing bacteria). ...
As the proportion of older people in the world’s population steadily increases, there is an urgent need to identify ways to support healthy aging. The gut microbiome has been proposed to be involved in aging-related diseases and has become an attractive target for improving health in older people. Herein, we cover the relationship between the gut microbiome and chronological age in adults, and then, we discuss the gut microbiome features associated with frailty, as a hallmark of unhealthy aging in older people. Furthermore, we describe the effects of microbiome-targeted interventions, such as dietary patterns and consumption of probiotics, prebiotics, and synbiotics, on modulating the gut microbiome composition and further promoting healthy aging. Further studies are needed to explore the underlying mechanisms of gut microbiome-induced aging complications and to develop personalized microbiome-based strategies for reducing the severity of frailty or preventing the onset of frailty in older adults.
... In addition, an increase of intestinal permeability is also considered a potential factor induced by a series of intestinal diseases, such as inflammatory bowel disease, celiac disease, and irritable bowel syndrome (Bischoff et al., 2014). A MaPLE randomized controlled trial demonstrated that a polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels in older subjects (Del Bo et al., 2021). Another clinical trial also proved that increasing the consumption of polyphenol-rich food products could positively affect intestinal microbial ecosystem resulting in reduced intestinal permeability and decreased translocation of inflammogenic bacterial factors into the bloodstream (Guglielmetti et al., 2020). ...
Flavonoids are phytochemicals that widely exist in plants, fruits, and vegetables and have a variety of activities. However, due to their complex structure, it is often rarely absorbed into the blood. Intestinal bacteria regarded as the third kind of human organ have attracted extensive attention in recent years. Complex structural flavonoids can be catabolized into low molecular weight phenolic acids under the action of intestinal bacteria and then absorbed into the blood, showing several protective effects on the body. In addition, the intake of flavonoids can also regulate the composition and function of intestinal flora. This paper comprehensively summarizes the interaction between flavonoids and intestinal flora, as well as the impact on human health, in order to provide some insights on how to combine intestinal microorganisms to select and ingest dietary polyphenols for future applications in medicine. K E Y W O R D S clinical application , flavonoids, gut microbiota, mechanism, pharmacology
... An initial meeting (video-or teleconference) was conducted with a single investigator to confirm eligibility and explain study procedures prior to obtaining consent. Due to the lack of comparable studies to inform power calculations at the time the study commenced, a sample size of N ¼ 50 was chosen based on other diet and gut microbiota trials [19][20][21] and available resources. ...
Background:
Despite compositional alterations in gastrointestinal microbiota being purported to underpin some of the therapeutic effects of ginger, the effect of a standardized ginger supplement on gut microbiota has not been tested in humans.
Aims:
To determine the effect of a standardized ginger (Zingiber officinale) root powder, compared to placebo, on gastrointestinal bacteria and associated outcomes in healthy adults.
Methods:
A randomized double-blind placebo-controlled trial allocated participants aged 18-30-years to ginger or microcrystalline cellulose (MCC) placebo. The intervention comprised 1.2g/day of ginger (four capsules per day totaling 84mg/day of active gingerols/shogaols) for 14-days following a 1-week run-in period. Primary outcomes were gastrointestinal community composition, alpha and beta diversity, and differential abundance, measured using 16S rRNA gene sequencing of fecal samples. Secondary outcomes were gastrointestinal symptoms, bowel function, depression, anxiety, stress, fatigue, quality of life, and adverse events.
Results:
n=51 participants were enrolled and analyzed (71% female; mean age 25 [SD: 3] years; ginger: n=29, placebo: n=22). There was a greater increase in relative abundance of phylum, Actinobacteria, observed following ginger supplementation compared to placebo (U: 145.0; Z: -2.1; p=0.033). Ginger was associated with a greater abundance of the genera Parabacteroides, Bacillus, Ruminococcaceae incertae sedis, unclassified Bacilli, families Defluviitaleaceae, Morganellaceae, and Bacillaceae as well as lower abundance of the genus Blautia and family Sphingomonadaceae (p<0.05). An improvement in indigestion symptoms was observed with ginger supplementation (U:196.0; Z:-2.4; p=0.015). No differences between ginger and placebo groups were found for alpha and beta diversity nor other secondary outcomes. No moderate or severe adverse events were reported.
Conclusions:
Supplementation with ginger root powder was safe and altered aspects of the gastrointestinal bacteria composition; however, did not change alpha- or beta-diversity, bowel function, gastrointestinal symptoms, mood, or quality of life in healthy adults. These results provide further understanding regarding the mechanisms of action of ginger supplementation.
Trial registration:
Australia New Zealand Clinical Trials Registry (reference: ACTRN12620000302954p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379178&isReview=true) and the Therapeutic Goods Administration (reference: CT-2020-CTN-00380-1).
... 6,7 There is evidence that dietary ( poly)phenols (PPs) can contribute to reducing the impairment of IB and IP. 8,9 Recently, we have summarized the potential mechanisms through which PPs and their metabolites contribute to the control of IP. 10,11 In this regard, PPs may act at different levels of IB; first, by exerting a prebiotic effect by inhibiting the pathogenic bacteria and stimulating the growth of beneficial microbes. This modification in the gut microbiota composition, may reduce the production of endotoxins and stimulate the growth of shortchain fatty acid-producing bacteria able to prevent the translocation of pathogens and antigens. ...
Increasing evidence links the impairment of intestinal permeability (IP), a feature of the intestinal barrier, to numerous dysmetabolic and dysfunctional conditions. Several host and environmental factors, including dietary factors, can negatively and/or positively affect IP. In this regard, polyphenol-rich foods including berries have been proposed as potential IP modulators. However, the exact mechanisms involved are not yet fully elucidated. The aim of the present study was to evaluate the effect of a wild blueberry (WB; V. angustifolium) powder, naturally rich in polyphenols, to affect Caco-2 cell monolayer permeability and to identify the potential mechanisms in modulating the IP process. Caco-2 cells were incubated with TNF-α (10 ng mL-1), as a pro-inflammatory stimulus, and supplemented for 24 hours with different concentrations (1 and 5 mg mL-1) of WB powder. The integrity of the intestinal cell monolayer was evaluated by measuring the transepithelial electrical resistance (TEER) and the paracellular transport of FITC-dextran. In addition, the production of the tight junction proteins, such as claudin-1 and occludin, as well as protein carbonyl and 8-hydroxy 2 deoxyguanosine, as oxidative stress markers, were quantified in the supernatant by ELISA kits. Overall, the treatment with WB powder (5 mg mL-1) mitigated the loss of Caco-2 cell barrier integrity, as documented by an increase in TEER and a reduction in FITC values. This modulation was accompanied by an upregulation of claudin-1 and a reduction of 8-OHdG. Conversely, no effect was documented for the lower concentration (1 mg mL-1) and the other IP markers, as well as oxidative stress markers analysed. In conclusion, our findings suggest a potential role of WB in the modulation of cell barrier integrity. This modulation process could be attributed to an increase in claudin-1 expression and a reduction in 8-OHdG. Further studies should be performed to corroborate the results obtained. In addition, since the effects were observed at doses of WB achievable with the diet, these findings should be substantiated also through in vivo approaches.
... Microbiota-driven gut leakiness has also been implicated in the development of non-GI disorders, namely Parkinson's disease, Alzheimer's disease, and frailty [106,107]. An antioxidant diet may counteract these detrimental effects, being able to increase fiber-fermenting and butyrate-producing bacteria, such as the family Ruminococcaceae and the members of the genus Faecalibacterium, determining a decrease of zonulin expression, and thus a tighter intestinal barrier [108,109]. Consistently, the manipulation of the gut microbiota through Bifidobacterium adolescentis and Bifidobacterium lactis was found to reduce intestinal permeability in humans [110,111]. ...
