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Bidirectional crosstalk along the gut-liver axis controls gastrointestinal health and disease and exploits environmental and host mediators. Nutrients, microbial antigens, metabolites, and bile acids regulate metabolism and immune responses in the gut and liver, which reciprocally shape microbial community structure and function. Perturbation of such host-microbe interactions is observed in a variety of experimental liver diseases and is facilitated by an impaired intestinal barrier, which is fueling hepatic inflammation and disease progression. Clinical evidence describes perturbation of the gut-liver crosstalk in non-alcoholic fatty liver disease, alcoholic liver disease, and primary sclerosing cholangitis. In liver cirrhosis, a common sequela of these diseases, the intestinal microbiota and microbial pathogen-associated molecular patterns constitute liver inflammation and clinical complications, such as hepatic encephalopathy. Understanding the intricate metabolic interplay between the gut and liver in health and disease opens an avenue for targeted therapies in the future, which is probed in controlled clinical trials. Tilg et al. discuss experimental and clinical aspects of the bidirectional gut-liver crosstalk in health and how perturbation of such inter-organ communication promotes liver diseases. Collectively, the diet, gut mucosal immunity and related microbial commensalism, and hepatic metabolism shape the communication along the gut-liver axis, fueling various liver diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased intestinal permeability, known as leaky gut syndrome, occurs when the intestinal lining of the gastrointestinal tract has been damaged. The influx of unwanted material in the bloodstream can induce an immune response releasing proinflammatory cytokines that have been thought to be correlated with dermatologic conditions. OBJECTIVE: We aimed to evaluate the role of leaky gut in dermatological conditions. Methods: PubMed and Embase were systematically searched through September 2020 for clinical studies that measured intestinal permeability in participants with a dermatological condition. RESULTS: We identified 20 studies including participants with dermatitis herpetiformis, atopic dermatitis/eczema, systemic sclerosis, psoriasis, bullous pemphigoid, and pemphigus vulgaris/foliaceus. Atopic dermatitis was the most well studied. Studies utilized a range of measures of intestinal permeability, including sugar excretion tests and serum markers. For all disorders reviewed, except bullous pemphigoid and pemphigus vulgaris/foliaceus, there was evidence of increased intestinal permeability in the disease state compared with controls. LIMITATIONS: The range of methodology across clinical studies makes it difficult to draw conclusions across results. In addition, studies tended to be small, and only one study included an intervention to target leaky gut syndrome. CONCLUSIONS: We have found preliminary evidence of a relationship between leaky gut and certain dermatological conditions. [ABSTRACT FROM AUTHOR]

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. 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. 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 × time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment × 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 fibre-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. 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 fibre-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. ISRCTN10214981. The effect of an 8-week, randomized, controlled, dietary intervention consisting of a polyphenol-rich diet (PR-diet) versus control diet (C-diet) was evaluated in older subjects with increased intestinal permeability. A plethora of markers related to intestinal permeability, anthropometrics, host function and metabolism, oxidative stress, vascular and inflammatory response, microbiota composition and dietary intake have been analysed. The PR-diet intervention significantly increased polyphenol intake, reduced serum zonulin levels (primary outcome of intestinal permeability) and diastolic blood pressure while increased fibre fermenting and butyrate-producing bacteria. [Display omitted] [ABSTRACT FROM AUTHOR]

Intestinal barrier dysfunction and dysbiosis contribute to development of diseases in liver and other organs. Physical, immunologic, and microbiologic (bacterial, fungal, archaeal, viral, and protozoal) features of the intestine separate its nearly 100 trillion microbes from the rest of the human body. Failure of any aspect of this barrier can result in translocation of microbes into the blood and sustained inflammatory response that promote liver injury, fibrosis, cirrhosis, and oncogenic transformation. Alterations in intestinal microbial populations or their functions can also affect health. We review the mechanisms that regulate intestinal permeability and how changes in the intestinal microbiome contribute to development of acute and chronic liver diseases. We discuss individual components of the intestinal barrier and how these are disrupted during development of different liver diseases. Learning more about these processes will increase our understanding of the interactions among the liver, intestine, and its flora. [ABSTRACT FROM AUTHOR]

