Abstract The intestine is the largest interface between the internal body and the external environment. The intestinal barrier is a dynamic system influenced by the composition of the intestinal microbiome and the activity of intercellular connections, regulated by hormones, dietary components, inflammatory mediators, and the enteric nervous system (ENS). Over the years, it has become increasingly evident that maintaining a stable intestinal barrier is crucial to prevent various potentially harmful substances and pathogens from entering the internal environment. Disruption of the barrier is referred to as 'leaky gut' or leaky gut wall syndrome and seems to be characterized by the release of bacterial metabolites and endotoxins, such as lipopolysaccharide (LPS), into the circulation. This condition, mainly caused by bacterial infections, oxidative stress, high-fat diet, exposure to alcohol or chronic allergens, and dysbiosis, appear to be highly connected with the development and/or progression of several metabolic and autoimmune systemic diseases, including obesity, non-alcoholic fatty liver disease (NAFLD), neurodegeneration, cardiovascular disease, inflammatory bowel disease, and type 1 diabetes mellitus (T1D). In this review, starting from a description of the mechanisms that enable barrier homeostasis and analyzing the relationship between this complex ecosystem and various pathological conditions, we explore the role of the gut barrier in driving systemic inflammation, also shedding light on current and future therapeutic interventions. 

Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review.

Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain and altered bowel habit. The origin seems to be multifactorial and is still not well defined for the different subtypes. Genetic, epigenetic and sex-related modifications of the functioning of the nervous and immune-endocrine supersystems and regulation of brain-gut physiology and bile acid production and absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary and life event-related factors to enhance epithelial permeability and elicit mucosal microinflammation, immune activation and dysbiosis. Notably, strong evidence supports the role of bacterial, viral and parasitic infections in triggering IBS, and targeting microbiota seems promising in view of the positive response to microbiota-related therapies in some patients. However, the lack of highly predictive diagnostic biomarkers and the complexity and heterogeneity of IBS patients make management difficult and unsatisfactory in many cases, reducing patient health-related quality of life and increasing the sanitary burden. This article reviews specific alterations and interventions targeting the gut microbiota in IBS, including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation and other potential future approaches useful for the diagnosis, prevention and treatment of IBS.

/pdf/a-review-of-microbiota-and-irritable-bowel-syndrome-future-v5oe8ywe2m.pdf

A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies

Diabetes mellitus (DM) and its complications are major public health concerns which strongly influence the quality of humans' life. Modification of gut microbiota has been widely used for the management of diabetes. In this review, the relationship between diabetes and gut microbiota, as well as the effects of different dietary components and traditional Chinese medicine (TCM) on gut microflora are summarized. Dietary compounds and TCM possessing bioactive components (fiber and phytochemicals) first change the composition of gut microbiota (inhibiting pathogens and promoting the beneficial bacteria growth) and then influence the production of their metabolites, which would further modify the intestinal environment through inhibiting the production of detrimental compounds (such as lipopolysaccharide, hydrogen sulfide, indol, etc.). Importantly, metabolites (short chain fatty acids and other bioactive components) fermented/degraded by gut microbiota can target multiple pathways in intestine, liver, pancreas, etc., resulting in the improvement of gut health, glycemic control, lipids profile, insulin resistance and inflammation. Furthermore, understanding the interaction between different dietary components and gut microbiota, as well as underlying mechanisms would help design different diet formula for the management of diabetes. Further researches could focus on the combination of different dietary components for preventing and treating diabetes, based on the principle of "multiple components against multiple targets" from the perspective of gut microbiota.

Dietary compounds and traditional Chinese medicine ameliorate type 2 diabetes by modulating gut microbiota.

Treatment strategies against diabetes: Success so far and challenges ahead.