The intestinal mucosa represents the most extensive human barrier having a defense function against microbial and food antigens. This barrier is represented externally by a mucus layer, consisting mainly of mucins, antimicrobial peptides, and secretory immunoglobulin A (sIgA), which serves as the first interaction with the intestinal microbiota. Below is placed the epithelial monolayer, comprising enterocytes and specialized cells, such as goblet cells, Paneth cells, enterochromaffin cells, and others, each with a specific protective, endocrine, or immune function. This layer interacts with both the luminal environment and the underlying lamina propria, where mucosal immunity processes primarily take place. Specifically, the interaction between the microbiota and an intact mucosal barrier results in the activation of tolerogenic processes, mainly mediated by FOXP3+ regulatory T cells, underlying intestinal homeostasis. Conversely, the impairment of the mucosal barrier function, the alteration of the normal luminal microbiota composition (dysbiosis), or the imbalance between pro- and anti-inflammatory mucosal factors may result in inflammation and disease. Another crucial component of the intestinal barrier is the gut-vascular barrier, formed by endothelial cells, pericytes, and glial cells, which regulates the passage of molecules into the bloodstream. The aim of this review is to examine the various components of the intestinal barrier, assessing their interaction with the mucosal immune system, and focus on the immunological processes underlying homeostasis or inflammation.
... Long-term polyphenyl-rich dietetic pattern has been proved to improve intestinal permeability and the level of inflammatory markers. 324 Previous studies have also proved that the intake of probiotics, such as Lactobacillus pentosus var. plantarum C29, has been proved to significantly reduce the level of systemic inflammatory factors and the expression of aging markers p16 and p53. ...
Aging is characterized by systemic chronic inflammation, which is accompanied by cellular senescence, immunosenescence, organ dysfunction, and age-related diseases. Given the multidimensional complexity of aging, there is an urgent need for a systematic organization of inflammaging through dimensionality reduction. Factors secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), promote chronic inflammation and can induce senescence in normal cells. At the same time, chronic inflammation accelerates the senescence of immune cells, resulting in weakened immune function and an inability to clear senescent cells and inflammatory factors, which creates a vicious cycle of inflammation and senescence. Persistently elevated inflammation levels in organs such as the bone marrow, liver, and lungs cannot be eliminated in time, leading to organ damage and aging-related diseases. Therefore, inflammation has been recognized as an endogenous factor in aging, and the elimination of inflammation could be a potential strategy for anti-aging. Here we discuss inflammaging at the molecular, cellular, organ, and disease levels, and review current aging models, the implications of cutting-edge single cell technologies, as well as anti-aging strategies. Since preventing and alleviating aging-related diseases and improving the overall quality of life are the ultimate goals of aging research, our review highlights the critical features and potential mechanisms of inflammation and aging, along with the latest developments and future directions in aging research, providing a theoretical foundation for novel and practical anti-aging strategies.
... One of the first proteins identified with promising results was zonulin (47 kDa), an acute phase reaction protein that controls intestinal permeability by inducing the disassembly of tight junctions; zonulin has been suggested as a biomarker of intestinal permeability, which can be measured in both blood and fecal samples [10]. In this regard, an intervention study (control diet vs. polyphenol-rich diet) conducted in 66 subjects (aged ≥ 60 years) with increased intestinal permeability based on the measurement of serum zonulin levels showed that zonulin reduction was greater among subjects with a higher body mass index and with insulin resistance at baseline, which demonstrated the close interplay between intestinal permeability and metabolic features [34]. However, recent studies have noted that the current commercially available assays do not detect only zonulin (prehaptoglobin-2) but rather quantify haptoglobin and complement factor C3 levels [35,36]. ...
The study of intestinal permeability is gaining growing interest due to its relevance in the onset and progression of several gastrointestinal and non-gastrointestinal diseases. Though the involvement of impaired intestinal permeability in the pathophysiology of such diseases is recognized, there is currently a need to identify non-invasive biomarkers or tools that are able to accurately detect alterations in intestinal barrier integrity. On the one hand, promising results have been reported for novel in vivo methods based on paracellular probes, i.e., methods that can directly assess paracellular permeability and, on the other hand, on fecal and circulating biomarkers able to indirectly assess epithelial barrier integrity and functionality. In this review, we aimed to summarize the current knowledge on the intestinal barrier and epithelial transport pathways and to provide an overview of the methods already available or currently under investigation for the measurement of intestinal permeability.
... Due to the prevalence of depression and the enormous economic burden it causes, it is crucial to evaluate risk factors, such as food. Recent epidemiological research has connected diet as a modifiable factor to oxidative stress [33][34][35], inflammation [36][37][38][39], as well as brain plasticity and function [40]. All of these factors have a substantial impact on an individual's mental health and the onset of depression [19]. ...
The role of diet is gaining attention among the modifiable factors associated with depression; thus, this case–control study examined the association between nutrition and depression in young Korean adults. Dietary surveys in individuals with depression (n = 39) and age- and gender-matched controls (n = 76) were conducted using food records and food frequency questionnaires. Men with depression consumed less mushrooms and meat, while women consumed significantly less grains (p < 0.05). Overall, the depression group consumed less energy and nutrients, and the difference was more pronounced in men. The male depression group had lower nutrient adequacy ratio (NAR) for energy, protein, vitamin A, thiamine, niacin, folate, and phosphorus, whereas the female depression group had lower NARs for energy, protein, niacin, and vitamin B12. The depression group had a significantly lower mean adequacy ratio in both genders. Furthermore, the proportion of inappropriate nutrient intake was higher in both genders of the depression group, exhibiting significant differences in energy, protein, niacin, folate, and zinc in men and energy, riboflavin, folate, and vitamin C in women. Hence, both men and women in the depression group had poor nutrient intake and high rates of nutrient inadequacy and improper consumption. This suggests that the quantity and quality of meals should be improved for individuals with depressive symptoms.
... Those results are consistent with our findings in which higher garlic consumption was associated with increased prevalence of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, belonging to Actinomycetia (formerly Actinobacteria) class, and with reduced abundance and prevalence of Family XI and Finegoldia genus, belonging to the Clostridia class and Clostridiales order. Referring to polyphenols, a RCT showed that polyphenol-rich dietary pattern reduced the serum levels of zonulin, which is considered a marker of intestinal permeability [36]. Moreover, quercetin is known for its anti-inflammatory, anticarcinogenic and anti-diabetic effect [37,38] and was able to reduce plasmatic methylglyoxal, a precursor of advanced glycation end products, in a RCT on 37 subjects [39]. ...
Purpose
Garlic consumption has been inversely associated to intestinal adenoma (IA) and colorectal cancer (CRC) risk, although evidence is not consistent. Gut microbiota has been implied in CRC pathogenesis and is also influenced by garlic consumption. We analyzed whether dietary garlic influence CRC risk and bacterial DNA in blood.
Methods
We conducted a case–control study in Italy involving 100 incident CRC cases, 100 IA and 100 healthy controls matched by center, sex and age. We used a validated food frequency questionnaire to assess dietary habits and garlic consumption. Blood bacterial DNA profile was estimated using qPCR and16S rRNA gene profiling. We derived odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of IA and CRC according to garlic consumption from multiple conditional logistic regression. We used Mann–Whitney and chi-square tests to evaluate taxa differences in abundance and prevalence.
Results
The OR of CRC for medium/high versus low/null garlic consumption was 0.27 (95% CI = 0.11–0.66). Differences in garlic consumption were found for selected blood bacterial taxa. Medium/high garlic consumption was associated to an increase of Corynebacteriales order, Nocardiaceae family and Rhodococcus genus, and to a decrease of Family XI and Finegoldia genus.
Conclusions
The study adds data on the protective effect of dietary garlic on CRC risk. Moreover, it supports evidence of a translocation of bacterial material to bloodstream and corroborates the hypothesis of a diet-microbiota axis as a mechanism behind the role of garlic in CRC prevention.
... In a stratification analysis by gender, this significant decrease was found only in women but not in men. 42 This study indicated that polyphenol-rich diet could improve intestinal permeability in the elderly. ...
