Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: Impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-κB pathway

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

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Phillygenin Attenuates Carbon Tetrachloride-Induced Liver Fibrosis via Modulating Inflammation and Gut Microbiota

Frontiers in Pharmacology ◽

10.3389/fphar.2021.756924 ◽

2021 ◽

Vol 12 ◽

Author(s):

Cheng Wang ◽

Cheng Ma ◽

Ke Fu ◽

Li-Hong Gong ◽

Ya-Fang Zhang ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Liver Function ◽

Gut Microbiota ◽

Epithelial Barrier ◽

Rrna Gene ◽

Intestinal Epithelial ◽

Collagen Deposition ◽

Intestinal Epithelial Barrier ◽

Corrective Effect

Liver fibrosis is a chronic pathological process that various pathogenic factors lead to abnormal hyperplasia of hepatic connective tissue, and its main feature is the excessive deposition of extracellular matrix. However, there are currently no drugs approved for the treatment of liver fibrosis. Phillygenin (PHI), a lignan isolated from Forsythiae Fructus, showed potential anti-inflammatory and anti-fibrosis effects but the mechanisms remain unknown. In view of the vital role of gut microbiota in the development of liver fibrosis, this study aimed to explore whether PHI could protect intestinal epithelial barrier and attenuate liver fibrosis by maintaining the homeostasis of intestinal microbiota. Therefore, the liver fibrosis model was induced by intraperitoneal injection of olive oil containing 10% carbon tetrachloride (CCl4) for 4 weeks in C57BL/6J mice. Histological analysis including Hematoxylin-Eosin, Masson, Sirius red, and immunohistochemistry staining were carried out to detect the histopathology and collagen deposition of mice liver tissues. The biochemical indexes related to liver function (ALT, AST, AKP, γ-GT), fibrosis (HYP, HAase, LN, PC III, IV-C) and inflammation (TNF-α, MIP-1, LPS) were determined by specific commercial assay kits. In vivo experimental results showed that PHI could improve liver histopathological injury, abnormal liver function, collagen deposition, inflammation and fibrosis caused by CCl4. Moreover, PHI restored the intestinal epithelial barrier by promoting the expression of intestinal barrier markers, including ZO-1, Occludin and Claudin-1. More importantly, the corrective effect of PHI on the imbalance of gut microbiota was confirmed by sequencing of the 16 S rRNA gene. In particular, PHI treatment enriches the relative abundance of Lactobacillus, which is reported to alleviate inflammation and fibrosis of damaged liver. Collectively, PHI attenuates CCl4-induced liver fibrosis partly via modulating inflammation and gut microbiota.

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Effects of dietary fibers and prebiotics in adiposity regulation via modulation of gut microbiota

Applied Biological Chemistry ◽

10.1186/s13765-019-0482-9 ◽

2020 ◽

Vol 63 (1) ◽

Cited By ~ 2

Author(s):

Adriana Rivera-Piza ◽

Sung-Joon Lee

Keyword(s):

Metabolic Disease ◽

Gut Microbiota ◽

Metabolic Disorders ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Dietary Fibers ◽

Intestinal Epithelial Barrier ◽

Gut Homeostasis ◽

Gut Microorganisms

AbstractThe microbiota is indispensable for human health and the regulation of various body functions, including energy metabolism. The harmonic crosstalk between the microbiota and the intestinal epithelial barrier determines gut homeostasis and health status in the healthy subject. Obesity and type 2 diabetes risk are, to some extent, explained by alterations in the microbiota. Since recent data indicate that the population of gut microorganisms can influence nutrient absorption and energy storage thus prevalence on obesity and metabolic disorders. Moreover, metabolic disease conditions, such as obesity, may be stimulated by genetic, environmental factors and by pathways that link metabolism with the immune system. On the basis of the above considerations, this review compiles the current results obtained in recent studies indicating the gut microbiota contribution to obesity development.

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The Impact of Gut Microbiota on Radiation-Induced Enteritis

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.586392 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yongping Jian ◽

Dan Zhang ◽

Mingdi Liu ◽

Yishu Wang ◽

Zhi-Xiang Xu

Keyword(s):

Escherichia Coli ◽

Gut Microbiota ◽

Radiation Enteritis ◽

Epithelial Barrier ◽

Inflammatory Factor ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Radiation Induced ◽

The Impact ◽

Gut Microbiota Dysbiosis

Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in radiation enteritis, in particular the role of gut microbiota dysbiosis in the development and therapy of the disease. Gut microbiota dysbiosis plays an important role in the occurrence of various diseases, such as radiation enteritis. Abdominal radiation results in changes in the composition of microbiota and reduces its diversity, which is mainly reflected in the decrease of Lactobacillus spp. and Bifidobacterium spp. and increase of Escherichia coli and Staphylococcus spp. Gut microbiota dysbiosis aggravates radiation enteritis, weakens intestinal epithelial barrier function, and promotes inflammatory factor expression. Pathogenic Escherichia coli induce the rearrangement and redistribution of claudin-1, occludin, and ZO-1 in tight junctions, a critical component in intestinal epithelial barrier. In view of the role that microbiome plays in radiation enteritis, we believe that intestinal flora could be a potential biomarker for the disease. Correction of microbiome by application of probiotics, fecal microbiota transplantation (FMT), and antibiotics could be an effective method for the prevention and treatment of radiation-induced enteritis.

