Noninvasive Biomarkers of Gut Barrier Function in Patients Suffering from Diarrhea Predominant-IBS: An Update

The intestinal barrier plays a crucial role in the absorption of nutrients and in preventing the entry of pathogenic microorganisms and toxic molecules. Several studies have shown a compromised intestinal barrier associated with low-grade inflammation in the small intestinal mucosa in celiac disease, inflammatory bowel disease, and irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). In light of these new data, IBS is no longer considered a functional disease but rather a heterogeneous syndrome that has yet to be carefully studied. Therefore, investigating the integrity and function of the intestinal barrier is now essential to improving knowledge of the pathophysiology of IBS-D and to improving the management of IBS-D patients. However, the study of the intestinal barrier must clarify some still unsolved methodological aspects and propose standardised assays before becoming a useful diagnostic tool. In this framework, this review will discuss data about the tests that noninvasively evaluate the integrity and functionality of the human intestinal barrier, paying particular attention to patients with IBS-D, in both clinical and research situations.

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Inflammatory Bowel Diseases and Sarcopenia: The Role of Inflammation and Gut Microbiota in the Development of Muscle Failure

Frontiers in Immunology ◽

10.3389/fimmu.2021.694217 ◽

2021 ◽

Vol 12 ◽

Author(s):

Olga Maria Nardone ◽

Roberto de Sire ◽

Valentina Petito ◽

Anna Testa ◽

Guido Villani ◽

...

Keyword(s):

Gut Microbiota ◽

Adverse Outcomes ◽

Low Grade ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Function ◽

Host Metabolism ◽

Low Grade Inflammation

Sarcopenia represents a major health burden in industrialized country by reducing substantially the quality of life. Indeed, it is characterized by a progressive and generalized loss of muscle mass and function, leading to an increased risk of adverse outcomes and hospitalizations. Several factors are involved in the pathogenesis of sarcopenia, such as aging, inflammation, mitochondrial dysfunction, and insulin resistance. Recently, it has been reported that more than one third of inflammatory bowel disease (IBD) patients suffered from sarcopenia. Notably, the role of gut microbiota (GM) in developing muscle failure in IBD patient is a matter of increasing interest. It has been hypothesized that gut dysbiosis, that typically characterizes IBD, might alter the immune response and host metabolism, promoting a low-grade inflammation status able to up-regulate several molecular pathways related to sarcopenia. Therefore, we aim to describe the basis of IBD-related sarcopenia and provide the rationale for new potential therapeutic targets that may regulate the gut-muscle axis in IBD patients.

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Relationship between gut microbiota, gut hyperpermeability, and obesity

Current Medicinal Chemistry ◽

10.2174/0929867327666200721160313 ◽

2020 ◽

Vol 27 ◽

Author(s):

Amin Gasmi ◽

Pavan Kumar Mujawdiya ◽

Lyudmila Pivina ◽

Alexandru Doşa ◽

Yuliya Semenova ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Disorders ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Close Relation ◽

Low Grade ◽

Cytokine Levels ◽

Inflammatory Bowel ◽

Low Grade Inflammation ◽

The Relationship

: Intestinal hyperpermeability is a complex metabolic process mediated by different pathways in close relation to the gut microbiota. Previous studies suggested that the gut microbiota is involved in different metabolic regulations, and its imbalance is associated with several metabolic diseases, including obesity. It is well known that intestinal hyperpermeability is associated with dysbiosis, and the combination of these two conditions can lead to an increase in the level of low-grade inflammation in obese patients due to an increase in pro-inflammatory cytokine levels. Inflammatory bowel syndrome often accompanies this condition causing an alteration of the intestinal mucosa and thus reinforcing the dysbiosis and gut hyperpermeability. The onset of metabolic disorders depends on violations of the integrity of the intestinal barrier as a result of increased intestinal permeability. Chronic inflammation due to endotoxemia is responsible for the development of obesity. Metabolic disorders are associated with dysregulation of the microbiota-gut-brain axis and with an altered composition of gut flora. In this review, we will discuss the mechanisms that illustrate the relationship between hyperpermeability, the composition of the gut microbiota, and obesity.

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Consumption of Select Dietary Emulsifiers Exacerbates the Development of Spontaneous Intestinal Adenoma

International Journal of Molecular Sciences ◽

10.3390/ijms22052602 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2602

Author(s):

Emilie Viennois ◽

Benoit Chassaing

Keyword(s):

Intestinal Inflammation ◽

Tumor Development ◽

Low Grade ◽

Gastrointestinal Cancers ◽

Cancer Initiation ◽

And Function ◽

The Impact ◽

Chronic Intestinal Inflammation ◽

Low Grade Inflammation ◽

Intestinal Adenoma

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APCmin mice, we observed that dietary emulsifiers consumption enhanced small-intestine tumor development in a way that appeared to be independent of chronic intestinal inflammation but rather associated with emulsifiers’ impact on the proliferative status of the intestinal epithelium as well as on intestinal microbiota composition in both male and female mice. Overall, our findings further support the hypothesis that emulsifier consumption may be a new modifiable risk factor for colorectal cancer (CRC) and that alterations in host–microbiota interactions can favor gastrointestinal carcinogenesis in individuals with a genetical predisposition to such disorders.