Background and objectives:
Intestinal permeability (IP) is known to contribute to the immune system activation and inflammation; thus, it is proposed to have a role in the pathogenesis and exacerbation of many chronic diseases. Several studies have indicated that diet and nutritional status are risk factors for increased IP. In this mini review, we discussed the recent evidence on the association of diet, nutritional status, and intestinal permeability assessed by zonulin concentrations in serum and feces.
Methods and study design:
Literature searching was conducted in Pubmed, ProQuest and Google Scholar using the keywords "diet quality", "intestinal permeability", "nutritional status", and "zonulin" combined with Boolean operators "AND" and "OR".
Results:
Some studies indicated that intake of proper nutrition and good diet such as low total calorie intake, high intakes of omega-3 polyunsaturated fatty acids, fiber, vitamins, minerals, probiotics, and polyphenol-rich diet have significant impact on improvement of intestinal permeability marked by lower zonulin concentrations. Higher zonulin concentrations are found in those with overweight and obesity indicating that these population have increased IP. Most studies were conducted in adults and there are limited studies in children and adolescents. In addition, no studies have assessed diet quality to obtain a comprehensive picture on the complexities of diet in the population in relation to intestinal permeability.
Conclusions:
Diet and nutritional status are linked to zonulin concentrations, indicating a role in intestinal permeability. Further research should be conducted to investigate the relationship between diet quality, as measured by appropriate diet quality indices, and intestinal permeability in children, adolescents, and adults.
... This mechanism may improve the intestinal barrier by increasing the expression of tight junction proteins (ZO-1 and occludin) and mucin, and balancing the immune response interaction in the colon (200,201). In addition, polyphenols undergo extensive alterations in the gut microbiota, thus affecting the gut microbial ecosystem (201,202). In conclusion, these findings preliminarily reveal the complex relationship between dietary supplementation with polyphenols, intestinal barrier function, and metabolic diseases. ...
Physiologically, the intestinal barrier plays a crucial role in homeostasis and nutrient absorption and prevents pathogenic entry, harmful metabolites, and endotoxin absorption. Recent advances have highlighted the association between severely damaged intestinal barriers and diabetes, obesity, fatty liver, and cardiovascular diseases. Evidence indicates that an abated intestinal barrier leads to endotoxemia associated with systemic inflammation, insulin resistance, diabetes, and lipid accumulation, accelerating obesity and fatty liver diseases. Nonetheless, the specific mechanism of intestinal barrier damage and the effective improvement of the intestinal barrier remain to be explored. Here, we discuss the crosstalk between changes in the intestinal barrier and metabolic disease. This paper also highlights how to improve the gut barrier from the perspective of natural medicine, gut microbiota remodeling, lifestyle interventions, and bariatric surgery. Finally, potential challenges and prospects for the regulation of the gut barrier-metabolic disease axis are discussed, which may provide theoretical guidance for the treatment of metabolic diseases.
... Indigestible dietary fibers are commonly used as prebiotics, but other bioactive molecules, such as polyphenols, can also function as prebiotics to generate butyrate. Polyphenol intervention significantly increases the abundance of butyrate producers such as Faecalibacterium and members of the Ruminococcaceae family (Del Bo et al., 2021). Among other polyphenols, the impact of catechins, anthocyanins, and proanthocyanidins as prebiotics is more evident because they increase the abundance of Roseburia and Faecalibacterium spp. ...
Gut-microbial butyrate is a short-chain fatty acid (SCFA) of significant physiological importance than the other major SCFAs (acetate and propionate). Most butyrate producers belong to the Clostridium cluster of the phylum Firmicutes, such as Faecalibacterium, Roseburia, Eubacterium, Anaerostipes, Coprococcus, Subdoligranulum, and Anaerobutyricum. They metabolize carbohydrates via the butyryl-CoA: acetate CoA-transferase pathway and butyrate kinase terminal enzymes to produce most of butyrate. Although, in minor fractions, amino acids can also be utilized to generate butyrate via glutamate and lysine pathways. Butyrogenic microbes play a vital role in various gut-associated metabolisms. Butyrate is used by colonocytes to generate energy, stabilizes hypoxia-inducible factor to maintain the anaerobic environment in the gut, maintains gut barrier integrity by regulating Claudin-1 and synaptopodin expression, limits pro-inflammatory cytokines (IL-6, IL-12), and inhibits oncogenic pathways (Akt/ERK, Wnt, and TGF-β signaling). Colonic butyrate producers shape the gut microbial community by secreting various anti-microbial substances, such as cathelicidins, reuterin, and β-defensin-1, and maintain gut homeostasis by releasing anti-inflammatory molecules, such as IgA, vitamin B, and microbial anti-inflammatory molecules. Additionally, butyrate producers, such as Roseburia, produce anti-carcinogenic metabolites, such as shikimic acid and a precursor of conjugated linoleic acid. In this review, we summarized the significance of butyrate, critically examined the role and relevance of butyrate producers, and contextualized their importance as microbial therapeutics.
Gut barrier integrity is of fundamental importance for human health. Effects of flavan-3-ols, their metabolites, and their dietary sources in maintaining its functionality was analysed in this review.
The gut microbiome is amenable to dietary interventions, and polyphenol-rich diets have been shown to enhance abundances of bacteria associated with short-chain fatty acid (SCFA) production. We examined the effects of a strawberry-based intervention on the gut microbiome of 69 healthy elderly German adults. Participants in five groups consumed varying amounts of strawberries, freeze-dried strawberries, and capers in olive oil over 10 weeks as part of a randomized controlled trial. 16S rRNA sequencing was used to analyze differences in microbial composition, diversity, phenotypes, differential abundance, and functional pathways. The intervention group featuring the highest amounts of fresh and freeze-dried strawberries without capers in olive oil (group 4) showed changes in gut microbial diversity and differential abundance that could be linked to improved health. Beta diversity, based on weighted UniFrac distances, increased significantly ( P = 0.0035), potentially pathogenic bacteria decreased ( P = 0.04), and abundances of SCFA-producing genera Faecalibacterium and Prevotella increased significantly. Other findings included a significant reduction of CAG-352 , Preveotellaceae_NK3B31-group , and Eubacterium coprostanoligenes (group 2), and a trend of lowered Firmicutes-to-Bacteroidetes ratio ( P = 0.067) and a reduction in Ruminococcaceae (group 3). Our findings suggest that a dietary intervention based on strawberries can positively alter the gut microbiota of healthy elderly people as seen in an enrichment of SCFA-producing genera, increased diversity, and a reduction in potentially pathogenic bacteria.
IMPORTANCE
Aging is often associated with changes in the gut microbiome, including a decline in beneficial bacteria and an increase in potentially pathogenic species. Addressing these changes through lifestyle interventions is of significant interest. Our study demonstrates that a 10-week dietary intervention with strawberries can beneficially modulate gut microbial composition and diversity in healthy elderly individuals. Notably, the group consuming the highest amount of strawberries (without capers in olive oil) initially had higher abundances of potentially pathogenic bacteria. Here, the intervention led to increased abundances of the beneficial genera Faecalibacterium and Prevotella , which are linked to health benefits including reduced inflammation and improved lipid metabolism. These findings suggest that strawberry consumption can positively influence gut microbial composition, thereby contributing to overall health and disease prevention in older adults.
Background
Hypertension is a prevalent and complex disease that is increasingly recognized to be influenced by the gut microbiome and its metabolites. Understanding the relationship between gut microbial metabolites and blood pressure regulation could provide new therapeutic avenues.