The most frequent cause of gastrointestinal disorders characterized by inflammation and disturbance of the gastrointestinal system, is infection from various bacterial strains. Garcinia morella (Gaertn.) Desr. (Clusiaceae) a well-known traditional food is also used in healing digestive disorders for centuries. However, its protective activity in the pathogenesis of pathogen-induced gut disruption remains unclear. This study investigated the beneficial effect of G. morella fruits in remediating pathogen-induced intestinal disruption in Caco-2 cells. The antimicrobial activity of G. morella hydroalcoholic fruit extract with known chemical composition against the opportunistic pathogens, Escherichia coli and Enterococcus faecalis were evaluated. Transepithelial electrical resistance and dextran permeability assay were performed to evaluate the permeability in Caco-2 monolayers. Western blot assays were performed to detect the expression of the intestinal tight junction proteins: zonula occludens-1, claudin-1, occludin, and E-cadherin; and phosphorylation of inflammatory markers: ERK (Extracellular signal-regulated kinase), and JNK (Jun N-terminal kinase). Three bioactive compounds: garcinol, hydroxycitric acid, and hydroxycitric acid lactone were identified, qualitatively and quantitatively assessed with HPLC (high performance liquid chromatography). G. morella hydroalcoholic extract and its compounds prevented the decrease in transepithelial electrical resistance caused by pathogen infection in Caco-2 cells. G. morella and compounds also decreased permeability in Caco-2 monolayer, increased by pathogen infection. G. morella and garcinol enhanced tight junction protein expression. A decrease in extracellular-signal-regulated kinase and c-Jun N-terminal kinase phosphorylation was observed in G. morella and garcinol-treated cells. Overall, the results showed the potential of G. morella and its compounds in maintaining intestinal integrity and validate its traditional claims in ameliorating stomach ailments. The study also provided new guidance in development of nutraceuticals that aid in curing leaky gut. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that obesity can increase intestinal permeability (i.e., leaky gut). Intestinal permeability is the unmediated transport of large, normally restricted substances across the GI epithelium. Increased intestinal permeability can result in local and/or systemic inflammatory conditions. The purpose of this study was to determine the effect of percent body fat on small intestinal permeability. Ten healthy female and three healthy male subjects (mean age = 23 ± 6 yrs) had their percent body fat determined with Bod Pod, an air displacement plethysmograph unit. Then, the subjects ingested a 150 mL solution containing 5 g lactulose and 2 g mannitol followed by the collection of their urine for a 5-hr period. The urine was analyzed for lactulose and mannitol concentration. Percent urinary excretion of the ingested lactulose and mannitol was determined by multiplying the urinary concentrations of each sugar by the total urine produced and dividing the result by the amount ingested. The lactulose to mannitol excretion ratio (L/M) is an index of small intestinal permeability. The correlation (r = -0.223) between percent body fat and the L/M ratio was not significant. This result indicates that small intestinal permeability may not be associated with percent body fat in younger healthy individuals. [ABSTRACT FROM AUTHOR]

Intestinal permeability is the property that allows solute and fluid exchange between intestinal lumen and intestinal mucosa. Many factors could have major impact on its regulation, including gut microbiota, mucus layer, epithelial cell integrity, epithelial junction, immune responses, intestinal vasculature, and intestinal motility. Any change among these factors could have an impact on intestinal homeostasis and gut permeability. Healthy condition is associated to normal intestinal permeability whereas several intestinal and extra intestinal disease, like inflammatory bowel disease, irritable bowel syndrome, non-alcoholic fatty liver disease among others, are associated to increased intestinal permeability. This review aims to synthesize determinants on intestinal permeability and to report methodologies useful to the measurement of intestinal permeability in clinical practice as well as in research settings. [ABSTRACT FROM AUTHOR]

Background This study aims to explore the conditions complementary and integrative medicine (CIM) practitioners associate with increased intestinal permeability (IP) and the methods they employ to assess IP. Methods A cross-sectional survey of naturopaths, nutritionists and Western herbal medicine practitioners was undertaken (n = 227) through the Practitioner Research and Collaboration Initiative (PRACI) network. Results CIM practitioners (n = 36, response rate 15.9%) associate IP with gastrointestinal (100.0%), autoimmune (91.7%), skin (91.7%), neurological (80.6%), respiratory (55.6%) and liver-related conditions (44.4%). CIM practitioners frequently treat IP (72.7%); observing a minimum 3 months of treatment is required to resolve IP. Patient's signs and symptoms were the main reasons CIM practitioners suspected IP (94.1%). Conclusion CIM practitioners observe a clinical link between IP and a wide range of conditions, including those not yet recognised within the literature. The clinical experience of CIM practitioners holds substantial value to the advancement of research and the clinical management of IP. [ABSTRACT FROM AUTHOR]