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New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

World Journal of Gastroenterology ◽

10.3748/wjg.v23.i36.6593 ◽

2017 ◽

Vol 23 (36) ◽

pp. 6593-6627 ◽

Cited By ~ 14

Author(s):

Emanuele Sinagra ◽

Gaetano Cristian Morreale ◽

Ghazaleh Mohammadian ◽

Giorgio Fusco ◽

Valentina Guarnotta ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Low Grade ◽

Neuroendocrine Axis ◽

Irritable Bowel ◽

Low Grade Inflammation

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Evidence from comparative genomic analyses indicating that Lactobacillus-mediated irritable bowel syndrome alleviation is mediated by the conjugated linoleic acid synthesis

Food & Function ◽

10.1039/d0fo02616f ◽

2021 ◽

Author(s):

Yang Liu ◽

Wei Xiao ◽

Leilei Yu ◽

Fengwei Tian ◽

Gang Wang ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Linoleic Acid ◽

Gut Microbiota ◽

Acid Synthesis ◽

Comparative Genomic ◽

Low Grade ◽

Genomic Analyses ◽

Irritable Bowel ◽

Low Grade Inflammation ◽

Gut Microbiota Dysbiosis

Irritable bowel syndrome (IBS) is a chronic intestinal disorder accompanied by low-grade inflammation, visceral hypersensitivity, and gut microbiota dysbiosis. Several studies have indicated that Lactobacillus supplementation can help to alleviate...

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Individualized Responses of Gut Microbiota to Dietary Intervention Modeled in Humanized Mice

mSystems ◽

10.1128/msystems.00098-16 ◽

2016 ◽

Vol 1 (5) ◽

Cited By ~ 24

Author(s):

Samuel A. Smits ◽

Angela Marcobal ◽

Steven Higginbottom ◽

Justin L. Sonnenburg ◽

Purna C. Kashyap

Keyword(s):

Gut Microbiota ◽

Dietary Intervention ◽

Scientific Evidence ◽

Marker Gene ◽

Gastrointestinal Symptoms ◽

Dietary Interventions ◽

Inflammatory Bowel ◽

Irritable Bowel ◽

And Function ◽

Generation Sequencing

ABSTRACT Dietary modification has long been used empirically to modify symptoms in inflammatory bowel disease, irritable bowel syndrome, and a diverse group of diseases with gastrointestinal symptoms. There is both anecdotal and scientific evidence to suggest that individuals respond quite differently to similar dietary changes, and the highly individualized nature of the gut microbiota makes it a prime candidate for these differences. To overcome the typical confounding factors of human dietary interventions, here we employ ex-germfree mice colonized by microbiotas of three different humans to test how different microbiotas respond to a defined change in carbohydrate content of diet by measuring changes in microbiota composition and function using marker gene-based next-generation sequencing and metabolomics. Our findings suggest that the same diet has very different effects on each microbiota’s membership and function, which may in turn explain interindividual differences in response to a dietary ingredient. Diet plays an important role in shaping the structure and function of the gut microbiota. The microbes and microbial products in turn can influence various aspects of host physiology. One promising route to affect host function and restore health is by altering the gut microbiome using dietary intervention. The individuality of the microbiome may pose a significant challenge, so we sought to determine how different microbiotas respond to the same dietary intervention in a controlled setting. We modeled gut microbiotas from three healthy donors in germfree mice and defined compositional and functional alteration following a change in dietary microbiota-accessible carbohydrates (MACs). The three gut communities exhibited responses that differed markedly in magnitude and in the composition of microbiota-derived metabolites. Adjustments in community membership did not correspond to the magnitude of changes in the microbial metabolites, highlighting potential challenges in predicting functional responses from compositional data and the need to assess multiple microbiota parameters following dietary interventions. IMPORTANCE Dietary modification has long been used empirically to modify symptoms in inflammatory bowel disease, irritable bowel syndrome, and a diverse group of diseases with gastrointestinal symptoms. There is both anecdotal and scientific evidence to suggest that individuals respond quite differently to similar dietary changes, and the highly individualized nature of the gut microbiota makes it a prime candidate for these differences. To overcome the typical confounding factors of human dietary interventions, here we employ ex-germfree mice colonized by microbiotas of three different humans to test how different microbiotas respond to a defined change in carbohydrate content of diet by measuring changes in microbiota composition and function using marker gene-based next-generation sequencing and metabolomics. Our findings suggest that the same diet has very different effects on each microbiota’s membership and function, which may in turn explain interindividual differences in response to a dietary ingredient. Author Video: An author video summary of this article is available.