Main body
This review examines the role of key microbial metabolites—short-chain fatty acids, trimethylamine N-oxide, tryptophan derivatives, polyamines, bile acids, and phenylacetylglutamine—in blood pressure regulation. Short-chain fatty acids, produced through dietary fiber fermentation, can lower blood pressure by modulating immune responses and reducing inflammation. Elevated trimethylamine N-oxide levels are associated with increased cardiovascular risk and hypertension, influencing cholesterol metabolism and promoting atherosclerosis. Tryptophan derivatives interact with vascular and renal functions to modulate blood pressure. Polyamines affect blood pressure regulation through their impact on nitric oxide synthesis and vascular tone. Bile acids influence blood pressure via gut microbiota modulation and activation of metabolic receptors. Phenylacetylglutamine has been linked to hypertension through its effects on platelet hyperactivity and thrombosis. Therapeutic approaches targeting these metabolites, including probiotics, prebiotics, fecal microbiota transplantation, dietary interventions, and polyphenols, have shown varying degrees of success. Probiotics and prebiotics promote the growth of beneficial gut bacteria and may lower blood pressure. Dietary interventions, such as the Mediterranean diet, positively affect blood pressure and cardiovascular health by modulating the gut microbiota. Polyphenols, known for their antioxidant properties, are associated with blood pressure reductions and improved vascular function. Fecal microbiota transplantation shows promise in restoring gut microbial balance and improving metabolic health, potentially influencing blood pressure regulation.
Conclusion
The review highlights the significant role of gut microbial metabolites in regulating blood pressure, offering new avenues for hypertension management. Key metabolites, including short-chain fatty acids, trimethylamine N-oxide, and bile acids, play critical roles in blood pressure modulation. Therapeutic strategies targeting these metabolites, such as probiotics, prebiotics, and dietary interventions, hold promise, though further research is needed to fully understand their mechanisms and optimize their use. Advancing microbiota-based interventions through large-scale studies and exploring personalized therapies will be essential for developing effective treatments in hypertension management.
Background: Aging is a natural biological process influenced by multiple factors and is a significant contributor to various chronic diseases. Slowing down the aging process and extending health span have been pursuits of the scientific field. Methods: Examination of the effects of dietary polyphenols on hallmarks of aging such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. Results: Polyphenols, abundant in nature, exhibit numerous biological activities, including antioxidant effects, free radical scavenging, neuroprotection, and anti-aging properties. These compounds are generally safe and effective in potentially slowing aging and preventing age-related disorders. Conclusions: The review encourages the development of novel therapeutic strategies using dietary polyphenols to create holistic anti-aging therapies and nutritional supplements.
Objective:
Polyphenols are organic compounds with diverse biological activities such as anti-inflammatory and antioxidant effects, making them important candidates for the development of anti-aging drugs. In this systematic review, we aimed to answer the question: can plant-derived polyphenols have an immunomodulatory effect in experimental models of aging?
Methods:
We systematically searched Web of Science, MEDLINE/Pubmed, and Embase to select articles using the following combinations of terms and synonyms: polyphenols, phenols, senescence, aging, and immune. The selected articles were evaluated for reporting quality and risk-of-bias according to standard guidelines.
Results:
The most used polyphenol was resveratrol, followed by curcumin, salidroside, and gallic acid. These molecules demonstrated an ability to restore immune function both in vitro and in vivo. The mechanism of action was not completely elucidated in these studies, but inhibition of NF-kB signaling, and antioxidant properties seemed to account for the anti-aging effects. All articles included in the review had good quality of reporting but failed to describe an adequate sample size, criteria for inclusion/exclusion, randomization, and blinding.
Conclusion:
We conclude that polyphenols are promising immunomodulatory substances for use in anti-aging therapies. However, more research with standardized analysis is needed to understand the role of these molecules in the prevention or reduction of damage associated with the aging process, as well as to determine the safety profile and consequences of systemic action.
Background
HIV-associated neurocognitive disorders (HAND) still affects persons living with HIV (PLWH) and their pathogenesis isn’t completely understood. We aimed to explore the association between plasma and CSF markers of blood-brain barrier (BBB) impairment and HAND in untreated PLWH.
Design
Cross-sectional study.
Methods
We enrolled untreated PLWH, who underwent blood exams and lumbar puncture to measure inflammation (IL-15, TNF-α), BBB damage (zonulin and tight junction proteins, TJs: occludin, claudin-5) and endothelial adhesion molecules (VCAM-1, ICAM-1). A comprehensive neurocognitive battery was used to diagnose HAND (Frascati criteria).
Results
Twenty-one patients (21/78, 26,9%) patients presented HAND (100% ANI). HAND patients displayed more frequently non-CNS AIDS-defining conditions, lower nadir CD4+ T-cells and increased CD4+ T-cell exhaustion (lower CD4+CD127+ and CD4+CD45RA+ T cells percentages), in comparison to subjects without cognitive impairment. Furthermore, HAND was characterized by higher plasma inflammation (IL-15), but lower CSF levels of biomarkers of BBB impairment (zonulin and occludin). The association between BBB damage with HAND was confirmed by fitting a multivariable logistic regression. CSF/plasma endothelial adhesion molecules weren’t associated with HAND, but with a poor performance in different cognitive domains.
Conclusions
By showing heightened inflammation and BBB impairment, our study suggests loss of BBB integrity as a possible factor contributing to the development of HAND in untreated PLWH.
Long COVID (LC) refers to continuing conditions following acute COVID-19 infection, lasting for weeks to months. It affects a wide range of people's lives, including physical, physiological, and social-economic aspects. Hence, leads to lowering quality of life and other future health challenges worldwide. Health problems following the acute phase of COVID-19 may persist or appear for days to months after the acute infection is resolved. The phenotype of long COVID-19 commonly manifests as a collection of symptoms such as muscle weakness, neuro-cognitive alteration, and respiratory disturbances. Mechanisms underpinning long COVID-19 are still not fully understood. It is hypothesized that inflammation plays a crucial role in LC development through several complex pathways. Recently, effective treatments for long COVID-19 have not been established. Its management depends on the patient's symptoms and needs. Nutritional modulation and physical rehabilitation are advised for long-COVID-19 improvement and increased quality of life. The Mediterranean diet (Med-diet) has been acknowledged for its impact on health through its antioxidant and anti-inflammatory effects. Bioactive compounds in Med-diet have been widely studied to reduce oxidative stress and inflammation in cells. Adherence to Med-diet food intake is linked to a lower incidence of obesity, cancer, cardiovascular disease, and metabolic disease. Therefore, the potential effect of Med-diet as a nutritional approach for long-COVID-19 treatment and prevention will be summarized.
Birch wood-derived fiber extracts containing glucuronoxylans (GX) and polyphenols show potential for various food technological applications. This study investigated the effect of two extracts, GXpoly and pureGX, differing in lignin content on colonic barrier function. Healthy rats were fed diets containing 10% GXpoly, pureGX, or cellulose for 4 weeks. Colon crypt depth was lower in the GX groups than in the control group, but in the proximal colon, the result was significant only in GXpoly. An artificial intelligence approach was established to measure the mucus content and goblet cells. In the distal colon, their amounts were higher in the control group than in the GX groups. All diets had a similar effect on the expression of the tight junction proteins occludin, claudin-1, and claudin-7. GXpoly enhanced the fecal IgA production. Our results suggest that GX-rich extracts could support the colonic barrier and work as functional food ingredients in the future.
Purpose
Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity).
Methods
The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings.
Results
Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses.
Conclusions
Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.
Reactive oxygen species (ROS) are the initiators in foods and in the stomach of oxidized dietary lipids, proteins, and lipid-oxidation end-products (ALEs), inducing in humans the development of several chronic diseases and cancer. Epidemiological, human clinical and animal studies supported the role of dietary polyphenols and derivatives in prevention of development of such chronic diseases. There is much evidence that polyphenols/derivatives at the right timing and concentration, which is critical, acts mostly in the aerobic stomach and generally in the gastrointestinal tract as reducing agents, scavengers of free radicals, trappers of reactive carbonyls, modulators of enzyme activity, generators of beneficial gut microbiota and effectors of cellular signaling. In the blood system, at low concentration, they act as generators of electrophiles and low concentration of H2O2, acting mostly as cellular signaling, activating the PI3K/Akt-mediated Nrf2/eNOS pathways and inhibiting the inflammatory transcription factor NF-κB, inducing the cells, organs and organism for eustress, adaptation and surviving.
