Effect of resveratrol on intestinal tight junction proteins and the gut microbiome in high-fat diet-fed insulin resistant mice

ABSTRACT Background Obesity, a major public health problem worldwide, is associated with dysfunction of the intestinal barrier. Glycine (Gly) has been reported to enhance the expression of tight-junction proteins in porcine enterocytes. It is unknown whether Gly can improve intestinal barrier integrity in obese mice. Objectives This study tested the hypothesis that Gly enhances the intestinal epithelial barrier by regulating endoplasmic reticulum (ER) stress–related signaling and mitigating inflammation in high-fat diet (HFD)-induced obese mice. Methods Five-week-old male C57BL/6J mice were fed a normal-fat diet (ND; fat = 10% energy) or an HFD (fat = 60% energy) and received drinking water supplemented with 2% Gly or 2.37% l-alanine (Ala; isonitrogenous control) daily for 12 wk. Body weight gain and tissue weights, glucose tolerance and the activation of immune cells, as well as the abundances of tight-junction proteins, ER stress proteins, and apoptosis-related proteins in the jejunum and colon were determined. In addition, the body weights of naïve ND and HFD groups (nND and nHFD, respectively) were also recorded for comparison. Differences were analyzed statistically by ANOVA followed by the Duncan multiple-comparison test using SAS software. Results Compared with ND-Ala, HFD-feeding resulted in enhanced macrophage (CD11b+ and F4/80+) infiltration and immune cell activation by 1.9- to 5.4-fold (P < 0.05), as well as the upregulation of ER stress sensor proteins (including phospho-inositol-requiring enzyme 1α and binding immunoglobulin protein) by 2.5- to 4.5-fold, the induction of apoptotic proteins by 1.5- to 3.2-fold, and decreased abundances of tight-junction proteins by 35%–65% (P < 0.05) in the intestine. These HFD-induced abnormalities were significantly ameliorated by Gly supplementation in the HFD-Gly group (P < 0.05). Importantly, Gly supplementation also significantly enhanced glucose tolerance (P < 0.05) by 1.5-fold without affecting the fat accumulation of HFD-induced obese mice. Conclusions Gly supplementation enhanced the intestinal barrier and ameliorated inflammation and insulin resistance in HFD-fed mice. These effects of Gly were associated with reduced ER stress–related apoptosis in the intestine of obese mice.

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Monobutyrin and Monovalerin Affect Brain Short-Chain Fatty Acid Profiles and Tight-Junction Protein Expression in ApoE-Knockout Rats Fed High-Fat Diets

Nutrients ◽

10.3390/nu12041202 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1202 ◽

Cited By ~ 1

Author(s):

Thao Duy Nguyen ◽

Frida Fåk Hållenius ◽

Xue Lin ◽

Margareta Nyman ◽

Olena Prykhodko

Keyword(s):

Tight Junction ◽

Hdl Cholesterol ◽

Short Chain ◽

Liver Cholesterol ◽

Tight Junction Proteins ◽

High Fat ◽

High Fat Diets ◽

Fat Diets ◽

The Brain ◽

Junction Proteins

Monobutyrin (MB) and monovalerin (MV), esters of short-chain fatty acids (SCFAs), have previously been shown to reduce liver cholesterol and inflammation in conventional rats fed high-fat diets. This study explored the potential effects of MB and MV in hypercholesterolemic apolipoprotein E-knockout (ApoE-/-) rats. ApoE-/- rats were fed three high-fat (HF) diets, pure or supplemented with MB or MV (1%), for 5 weeks. One group of conventional rats (C) was also fed the pure high-fat diet and another group of ApoE-/- rats a low-fat (LF) diet. Blood and liver lipids, urinary lactulose/mannitol, SCFAs (blood and brain), tight junction proteins (small intestine and brain), and inflammation-related markers (blood, brain, and liver) were analyzed. MV supplementation elevated serum high-density lipoprotein (HDL) cholesterol and valeric acid concentration (p < 0.05), while the amounts of isovaleric acid in the brain were reduced (p < 0.05). MB increased butyric acid amounts in the brain, while the plasma concentration of interleukin 10 (IL-10) was lowered (p < 0.05). Both MV and MB upregulated the expression of occludin and zonula occludens-1 (ZO-1) in the brain (p < 0.05). Supplementation of MB or MV affected HDL cholesterol, the expression of tight junction proteins, and SCFA profiles. MB and MV may therefore be promising supplements to attenuate lipid metabolic disorders caused by high-fat intake and genetic deficiency.

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Disruption of the pro-inflammatory, anti-inflammatory cytokines and tight junction proteins expression, associated with changes of the composition of the gut microbiota in patients with irritable bowel syndrome

PLoS ONE ◽

10.1371/journal.pone.0252930 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252930

Author(s):

V. Ivashkin ◽

Y. Poluektov ◽

E. Kogan ◽

O. Shifrin ◽

A. Sheptulin ◽

...