The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut microbiota and glucose control and lipid levels in individuals with diabetes. MEDLINE, EMBASE and the Cochrane Library were searched. The eligibility criteria for the studies was involvement of participants with a diagnosis of type 1 or type 2 diabetes. Metabolic outcomes (glucose control, insulinaemia, and lipid profile) of any probiotic, prebiotic or synbiotic supplementation related to modification of gut microbiota (prebiotics, probiotics and synbiotics) were analysed. We provided a narrative synthesis and meta-analysis of the findings on metabolic outcomes from the studies. Metabolic outcomes were extracted post-intervention and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. We pooled the results using a random-effects meta-analysis. The meta-analysis was conducted using Review Manager (RevMan) software. After the removal of duplicates and ineligible studies, 5219 studies were retained for review of titles and abstracts. The number of articles was reduced to 130 by review, for which the full-text articles were obtained and reassessed, 38 of which were included in the final meta-analysis. Overall, the use of prebiotics, probiotics or synbiotics reduced HbA1c levels, but did not reach the threshold for significance (−2.17 mmol/mol, 95% CI −4.37, 0.03; p = 0.05, [−0.20%, 95% CI −0.40 to 0.00; p = 0.05, I2 = 66%]) and had no effect on LDL-cholesterol levels (−0.05 mmol/l; 95% CI −0.14, 0.05, p = 0.35, I2 = 37%). However, their consumption decreased levels of fasting blood glucose (−0.58 mmol/l; 95% CI −0.86, −0.30; p < 0.01, I2 = 60%), total cholesterol (−0.14 mmol/l; 95% CI −0.26, −0.02, p = 0.02, I2 = 39%), triacylglycerols (−0.11 mmol/l; 95% CI −0.20, −0.02, p = 0.01, I2= 21%) and insulinaemia (−10.51 pmol/l; 95% CI −16.68,−4.33, p < 0.01, I2 = 74%), and increased HDL-cholesterol levels (0.04 mmol/l; 95% CI 0.01, 0.07, p < 0.01, I2= 24%). In individuals with diabetes mellitus, supplementation with probiotics, prebiotics or synbiotics improved metabolic variables, although the magnitude of this effect is low. Our results suggest that consumption of probiotics, prebiotics or synbiotics may be a potential adjuvant treatment for improving metabolic outcomes. PROSPERO ID CRD42017080071.

/pdf/the-effect-of-probiotics-prebiotics-or-synbiotics-on-110zudechp.pdf

The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis

Gut microbiota affects the host’s metabolism, and it is suggested that there are differences in gut microbiota composition between patients with type 2 diabetes and healthy individuals. Additionally, dysbiosis may increase the concentration of lipopolysaccharides (LPS), causing metabolic endotoxemia, which induces impaired glucose tolerance. Several studies have reported relationships between metabolic diseases and the gut microbiota; and prebiotics, such as oligosaccharides, are commonly consumed to regulate gut microbiotas in healthy individuals. Galacto-oligosaccharides (GOS) are a major prebiotic, which specifically increase Bifidobacteriaceae abundance. Recent studies have reported that Bifidobacteriaceae improved metabolic endotoxemia or impaired glucose tolerance. However, there are few studies reporting the effects of GOS on patients with type 2 diabetes. In the current study, we compared clinical parameters, faecal gut microbiota, their associated metabolic products and their components such as L...

Galacto-oligosaccharides ameliorate dysbiotic Bifidobacteriaceae decline in Japanese patients with type 2 diabetes.

Chronic inflammation caused by gut dysbiosis is associated with the pathophysiology of metabolic disease. Synbiotics are useful for ameliorating gut dysbiosis; however, it remains unclear what types of bacteria act as key markers for synbiotic-driven improvement of chronic inflammation. Here, we performed a post hoc analysis of a 24-week randomized controlled study using synbiotics to investigate the association between gut microbiota and inflammatory markers. We characterized the responders who showed lower interleukin-6 (IL-6) levels in response to synbiotic supplementation among 86 obese patients with type 2 diabetes mellitus. In our baseline analysis, the relative abundances of Bifidobacterium adolescentis and Alistipes onderdonkii correlated positively with IL-6, lipopolysaccharide binding protein (LBP), and high-sensitivity C-reactive protein (Hs-CRP) levels. The relative abundance of Eubacterium rectale correlated positively with LBP and Hs-CRP levels, and that of Bacteroides thetaiotaomicron correlated positively with LBP levels. Based on our responder analysis, patients with higher body mass indices (over 30 kg/m2 on average), low abundances of Bacteroides caccae and Parabacteroides merdae at baseline and 24 weeks, and minimal changes in the relative abundance of E. rectale and Shannon index from baseline showed decreased IL-6 levels compared with baseline. However, glycemic control in responders was unchanged. In conclusion, we identified four bacterial species (B. adolescentis, A. onderdonkii, E. rectale, and B. thetaiotaomicron) related to chronic inflammation and predictive markers (B. caccae, P. merdae, and severity of obesity) in responders to synbiotic supplementation among obese patients with type 2 diabetes.

Association of gut microbiota and inflammatory markers in obese patients with type 2 diabetes mellitus: post hoc analysis of a synbiotic interventional study

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Galacto-oligosaccharides ameliorate dysbiotic Bifidobacteriaceae decline in Japanese patients with type 2 diabetes.

Association of gut microbiota and inflammatory markers in obese patients with type 2 diabetes mellitus: post hoc analysis of a synbiotic interventional study