The Folin-Ciocalteu method is a well-established and widely used assay for measuring total (poly)phenol content in food/plant products. In recent years, there has been growing interest in applying this method to human samples due to its simplicity and efficacy. However, biological matrices such as blood and urine contain several interference substances that must be eliminated beforehand. This mini-review summarizes the current state of knowledge regarding the use of the Folin-Ciocalteu assay to measure total phenolic content in human urine and blood samples, as well as the preceding cleaning methods to remove interferences. Higher total (poly)phenol levels measured by the Folin-Ciocalteu method have been associated with a decrease in mortality and several risk variables. We focus on the application of this sustainable assay as a biomarker of poly(phenol) intake and its potential use as an anti-inflammatory biomarker in clinical laboratories. The Folin-Ciocalteu method, with a clean-up extraction step, is a reliable tool for determining total (poly)phenol consumption. Here, we also recommend using the Folin-Ciocalteu assay as means to measure anti-inflammatory activity.
Since the gut microbiota plays a pivotal role in host homeostasis and energy balance, changes in its composition can be associated with disease states through the promotion of immune-mediated inflammatory disorders and increasing intestinal permeability, ultimately leading to the impairment of intestinal barrier function. Za’atar is one of the most popular plant-based foods in the Eastern Mediterranean region. Za’atar is a mixture of different plant leaves, fruits, and seeds and contains hundreds of antioxidant compounds, especially polyphenols, and fiber, with pre-clinical and clinical evidence suggesting health-promoting effects in cardiovascular and metabolic disease. Za’atar compounds have also been studied from a gastrointestinal perspective, concerning both gut microbiota and gastrointestinal diseases. Antioxidants such as Za’atar polyphenols may provide beneficial effects in the complex interplay between the diet, gut microbiota, and intestinal permeability. To our knowledge, no studies have reported the effects of the whole Za’atar mixture, however, based on the pre-clinical studies published on components and single compounds found in Za’atar, we provide a clinical overview of the possible effects on the gastrointestinal tract, focusing mainly on carvacrol, rosmarinic acid, gallic acid, and other polyphenols. We also cover the potential clinical applications of Za’atar mixture as a possible nutraceutical in disorders involving the gastrointestinal tract.
Alistipes is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the Bacteroidetes phylum, which are highly relevant in dysbiosis and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 species: Alistipes finegoldii, Alistipes putredinis, Alistipes onderdonkii, Alistipes shahii, Alistipes indistinctus, Alistipes senegalensis, Alistipes timonensis, Alistipes obesi, Alistipes ihumii, Alistipes inops, Alistipes megaguti, Alistipes provencensis, and Alistipes massiliensis. Alistipes communis and A. dispar, and the subspecies A. Onderdonkii subspecies vulgaris (vs. onderdonkii subsp.) are the newest strains featured outside that list. Although typically isolated from the human gut microbiome various species of this genus have been isolated from patients suffering from appendicitis, and abdominal and rectal abscess. It is possible that as Alistipes spp. emerge, their identification in clinical samples may be underrepresented as novel MS-TOF methods may not be fully capable to discriminate distinct species as separate since it will require the upgrading of MS-TOF identification databases. In terms of pathogenicity, there is contrasting evidence indicating that Alistipes may have protective effects against some diseases, including liver fibrosis, colitis, cancer immunotherapy, and cardiovascular disease. In contrast, other studies indicate Alistipes is pathogenic in colorectal cancer and is associated with mental signs of depression. Gut dysbiosis seems to play a role in determining the compositional abundance of Alistipes in the feces (e.g., in non-alcoholic steatohepatitis, hepatic encephalopathy, and liver fibrosis). Since Alistipes is a relatively recent sub-branch genus of the Bacteroidetes phylum, and since Bacteroidetes are commonly associated with chronic intestinal inflammation, this narrative review illustrates emerging immunological and mechanistic implications by which Alistipes spp. correlate with human health.
Background:
During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role.
Methods:
MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stress, gut and blood microbiomics, metabolomics. A sample size of 50 subjects was defined based on IP as primary outcome.
Discussion:
Evidence that increasing the consumption of polyphenol-rich food products can positively affect intestinal microbial ecosystem resulting in reduced IP and decreased translocation of inflammogenic bacterial factors into the bloodstream will be provided. The integration of data from gut and blood microbiomics, metabolomics and other IP-related markers will improve the understanding of the beneficial effect of the intervention in the context of polyphenols-microbiota-IP interactions. Finally, findings obtained will provide a proof of concept of the reliability of the dietary intervention, also contributing to future implementations of dietary guidelines directed to IP management in the older and other at risk subjects.
Trial registration:
The trial is registered at (ISRCTN10214981); April 28, 2017.
The formulation of next-generation probiotics requires competent preclinical studies to show their efficacy and safety status. This study aims to confirm the safety of the prolonged oral use of Bacteroides uniformis CECT 7771, a strain that protected against metabolic disorders and obesity in preclinical trials, in a sub-chronic 90 day trial in animals. The safety assessment was conducted in male and female Wistar rats (n = 50) administered increasing doses (10 8 CFU/day, 10 9 CFU/day, or 10 10 CFU/day) of B. uniformis CECT 7771, 10 10 CFU/day of B. longum ATCC 15707 T , which complies with the qualifying presumption of safety (QPS) status of the EU, or vehicle (placebo), as the control. Pancreatic, liver, and kidney functions and cytokine concentrations were analyzed. Bacterial translocation to peripheral tissues was evaluated, and colon integrity was investigated histologically. No adverse metabolic or tissue integrity alterations were associated with treatments; however, alanine aminotransferase levels and the ratio of anti-inflammatory to pro-inflammatory cytokines in serum indicated a potentially beneficial role of B. uniformis CECT 7771 at specific doses. Additionally, the microbial community structure was modified by the interventions, and potentially beneficial gut bacteria were increased. The results indicated that the oral consumption of B. uniformis CECT 7771 during a sub-chronic 90 day study in rats did not raise safety concerns.
The term inflammaging is now widely used to designate the inflammatory process of natural aging. During this process, cytokine balance is altered, presumably due to the loss of homeostasis, thus contributing to a greater predisposition to disease and exacerbation of chronic diseases. The aim of the study was to analyze the relationship between pro-inflammatory markers and age in the natural aging process of healthy individuals. One hundred and ten subjects were divided into 5 groups according to age (22 subjects/group). Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were quantified using the ELISA method. High-sensitivity C-reactive protein (hsCRP) was analyzed by turbidimetry according to laboratory procedures. The main findings of this study were: a positive correlation between hsCRP and IL-6 as a function of age (110 subjects); women showed stronger correlations; the 51-60 age group had the highest values for hsCRP and IL-6; women presented higher values for hsCRP in the 51-60 age group and higher values for IL-6 in the 61-70 age group; and men showed higher values in the 51-60 age group for hsCRP and IL-6. In conclusion, the natural aging process increased IL-6 and hsCRP levels, which is consistent with the inflammaging theory; however, women presented stronger correlations compared to men (IL-6 and hsCRP) and the 51-60 age range seems to be a key point for these increases. These findings are important because they indicate that early preventive measures may minimize the increase in these inflammatory markers in natural human aging.
Intestinal barrier function is suggested to decrease with aging and may be improved by pectin intake. The aim of this study was to investigate the effects of four weeks pectin supplementation on gastrointestinal barrier function in vivo and ex vivo in different age groups. In a randomized, double-blind, placebo-controlled, parallel study, 52 healthy young adults (18–40 years) and 48 healthy elderly (65–75 years) received 15 g/day pectin or placebo for four weeks. Pre- and post-intervention, in vivo gastrointestinal permeability by a multisugar test, and defense capacity in mucosal samples were assessed. Sigmoid biopsies were collected post-intervention from subgroups for Ussing chamber experiments and gene transcription of barrier-related genes. Pectin intervention did not affect in vivo gastroduodenal, small intestinal, colonic, and whole gut permeability in young adults nor in elderly (p ≥ 0.130). Salivary and fecal sIgA and serum IgA were not significantly different between pectin versus placebo in both age groups (p ≥ 0.128). In both young adults and elderly, no differences in transepithelial electrical resistance and fluorescein flux (p ≥ 0.164) and relative expression of genes analyzed (p ≥ 0.222) were found between pectin versus placebo. In conclusion, intestinal barrier function was not affected by four weeks pectin supplementation neither in healthy young adults nor in healthy elderly.