Introduction Two of the three pillars of evidence-based practice emphasise the importance of using the best available academic research and experience from clinical practice to inform patient care. This paper aims to outline the potential value of exploring and describing insights from clinical practice through health services research to inform whole system research. Methods Concepts and ideas were developed from non-systematic review of published literature and extensive academic and clinical experience within the disciplines of health services research and clinical trials. Results Through deductive reasoning, complementary and integrative medicine (CIM) practitioners may have identified new understanding of the management of disease not yet seen in published literature. The area where investigating CIM practitioners in clinical practice may advance the clinical understanding of particular conditions is extensive. For instance, increased intestinal permeability (IP) is speculated to be involved in diseases frequently seen within clinical practice. IP is considered multifactorial with involvement from genetic and environmental factors. Conclusions CIM practitioners report clinical experience in the management of digestive disorders; their practice wisdom may add new knowledge to the significance of IP within clinical practice and outline testing parameters. Furthermore, the whole system treatment approach used by CIM practitioners may provide insight into new options for the management of IP not known or shared in published literature. Investigating the approaches CIM practitioners use within clinical practice may provide advancements in the clinical understanding of IP and other conditions. Exploring clinical practice may identify new knowledge that may translate to improvement in patient care. [ABSTRACT FROM AUTHOR]

All species, including horses, suffer from alterations that increase intestinal permeability. These alterations, also known as “leaky gut,” may lead to severe disease as the normal intestinal barrier becomes compromised and can no longer protect against harmful luminal contents including microbial toxins and pathogens. Leaky gut results from a variety of conditions including physical stressors, decreased blood flow to the intestine, inflammatory disease, and pathogenic infections, among others. Several testing methods exist to diagnose these alterations in both a clinical and research setting. To date, most research has focused on regulation of the host immune response due to the wide variety of factors that can potentially influence the intestinal barrier. This article serves to review the normal intestinal barrier, measurement of barrier permeability, pathogenesis and main causes of altered permeability, and highlight potential alternative therapies of leaky gut in horses while relating what has been studied in other species. Conditions resulting in barrier dysfunction and leaky gut can be a major cause of decreased performance and also death in horses. A better understanding of the intestinal barrier in disease and ways to optimize the function of this barrier is vital to the long-term health and maintenance of these animals. [ABSTRACT FROM AUTHOR]

[Display omitted] • A diet containing a fermented milk product (FMP) reduces food intake in rats. • FMP diet reduces hepatic triacylglycerol (TG) levels in cholic-acid (CA)-fed rats. • Enhanced in vivo gut permeability induced by CA was inhibited by the FMP diet. • FMP diet enhances the fecal excretion of TG and non-12-hydroxylated bile acids. We investigated whether a diet containing fermented milk products (FMP) improves hepatic lipid accumulation and gut permeability induced by cholic acid (CA) supplementation. After acclimation, male Slc:Wistar rats were fed diets supplemented with a combination of FMP and/or CA (0.5 g/kg diet) for four weeks. FMP was used as a protein source. The FMP-containing diet reduced the total food intake and hepatic triacylglycerol levels without altering the body weight. Enhanced in vivo gut permeability induced by CA was inhibited by the FMP diet. The FMP diet also enhanced the excretion of fecal triacylglycerol and the fecal concentration of non-12-hydroxylated BAs. Multiple regression analysis revealed that total food intake, fecal deoxycholic acid concentration, and fecal triacylglycerol excretion were predictors of hepatic triacylglycerol concentration. A negative correlation was observed between fecal non-12-hydroxylated BAs and hepatic triacylglycerol concentration. These results imply that FMP contributes to reduced hepatic lipid accumulation and normalised gut permeability. [ABSTRACT FROM AUTHOR]

[Display omitted] • The islets of the GDM offspring mice show a "pre-mature" state at birth. • BiLaEn can avoid the excessive development of islets in GDM offspring mice. • The mTORC1 signaling in islets of GDM mice is not synchronized with normal. Gestational diabetes mellitus (GDM) amplifies the intergenerational risk for early-onset metabolic diseases in offspring, yet the pathogenesis remains unclear. We investigated the impacts of GDM on islets development and maturation in offspring mice and whether probiotics (BiLaEn) have protective effects. Strikingly, GDM caused abnormal prenatal development of islets in offspring mice, with abnormally high-expression insulin and glucagon at birth, showing premature or quasi-mature state; the process of β-cell maturation and mTORC1 signalling were not synchronized with normal offspring mice within 14 days after birth. Furthermore, BiLaEn treatment benefited the normal development and maturation of GDM-offspring islets, avoiding "quasi-mature" at birth, which were based on the improvement of intestinal flora disturbance and leaky gut in GDM maternal mice. These data highlight the premature development of GDM-offspring islets as potential cause of early-onset metabolic diseases in GDM offspring, and targeted regulation of intestinal flora is expected to be safe and effective intervention. [ABSTRACT FROM AUTHOR]