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Irritable bowel syndrome: new insights into symptom mechanisms and advances in treatment

F1000Research ◽

10.12688/f1000research.7992.1 ◽

2016 ◽

Vol 5 ◽

pp. 780 ◽

Cited By ~ 15

Author(s):

Robin Spiller

Keyword(s):

Irritable Bowel Syndrome ◽

New Agents ◽

Enteric Nerves ◽

Inflammatory Bowel ◽

Magnetic Resonance Imaging Mri ◽

Irritable Bowel ◽

Fodmap Diet ◽

And Function ◽

The Impact

Despite being one of the most common conditions leading to gastroenterological referral, irritable bowel syndrome (IBS) is poorly understood. However, recent years have seen major advances. These include new understanding of the role of both inflammation and altered microbiota as well as the impact of dietary intolerances as illuminated by magnetic resonance imaging (MRI), which has thrown new light on IBS. This article will review new data on how excessive bile acid secretion mediates diarrhea and evidence from post infectious IBS which has shown how gut inflammation can alter gut microbiota and function. Studies of patients with inflammatory bowel disease (IBD) have also shown that even when inflammation is in remission, the altered enteric nerves and abnormal microbiota can generate IBS-like symptoms. The efficacy of the low FODMAP diet as a treatment for bloating, flatulence, and abdominal discomfort has been demonstrated by randomized controlled trials. MRI studies, which can quantify intestinal volumes, have provided new insights into how FODMAPs cause symptoms. This article will focus on these areas together with recent trials of new agents, which this author believes will alter clinical practice within the foreseeable future.

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Modulation of the Gut Microbiota by Shen-Yan-Fang-Shuai Formula Improves Obesity Induced by High-Fat Diets

Frontiers in Microbiology ◽

10.3389/fmicb.2020.564376 ◽

2020 ◽

Vol 11 ◽

Author(s):

Zhen Wang ◽

Junfeng Lu ◽

Jingwei Zhou ◽

Weiwei Sun ◽

Yang Qiu ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Disorders ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

16S Rrna Genes ◽

Rrna Genes ◽

Therapeutic Effects ◽

Low Grade ◽

High Fat ◽

Gut Barrier Function

Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Shen-Yan-Fang-Shuai formula (SYFSF) is a traditional Chinese herbal formula composed of Astragali Radix, Radix Angelicae Sinensis, Rheum Officinale Baill, and four other herbs. In this study, we identified that SYFSF treatment prevented weight gain, low-grade inflammation and insulin resistance in high-fat diet (HFD)-fed mice. SYFSF also substantially improved gut barrier function, reduced metabolic endotoxemia, as well as systemic inflammation. Sequencing of 16S rRNA genes obtained from fecal samples demonstrated that SYFSF attenuated HFD-induced gut dysbiosis, seen an decreased Firmicutes to Bacteroidetes ratios. Microbial richness and diversity were also higher in the SYFSF-treated HFD group. Furthermore, similar therapeutic effects and changes in gut microbiota profile caused by SYFSF could be replicated by fecal microbiota transfer (FMT). Taken together, our study highlights the efficacy of SYFSF in preventing obesity and related metabolic disorders. Its therapeutic effect is associated with the modulation of gut microbiota, as a prebiotic.

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Intestinal Mucosal Barrier Function Restoration in Mice by Maize Diet Containing Enriched Flavan-4-Ols

Nutrients ◽

10.3390/nu12040896 ◽

2020 ◽

Vol 12 (4) ◽

pp. 896 ◽

Cited By ~ 1

Author(s):

Binning Wu ◽

Rohil Bhatnagar ◽

Vijaya V. Indukuri ◽

Shara Chopra ◽

Kylie March ◽

...

Keyword(s):

Barrier Function ◽

Control Diet ◽

Intestinal Barrier ◽

Mucosal Barrier ◽

Intestinal Barrier Function ◽

Low Grade ◽

Colonic Inflammation ◽

Mucosal Barrier Function ◽

Inflammatory Bowel ◽

Histology Score

Inflammatory bowel disease (IBD), a chronic intestinal inflammatory condition, awaits safe and effective preventive strategies. Naturally occurring flavonoid compounds are promising therapeutic candidates against IBD due to their great antioxidant potential and ability to reduce inflammation and improve immune signaling mediators in the gut. In this study, we utilized two maize near-isogenic lines flavan-4-ols-containing P1-rr (F+) and flavan-4-ols-lacking p1-ww (F−) to investigate the anti-inflammatory property of flavan-4-ols against carboxymethylcellulose (CMC)-induced low-grade colonic inflammation. C57BL/6 mice were exposed to either 1% CMC (w/v) or water for a total of 15 weeks. After week six, mice on CMC treatment were divided into four groups. One group continued on the control diet. The second and third groups were supplemented with F+ at 15% or 25% (w/w). The fourth group received diet supplemented with F− at 15%. Here we report that mice consuming F+(15) and F+(25) alleviated CMC-induced increase in epididymal fat-pad, colon histology score, pro-inflammatory cytokine interleukin 6 expression and intestinal permeability compared to mice fed with control diet and F−(15). F+(15) and F+(25) significantly enhanced mucus thickness in CMC exposed mice (p < 0.05). These data collectively demonstrated the protective effect of flavan-4-ol against colonic inflammation by restoring intestinal barrier function and provide a rationale to breed for flavan-4-ols enriched cultivars for better dietary benefits.

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