The intestinal tract is the largest barrier between a person and the environment. In this role, the intestinal tract is responsible not only for absorbing essential dietary nutrients, but also for protecting the host from a variety of ingested toxins and microbes. The intestinal barrier system is composed of a mucus layer, intestinal epithelial cells (IECs), tight junctions (TJs), immune cells, and a gut microbiota, which are all susceptible to external factors such as dietary fats. When components of this barrier system are disrupted, intestinal permeability to luminal contents increases, which is implicated in intestinal pathologies such as inflammatory bowel disease, necrotizing enterocolitis, and celiac disease. Currently, there is mounting evidence that consumption of excess dietary fats can enhance intestinal permeability differentially. For example, dietary fat modulates the expression and distribution of TJs, stimulates a shift to barrier-disrupting hydrophobic bile acids, and even induces IEC oxidative stress and apoptosis. In addition, a high-fat diet (HFD) enhances intestinal permeability directly by stimulating proinflammatory signaling cascades and indirectly via increasing barrier-disrupting cytokines [TNFα, interleukin (IL) 1B, IL6, and interferon γ (IFNγ)] and decreasing barrier-forming cytokines (IL10, IL17, and IL22). Finally, an HFD negatively modulates the intestinal mucus composition and enriches the gut microflora with barrier-disrupting species. Although further research is necessary to understand the precise role HFDs play in intestinal permeability, current data suggest a stronger link between diet and intestinal disease than was first thought to exist. Therefore, this review seeks to highlight the various ways an HFD disrupts the gut barrier system and its many implications in human health.
Growing evidence support association between polyphenol intake and reduced risk for chronic diseases, even if there is a broad debate about the effective amount of polyphenols able to exert such protective effect. The present systematic review provides an overview of the last 10-year literature on the evaluation of polyphenol intake and its association with specific disease markers and/or endpoints. An estimation of the mean total polyphenol intake has been performed despite the large heterogeneity of data reviewed. In addition, the contribution of dietary sources was considered, suggesting tea, coffee, red wine, fruit and vegetables as the main products providing polyphenols. Total flavonoids and specific subclasses, but not total polyphenols, have been apparently associated with a low risk of diabetes, cardiovascular events and all-cause mortality. However, large variability in terms of methods for the evaluation and quantification of polyphenol intake, markers and endpoints considered, makes it still difficult to establish an evidence-based reference intake for the whole class and subclass of compounds. Nevertheless, the critical mass of data available seem to strongly suggest the protective effect of a polyphenol-rich dietary pattern even if further well targeted and methodologically sound research should be encouraged in order to define specific recommendations.
Background:
Dietary polyphenols, including flavonoids, have been the focus of major recent attentions due to their wide content in a variety of foods commonly consumed and the findings from numerous studies showing evidence of an association with positive outcomes on human health.
Methods:
A systematic search using electronic databases PubMed and EMBASE was performed to retrieve English language studies published from the earliest indexing year of each database to April 2019, reporting on the association between dietary flavonoids intake and hypertension.
Results:
The search strategy resulted in the final selection of 20 studies including 15 cross-sectional investigations and 7 prospective cohorts (1 study reported on 3 prospective cohorts). 5 prospective cohorts, comprising 200,256 individuals and 45,732 cases of hypertension were included in the quantitative analysis. Analysis by extreme quantiles of intake of flavonoid showed a non-significant association with decreased risk of hypertension (RR (risk ratio): 0.96, 95% CI (confidence interval): 0.89, 1.03). Taking into consideration individual flavonoid subclasses, dietary anthocyanins intake was associated with 8% reduction in risk of hypertension, when comparing highest vs. lowest exposure (RR: 0.92, 95% CI: 0.88, 0.97).
Conclusions:
Further studies are needed to strengthen the retrieved association between anthocyanins consumption and decreased risk of hypertension and clarify whether total flavonoids or rather individual subclasses may exert beneficial effects on blood pressure.
Background
Anthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations.
Objective
In the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome.
Methods
A double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.2 ± 3.0 kg/m²) was conducted, which fed 2 dietarily achievable blueberry intakes [equivalent to 1/2 and 1 cup/d (75/150 g)] compared with matched placebo. Insulin resistance was assessed via the homeostasis model assessment of insulin resistance (primary endpoint) and confirmed by [6-6-²H2]-glucose-labeled, 2-step hyperinsulinemic clamp (n = 20). Clinically relevant cardiometabolic endpoints [including flow-mediated dilatation, augmentation index, lipoprotein status (by nuclear magnetic resonance spectroscopy), and nitric oxide (NO)-related metabolite assay] and anthocyanin metabolism were assessed.
Results
A daily intake of 1 cup of blueberries improved endothelial function (flow-mediated dilatation: +1.45%; 95% CI: 0.83%, 2.1%; P = 0.003), systemic arterial stiffness (augmentation index: –2.24%; 95% CI: –3.97%, –0.61%; P = 0.04) and attenuated cyclic guanosine monophosphate concentrations. In statin nonusers (n = 71), elevated high-density lipoprotein cholesterol (+0.08 mmol/L; P = 0.03), high-density lipoprotein particle density (+0.48n, ×10–6; P = 0.002) and apolipoprotein A-I (+0.05 g/L; P = 0.01) concentrations were observed following the 1-cup/d intervention. Treatment compliance was 94.1% (wrapper returns) and total concentrations of anthocyanin-derived phenolic acid metabolites significantly increased, dose-dependently, in serum and 24-h urine (P < 0.01 and P < 0.001, respectively). Insulin resistance, pulse wave velocity, blood pressure, NO, and overall plasma thiol status were unaffected. Likewise, a half cup per day had no effect on any biomarkers.
Conclusions
Despite insulin resistance remaining unchanged we show, to our knowledge, the first sustained improvements in vascular function, lipid status, and underlying NO bioactivity following 1 cup blueberries/d. With effect sizes predictive of 12–15% reductions in CVD risk, blueberries should be included in dietary strategies to reduce individual and population CVD risk. This study was registered at clinicaltrials.gov as NCT02035592.
Aim: To determine if the black tea is more effective in serum lipid profile that placebo in subjects with
hypercholesterolemia.
Design: Systematic review with meta-analysis of randomized clinical trials (RCTs).
Data sources: The databases Medline, Central, Embase, Lilacs, Cinahl, SPORTDiscus, and Web of Science
were searched from inception up to January 2019.
Eligibility criteria for selecting studies: RCTs that compared black tea versus placebo, that included serum
lipid profile outcomes in subjects older than 18 years of age with hypercholesterolemia.
Results: Seven RCTs met the eligibility criteria, and for the quantitative synthesis, six studies were
included. Mean difference for total cholesterol was 1.67 mg/dl 95% CI 1⁄4 5.47 to 8.80 (p 1⁄4 0.65), mean
difference 0.28 mg/dl, 95% CI 1⁄4 3.89 to 4.45 (p 1⁄4 0.90) for triglycerides, mean difference 3.21 mg/dl, 95%
CI 1⁄4 11.02 to 4.60 (p 1⁄4 0.42) for low density lipoprotein-cholesterol, mean difference 0.38 mg/dl, 95%
CI 1⁄4 1.12 to 1.87 (p 1⁄4 0.62) for high density lipoprotein-cholesterol.
Conclusion: In the short term, no significant differences were found in lipid serum profile comparing
black tea consumption with placebo.
Background and Aims
Ulcerative colitis (UC) is associated with an increased intestinal permeability, possibly through a dysbiosis of intestinal bacteria. We investigated which markers are most relevant to assess intestinal permeability in UC patients and whether probiotics had an effect on these markers.