Although a link between the gut microbiota and alcohol-related liver diseases (ALDs) has previously been suggested, the causative effects of specific taxa and their functions have not been fully investigated to date. Here, we analyze the gut microbiota of 410 fecal samples from 212 Korean twins by using the Alcohol Use Disorders Identification Test (AUDIT) scales to adjust for host genetics. This analysis revealed a strong association between low AUDIT scores and the abundance of the butyrate-producing genus Roseburia. When Roseburia spp. are administered to ALD murine models, both hepatic steatosis and inflammation significantly improve regardless of bacterial viability. Specifically, the flagellin of R. intestinalis, possibly through Toll-like receptor 5 (TLR5) recognition, recovers gut barrier integrity through upregulation of the tight junction protein Occludin and helps to restore the gut microbiota through elevated expression of IL-22 and REG3γ. Our study demonstrates that Roseburia spp. improve the gut ecosystem and prevent leaky gut, leading to ameliorated ALDs. • The depletion of Roseburia is associated with alcohol consumption in human cohorts • R. intestinalis ameliorates the experimental ALD in mice regardless of viability • Flagellin from R. intestinalis protects on ethanol-disrupted gut barrier functions • The ethanol-induced gut microbiota dysbiosis is restored by R. intestinalis The gut microbiota has been indicated as a critical player in alcoholic liver disease via the gut-liver axis. We identified that Roseburia is strongly negatively associated with high alcohol consumption without significant heritability. The causatively ameliorative effects of Roseburia spp. on experimental ALD were by increasing intestinal tight junctions. [ABSTRACT FROM AUTHOR]

Background & Aims Many patients with inflammatory bowel diseases (IBD) have ongoing bowel symptoms of diarrhea or abdominal pain despite mucosal healing. We investigated whether impaired intestinal permeability contributes to these symptoms. Methods We performed a prospective study of intestinal permeability, measured by endoscopic confocal laser endomicroscopy in 110 consecutive subjects (31 with ulcerative colitis [UC], 57 with Crohn’s disease [CD], and 22 healthy individuals [controls]) in Sydney, Australia from May 2009 and September 2015. Symptomatic CD was defined by a CD Activity Index score of 150 or more and symptomatic UC by a partial Mayo score of 2 or more. Mucosal healing was defined as CD Endoscopic Index of Severity of 0 in CD or Mayo endoscopic sub-score of 0–1 for patients with UC. Intestinal permeability was quantified by the Confocal Leak Score (CLS; range: 0=no impaired permeability to 100=complete loss of barrier function). The primary endpoint was intestinal permeability in patients with symptomatic IBD in mucosal healing vs patients with asymptomatic IBD in mucosal healing. We determined the sensitivity and specificity of CLS in determining symptoms based on receiver operating characteristic analysis. Results Ongoing bowel symptoms were present in 16.3% of patients with IBD and mucosal healing (15.4% of patients with CD, 17.4% with UC). Patients with symptomatic IBD had a significantly higher median CLS (19.0) than patients with asymptomatic IBD (7.3; P < .001) or controls (5.9, P < .001). There were no significant differences between patients with IBD in remission vs controls ( P = .261). Median CLS was significantly higher in patients with symptomatic than asymptomatic CD (17.7 vs 8.1; P = .009) and patients with symptomatic than asymptomatic UC (22.2 vs 6.9; P = .021). A CLS of 13.1 or more identified ongoing bowel symptoms in patients with IBD and mucosal healing with 95.2% sensitivity and 97.6% specificity; the receiver operating characteristic area under curve value was 0.88. Based on this cutoff, 36.2% of patients with IBD in mucosal healing have increased intestinal permeability. On regression analysis, every increase in CLS of 1.9 correlated with an additional diarrheal motion per day ( P = .008). Conclusions In a prospective study of intestinal permeability in patients with IBD and mucosal healing, we associated impaired intestinal permeability with ongoing bowel symptoms; increases in permeability correlated with increased severity of diarrhea. Resolution of mucosal permeability beyond mucosal healing might improve outcomes of patients with IDB (ANZCTR.org.au: ACTRN12613001248752). [ABSTRACT FROM AUTHOR]