Keyword(s):

Tight Junction ◽

Healthy Volunteers ◽

Gut Microbiome ◽

Low Grade ◽

Tight Junction Proteins ◽

Microbiome Composition ◽

Tnf Α ◽

Irritable Bowel ◽

Low Grade Inflammation ◽

Junction Proteins

Background Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet. Aim of the study To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers. Methods In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-α in mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients. Results The expression of IL-2 and TNF-α was significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05). Conclusion IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.

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Gut microbiome induces leaky gut and inflammation by activating miRNAs which in turn reduces tight junction proteins

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.05274 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1

Author(s):

Sidharth P. Mishra ◽

Ravinder Nagpal ◽

Atefeh P. Razazan ◽

Bo Wang ◽

Hariom Yadav

Keyword(s):

Tight Junction ◽

Gut Microbiome ◽

Leaky Gut ◽

Tight Junction Proteins ◽

Junction Proteins

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Supplementation of Kiwifruit Polyphenol Extract Attenuates High Fat Diet Induced Intestinal Barrier Damage and Inflammation via Reshaping Gut Microbiome

Frontiers in Nutrition ◽

10.3389/fnut.2021.702157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Minlan Yuan ◽

Xiao Chen ◽

Tianxia Su ◽

Yan Zhou ◽

Xiaohong Sun

Keyword(s):

Tight Junction ◽

Relative Abundance ◽

Negative Correlation ◽

Gut Microbiome ◽

Barrier Function ◽

High Fat Diet ◽

Intestinal Barrier ◽

High Fat ◽

Tnf Α ◽

Junction Protein

Background: Impaired intestinal integrity and barrier function is associated with various diseases, including inflammatory bowel disease and metabolic syndrome. In recent years, plant-derived polyphenols have attracted much attention on regulating intestinal barrier function. Kiwifruit was recorded as a traditional Chinese medicine which can treat gastrointestinal diseases, but the mechanism was still unclear. In this study we investigated the effects of kiwifruit polyphenol extracts (KPE) on high fat diet induced intestinal permeability and its possible mechanism.Results: Dietary supplementation of KPE with 50 or 100 mg/kg bw could inhibit the increase of intestinal permeability caused by HFD and promote the expression of tight junction protein (Claudin-1, Occludin and ZO-1). From microbial diversity and RT-PCR, KPE administration reshaping gut microbiome, the relative abundance of Lactobacillus and Bifidobacterium were increased, and the relative abundance of Clostridium and Desulfovibrionaceae were decreased. The changes in microbe may influence intestinal inflammatory status. Then the expression of TLRs and cytokines were detected. KPE supplementation showed anti-inflammatory effect, the expression of IL-10 was increased and the expression of TLR-2, TLR-4, TNF-α and IL-1β were decreased. Correlation analysis indicated that the expression of tight junction protein was negative correlation with TLR-2, TLR-4, TNF-α and IL-1β expression, but positively correlated with Bacteroidete, Bifidobacterium and IL-10 expression; the expression of Bacteroidete, Lactobacillusand and Bifidobacterium were negative correlation with TLR4, TNF-α, and IL-1β expression.Conclusion: KPE treatment relieve the intestinal damage caused by HFD, which was related to the regulation of Bacteroidete, Lactobacillusand, and Bifidobacterium expression and inhibit intestinal inflammation. KPE could be a functional component for preventing gut damage and its related disease.

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Dietary copper-fructose interactions alter gut microbial activity in male rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00378.2016 ◽

2018 ◽

Vol 314 (1) ◽

pp. G119-G130 ◽

Cited By ~ 16

Author(s):

Ming Song ◽

Xiaohong Li ◽

Xiang Zhang ◽

Hongxue Shi ◽

Miriam B. Vos ◽

...

Keyword(s):

Liver Injury ◽

Tight Junction ◽

Gut Microbiome ◽

Deionized Water ◽

Tight Junction Proteins ◽

Gut Barrier ◽

Dietary Copper ◽

High Copper ◽

High Fructose ◽

Junction Proteins

Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and high-copper diets led to liver injury in high-fructose-fed rats, and this was associated with gut barrier dysfunction, as shown by the markedly decreased tight junction proteins and increased gut permeability. 16S rDNA sequencing analysis revealed distinct alterations of the gut microbiome associated with dietary low- and high-copper/high-fructose feeding. The common features of the alterations of the gut microbiome were the increased abundance of Firmicutes and the depletion of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our data demonstrated that a complex interplay among host, microbes, and dietary copper-fructose interaction regulates gut microbial metabolic activity, which may contribute to the development of liver injury and hepatic steatosis. The distinct alterations of gut microbial activity, which were associated with the different dietary doses of copper and fructose, imply that separate mechanism(s) may be involved.NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose-induced liver injury are associated with distinct alterations of gut microbiome. Second, dietary copper level plays a critical role in maintaining the gut barrier integrity, likely by acting on the intestinal tight junction proteins and the protective commensal bacteria Akkermansia. Third, the alterations of gut microbiome induced by dietary low and high copper with or without fructose differ mainly within the phylum Firmicutes.

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