Methods
In this twelve-week placebo-controlled randomized double-blind study, twenty-five subjects with UC in remission received either placebo or a multispecies probiotics. Samples of blood, urine, and faeces were taken at baseline, week 6, and week 12 to assess intestinal permeability and inflammation. Diaries and Bristol stool scale were kept to record stool frequency and consistency. Quality of life was scored from 32–224 with the inflammatory bowel disease questionnaire (IBD-Q).
Results
This group of UC patients, in clinical remission, did not show increased intestinal permeability at baseline of this study. During the study, no significant group or time effects were found for intestinal permeability measured by the 5-sugar absorption test, serum zonulin, and faecal zonulin. Likewise, the inflammatory markers C-reactive protein (CRP), calprotectin, and the cytokines IFNγ, TNFα, IL-6, and IL-10 were not significantly affected. Stool frequency and consistency were not significantly affected either. The IBD-Q score, 194 for the probiotics group and 195 for the placebo group, remained unaffected. Correlations were tested between all outcomes; urinary sucrose excretion was significantly correlated with serum zonulin (r = 0.62) and faecal calprotectin (r = 0.55). Faecal zonulin was not significantly correlated with any of the other markers.
Conclusion
Serum zonulin may be a more relevant biomarker of intestinal permeability than faecal zonulin, due to its correlation with other biomarkers of intestinal permeability. UC patients in remission did not show an effect of the probiotic treatment or a change in gut permeability. This should not discourage further studies because effects might be present during active disease or shortly after a flare up.
Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut dysbiosis can critically contribute to the development of rheumatic diseases, including rheumatoid arthritis (RA). Of interest, an adherence to a Mediterranean diet has been linked to a reduction in mortality and morbidity in patients with inflammatory diseases. Diet and intestinal microbiota are modifying factors that may influence intestinal barrier strength, functional integrity, and permeability regulation. Intestinal microbiota may play a crucial role in RA pathogenesis, but up to now no solid data has clarified a mechanistic relationship between gut microbiota and the development of RA. Nonetheless, microbiota composition in subjects with RA differs from that of controls and this altered microbiome can be partially restored after prescribing disease modifying antirheumatic drugs. High levels of Prevotella copri and similar species are correlated with low levels of microbiota previously associated with immune regulating properties. In addition, some nutrients can alter intestinal permeability and thereby influence the immune response without a known impact on the microbiota. However, critical questions remain to be elucidated, such as the way microbiome fluctuates in relation to diet, and how disease activity may be influenced by changes in diet, microbiota or diet-intestinal microbiota equilibrium.
This narrative mini- review summarizes current knowledge of the role of polyphenols in health outcomes—and non-communicable diseases specifically—and discusses the implications of this evidence for public health, and for future directions for public health practice, policy, and research. The publications cited originate mainly from animal models and feeding experiments, as well as human cohort and case-control studies. Hypothesized protective effects of polyphenols in acute and chronic diseases, including obesity, neurodegenerative diseases, type 2 diabetes, and cardiovascular diseases, are evaluated. Potential harmful effects of some polyphenols are also considered, counterbalanced with the limited evidence of harm in the research literature. Recent international governmental regulations are discussed, as the safety and health claims of only a few specific polyphenolic compounds have been officially sanctioned. The implications of food processing on the bioavailability of polyphenols are also assessed, in addition to the health claims and marketing of polyphenols as a functional food. Finally, this mini-review asserts the need for increased regulation and guidelines for polyphenol consumption and supplementation in order to ensure consumers remain safe and informed about polyphenols.
PurposeIncreased gut permeability causes the trespass of antigens into the blood stream which leads to inflammation. Gut permeability reflected by serum zonulin and diversity of the gut microbiome were investigated in this cross-sectional study involving female study participants with different activity and BMI levels. Methods102 women were included (BMI range 13.24–46.89 kg m−2): Anorexia nervosa patients (n = 17), athletes (n = 20), normal weight (n = 25), overweight (n = 21) and obese women (n = 19). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis (V1–V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Zonulin was measured with ELISA. Nutrient intake was assessed by repeated 24-h dietary recalls. We used the median of serum zonulin concentration to divide our participants into a “high-zonulin” (> 53.64 ng/ml) and “low-zonulin” (< 53.64 ng/ml) group. ResultsThe alpha-diversity (Shannon Index, Simpson Index, equitability) and beta-diversity (unweighted and weighted UniFrac distances) of the gut microbiome were not significantly different between the groups. Zonulin concentrations correlated significantly with total calorie-, protein-, carbohydrate-, sodium- and vitamin B12 intake. Linear discriminant analysis effect size (LEfSe) identified Ruminococcaceae (LDA = 4.163, p = 0.003) and Faecalibacterium (LDA = 4.151, p = 0.0002) as significantly more abundant in the low zonulin group. Conclusion
Butyrate-producing gut bacteria such as Faecalibacteria could decrease gut permeability and lower inflammation. The diversity of the gut microbiota in women does not seem to be correlated with the serum zonulin concentration. Further interventional studies are needed to investigate gut mucosal permeability and the gut microbiome in the context of dietary factors.
Hypertension and dyslipidemia are major risk factors for cardiovascular disease (CVD). Common treatments for high blood pressure (BP) and dyslipidemia include medications, but there is question as to whether natural sources may be adequate to reduce CVD risk factors. We examined the effects of tart cherry juice on lipid profiles, BP, glucose, insulin, and homeostatic model assessment-insulin resistance (HOMA-IR) in older adults. In this randomized-controlled clinical trial, 17 men and 20 women between the ages of 65–80 years were randomly assigned to consume 480 ml of tart cherry juice or control drink daily for 12 weeks. Control beverages were matched for energy and sugar content. Outcome variables were assessed at baseline and after 12 weeks of tart cherry juice or control drink. Systolic BP and low-density lipoprotein cholesterol (LDL) exhibited treatment × time interaction effects. At the end of the study, participants in the tart cherry group had lower levels of LDL cholesterol (difference of −20.6 with P = 0.001) and total cholesterol (difference of −19.11 with P = 0.01), and higher levels of glucose (difference of 7.94 with P = 0.001), triglycerides (difference of 6.66 with P = 0.01) and BMI (difference of 1.06 with P = 0.02) than in the control group. Neither tart cherry juice nor control significantly altered body weight, high-density lipoprotein cholesterol, diastolic BP, insulin and HOMA-IR. Our findings show that tart cherry juice can lower the levels of systolic BP and LDL cholesterol. However, larger and longer follow-up studies are needed to further assess cardio-protective effects of tart cherry juice.
Background:
Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.
Methods:
Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).
Results:
Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.
Conclusions:
Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.
Systolic hypertension, especially isolated hypertension (ISH) is very common in older subjects aged ≥ 65 years and is a major risk factor for cardiovascular disease (CVD), strokes, heart failure (HF) and chronic kidney disease (CKD). It is also, directly and linearly related with these complications irrespective of sex, or ethnicity, but it is worse with the advancement of age. Effective control of systolic blood pressure (SBP), is associated with significant reduction in the incidence of these complications. Currently, there is a debate about the optimal SBP control in view of the Systolic Blood Pressure Intervention Trial (SPRINT) showing beneficial cardiovascular (CV) effects of intensive SBP of < 120 mmHg in older patients. Also, the recently released blood pressure (BP) guidelines by the American College of Cardiology, the American Heart Association and the American Society of Hypertension (ACC/AHA/ASH) recommend a SBP reduction of < 130 mmHg. These SBP treatment recommendations are in contrast with the current (JNC VIII) committee of BP treatment guidelines, which recommend a SBP reduction < 150 mmHg for the same age of patients. All these different recommendations have created a debate regarding the optimal treatment targets for the systolic hypertension of the elderly patients. To gain more information a focused Medline search was conducted from 2010 to 2017 using the terms, systolic blood pressure, aggressive control, older subjects, treatment guidelines, and 37 pertinent papers were retrieved. The findings from these studies suggest a SBP reduction of < 140 mm Hg for persons aged ≥ 60 years, with an attempt for SBP reduction to ≤ 130 mm Hg in healthier subjects and hose with CVD, DM, and CKD. Care should be taken not to further reduce the SBP in older subjects if their DBP is ≤ 60 mmHg for the fear of J-curve effect.