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Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in cardiovascular disease

Clinical Science ◽

10.1042/cs20180172 ◽

2018 ◽

Vol 132 (8) ◽

pp. 901-904 ◽

Cited By ~ 13

Author(s):

Judith N. Lezutekong ◽

Anish Nikhanj ◽

Gavin Y. Oudit

Keyword(s):

Cardiovascular Disease ◽

Gut Microbiota ◽

Intestinal Barrier ◽

Epithelial Barrier ◽

Main Function ◽

Intestinal Epithelial ◽

Barrier Dysfunction ◽

Intestinal Epithelial Barrier ◽

Physiological Homeostasis ◽

Epithelial Barrier Dysfunction

The main function of the intestinal barrier is to regulate the absorption of nutrients, electrolytes, and water from the lumen into circulation and to prevent the entry of pathogenic microorganisms and toxic luminal substances. To maintain this function, an ideal microbiota balance is required and gut microbiota are critical for the intestinal epithelial barrier dysfunction and for the maintenance of physiological homeostasis. There is a demonstrable link between dysbiosis and intestinal dysfunction and diseases such as diabetes, obesity, and cardiovascular disease. However, links amongst gut pathology, microbial ecology, and blood pressure remain elusive. In a recent issue of Clinical Science (vol. 132, issue 6, 701-718), Kim et al. demonstrate a crucial link between gut microbiota and bacterial metabolites such as butyrate, gut leakiness, and hypertension.

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Blueberry Attenuates Liver Fibrosis, Protects Intestinal Epithelial Barrier, and Maintains Gut Microbiota Homeostasis

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2019/5236149 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Zhiqiang Yan ◽

Fang Yang ◽

Zhu Hong ◽

Shishun Wang ◽

Zhang Jinjuan ◽

...

Keyword(s):

Body Weight ◽

Liver Fibrosis ◽

Gut Microbiota ◽

Tight Junction ◽

Rat Liver ◽

Liver Weight ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Junction Protein

Objective. Recently, blueberry has been identified as a candidate for the treatment of liver fibrosis. Given the role of gut-liver axis in liver fibrosis and the importance of the gut microbiota homeostasis to the maintenance of the intestinal epithelial barrier, this study aimed to investigate whether blueberry could attenuate liver fibrosis and protect the intestinal epithelial barrier by maintaining the homeostasis of the gut microbiota. Method. A CCl4-induced rat liver fibrosis model was used to detect the roles of blueberry in liver fibrosis and intestinal epithelial barrier. The liver weight and body weight were measured, the liver function was monitored by ALT and AST activity, protein and mRNA were determined by western blot and RT-qPCR, and the gut microbiome was detected by Miseq. Results. The results showed that blueberry could reduce the rate of liver weight/body weight gain (p<0.05), ALT (p<0.01) and AST (p<0.05) activity, and the expression of collagen I (p<0.01), collagen IV (p<0.01), and α-SMA (p<0.01) expression in CCl4-induced rat liver. CCl4 impaired the intestinal epithelial barrier and decreased the expression of the tight junction protein. Blueberry restored the intestinal epithelial barrier and increased the expression of the tight junction protein. The gut microbiota homeostasis was impaired by CCl4, but after treatment with blueberry, the intestinal flora returned to normal. Conclusion. Blueberry attenuated liver fibrosis, protected intestinal epithelial barrier, and maintained the homeostasis of the gut microbiota in a CCl4-induced injury rat model.

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Next Generation Microbiome Research: Identification of Keystone Species in the Metabolic Regulation of Host-Gut Microbiota Interplay

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.719072 ◽

2021 ◽

Vol 9 ◽

Author(s):

Héloïse Tudela ◽

Sandrine P. Claus ◽

Maya Saleh

Keyword(s):

Gut Microbiota ◽

Metabolic Regulation ◽

Keystone Species ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Nutrient Metabolism ◽

Major Step ◽

Microbiome Research ◽

Health And Disease

The community of the diverse microorganisms residing in the gastrointestinal tract, known as the gut microbiota, is exceedingly being studied for its impact on health and disease. This community plays a major role in nutrient metabolism, maintenance of the intestinal epithelial barrier but also in local and systemic immunomodulation. A dysbiosis of the gut microbiota, characterized by an unbalanced microbial ecology, often leads to a loss of essential functions that may be associated with proinflammatory conditions. Specifically, some key microbes that are depleted in dysbiotic ecosystems, called keystone species, carry unique functions that are essential for the balance of the microbiota. In this review, we discuss current understanding of reported keystone species and their proposed functions in health. We also elaborate on current and future bioinformatics tools needed to identify missing functions in the gut carried by keystone species. We propose that the identification of such keystone species functions is a major step for the understanding of microbiome dynamics in disease and toward the development of microbiome-based therapeutics.

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