Studies on the effects of consuming 100 % fruit juice on measures of glycaemic control are conflicting. The purpose of the present study was to systematically review and quantitatively summarise results from randomised controlled trials (RCT) examining effects of 100 % fruit juice on glucose–insulin homeostasis. Eligible studies were identified from a systematic review of PubMed and EMBASE and hand searches of reference lists from reviews and relevant papers. Using data from eighteen RCT, meta-analyses evaluated the mean difference in fasting blood glucose (sixteen studies), fasting blood insulin (eleven studies), the homeostatic model assessment of insulin resistance (HOMA-IR; seven studies) and glycosylated Hb (HbA1c; three studies) between the 100 % fruit juice intervention and control groups using a random-effects model. Compared with the control group, 100 % fruit juice had no significant effect on fasting blood glucose (−0·13 (95 % CI −0·28, 0·01) mmol/l; P = 0·07), fasting blood insulin (−0·24 (95 % CI −3·54, 3·05) pmol/l; P = 0·89), HOMA-IR (−0·22 (95 % CI −0·50, 0·06); P = 0·13) or HbA1c (−0·001 (95 % CI −0·38, 0·38) %; P = 0·28). Results from stratified analyses and univariate meta-regressions also largely showed no significant associations between 100 % fruit juice and the measures of glucose control. Overall, findings from this meta-analysis of RCT suggest a neutral effect of 100 % fruit juice on glycaemic control. These findings are consistent with findings from some observational studies suggesting that consumption of 100 % fruit juice is not associated with increased risk of diabetes.
The development of human gut microbiota begins as soon as the neonate leaves the protective environment of the uterus (or maybe in-utero) and is exposed to innumerable microorganisms from the mother as well as the surrounding environment. Concurrently, the host responses to these microbes during early life manifest during the development of an otherwise hitherto immature immune system. The human gut microbiome, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, keeps on fluctuating during different stages of life. While these deviations are largely natural, inevitable and benign, recent studies show that unsolicited perturbations in gut microbiota configuration could have strong impact on several features of host health and disease. Our microbiota undergoes the most prominent deviations during infancy and old age and, interestingly, our immune health is also in its weakest and most unstable state during these two critical stages of life, indicating that our microbiota and health develop and age hand-in-hand. However, the mechanisms underlying these interactions are only now beginning to be revealed. The present review summarizes the evidences related to the age-associated changes in intestinal microbiota and vice-versa, mechanisms involved in this bi-directional relationship, and the prospective for development of microbiota-based interventions such as probiotics for healthy aging.
Background
The potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. In this paper, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the precise effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans.
Methods
Comprehensive electronic searches were conducted in PubMed, Embase, and the Cochrane Library. Studies included were RCTs that evaluated the changes in diabetes biomarkers among adults (≥18 years) following pomegranate interventions. The predefined outcomes included fasting blood glucose (FBG), fasting blood insulin (FBI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR). Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using a random-effects model. Publication bias, subgroup analyses, sensitivity analysis and random-effects meta-regression were also performed to explore the influence of covariates on the net changes in fasting glucose and insulin concentrations.
Results
Sixteen eligible trials with 538 subjects were included. The pooled estimates suggested that pomegranate did not significantly affect the measures of FBG (WMD, −0.6 mg/dL; 95% CI, −2.79 to 1.58; P=0.59), FBI (WMD, 0.29 μIU/mL; 95% CI, −1.16 to 1.75; P=0.70), HOMA-IR (WMD, −0.04; 95% CI, −0.53 to 0.46; P=0.88) or HbA1c (WMD, −0.11%; 95% CI, −0.39 to −0.18; P=0.46). Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found in the current meta-analysis.
Conclusion
Pomegranate intake did not show a notably favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results.
Electronic supplementary material
The online version of this article (10.1186/s12937-017-0290-1) contains supplementary material, which is available to authorized users.
Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue. Plasma high-molecular weight adiponectin (HMW adiponectin) was significantly increased after VLCD. Plasma levels of high-sensitivity C-reactive protein (hsCRP) and lipopolysaccharide-binding protein (LBP) were significantly decreased after 28 days of VLCD. Using three different methods, gut paracellular permeability was decreased after VLCD. These changes in clinical parameters were not associated with major consistent changes in dominant bacterial communities in feces. In summary, a 4-week caloric restriction resulted in significant weight loss, improved gut barrier integrity and reduced systemic inflammation in obese women.
Introduction
Increased gut permeability (“leaky gut”) has been proposed as a potential contributor to age-related inflammation and gut dysbiosis. However, information on the relationship between a leaky gut and inflammation and physical frailty during aging are limited.
Objective
To investigate the hypothesis that an aging-associated leaky gut is linked to the age-related inflammation and frailty.
Methods
Two cohorts of healthy adults were studied: young (18–30 years old, n = 19) and older (≥70 years old, n = 18). Serum concentrations of the tumor necrosis factor (TNF)-α and interleukin (IL)-6, zonulin (a marker for leaky gut), and high-mobility group box protein (HMGB1, a nuclear protein triggering inflammation) were measured. Correlations of serum levels of zonulin and HMGB1 with strength of plantar flexor muscles and number of steps taken per day were analyzed.
Results
Serum concentration of zonulin and HMGB1 were 22% (P = .005) and 16% (P = .010) higher in the older versus young adults. Serum zonulin was positively associated with concentrations of TNF-α (r = 0.357, P = .032) and IL-6 (r = 0.345, P = .043). Importantly, both zonulin and HMGB1 were negatively correlated with skeletal muscle strength (zonulin: r = −0.332, P = .048; HMGB1: r = −0.383, P = .023), and habitual physical activity (zonulin: r = −0.410, P = .016; HMGB1: r = −0.483, P = .004).
Conclusions
Serum zonulin was associated with both systemic inflammation and 2 key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty.
Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.
Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects ( n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 ( sem 0·5)×10 ⁻³v . −0·5 ( sem 0·5)×10 ⁻³ mg/kg per min per pmol, respectively, P =0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT ( P =0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.
Background
Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS.
Methods
Ileal biopsies were obtained from 50 HLA-B27⁺ patients with AS and 20 normal subjects. Silver stain was used to visualise bacteria. Ileal expression of tight and adherens junction proteins was investigated by TaqMan real-time (RT)-PCR and immunohistochemistry. Serum levels of lipopolysaccharide (LPS), LPS-binding protein (LPS-BP), intestinal fatty acid-BP (iFABP) and zonulin were assayed by ELISA. Monocyte immunological functions were studied in in vitro experiments. In addition the effects of antibiotics on tight junctions in human leukocyte antigen (HLA)-B27 transgenic (TG) rats were assessed.
Results
Adherent and invasive bacteria were observed in the gut of patients with AS with the bacterial scores significantly correlated with gut inflammation. Impairment of the gut vascular barrier (GVB) was also present in AS, accompanied by significant upregulation of zonulin, and associated with high serum levels of LPS, LPS-BP, iFABP and zonulin. In in vitro studies zonulin altered endothelial tight junctions while its epithelial release was modulated by isolated AS ileal bacteria. AS circulating monocytes displayed an anergic phenotype partially restored by ex vivo stimulation with LPS+sCD14 and their stimulation with recombinant zonulin induced a clear M2 phenotype. Antibiotics restored tight junction function in HLA-B27 TG rats.
Conclusions
Bacterial ileitis, increased zonulin expression and damaged intestinal mucosal barrier and GVB, characterises the gut of patients with AS and are associated with increased blood levels of zonulin, and bacterial products. Bacterial products and zonulin influence monocyte behaviour.
Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage.