Zuogui-Jiangtang-Qinggan-Fang alleviates high-fat diet-induced type 2 diabetes mellitus with non-alcoholic fatty liver disease by modulating gut microbiome-metabolites-short chain fatty acid composition

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Abstract

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d1049673e123">Non-alcoholic fatty liver disease (NAFLD) pathogenesis is affected by dysbiosis of the gut microbiome and the metabolites it generates. Therefore, restoring the equilibrium between the gut microbiome and the generated metabolites may have therapeutic potential for the syndrome. Zuogui Jiangtang Qinggan Fang (ZGJTQGF) is a Chinese herbal formulation used clinically to treat type 2 diabetic mellitus (T2DM) and fatty liver disease. However, its pharmacological mechanisms have not been well characterized. This work aimed to evaluate the hepatoprotective mechanism of ZGJTQGF in T2DM with NAFLD mice by incorporating gut microbiota, short-chain fatty acids（SCFAs）, and metabolomic analysis, and then to provide strong support for clinical treatment of T2DM with NAFLD. The sequencing of 16 S rRNA revealed that ZGJTQGF therapy modified the composition and abundance of the gut microbiome, raised the level of SCFAs, and restored the intestinal mucosal barrier. The non-targeted metabolomic analysis of liver tissues identified 212 compounds, of which108 were differentially expressed between the HFD and ZGJTQGF groups. Moreover, L-glutamic acid, L-Phenylalanine, Glycine, Taurine, Deoxycholic acid, and citric acid levels were also considerably altered by ZGJTQGF. Our findings suggest that ZGJTQGF ameliorates HFD-induced hepatic steatosis by modulating the gut microbiota composition and its metabolites and boosting the levels of SCFAs. More notably, ZGJTQGF may be a promising medication for preventing and treating NAFLD. </p>

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Gut microbial metabolites in obesity, NAFLD and T2DM

Emanuel E Canfora, Ruth Meex, Koen Venema … (2019)

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

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Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function.

Caleb J Kelly, Leon Zheng, Eric L Campbell … (2015)

Interactions between the microbiota and distal gut are fundamental determinants of human health. Such interactions are concentrated at the colonic mucosa and provide energy for the host epithelium through the production of the short-chain fatty acid butyrate. We sought to determine the role of epithelial butyrate metabolism in establishing the austere oxygenation profile of the distal gut. Bacteria-derived butyrate affects epithelial O2 consumption and results in stabilization of hypoxia-inducible factor (HIF), a transcription factor coordinating barrier protection. Antibiotic-mediated depletion of the microbiota reduces colonic butyrate and HIF expression, both of which are restored by butyrate supplementation. Additionally, germ-free mice exhibit diminished retention of O2-sensitive dyes and decreased stabilized HIF. Furthermore, the influences of butyrate are lost in cells lacking HIF, thus linking butyrate metabolism to stabilized HIF and barrier function. This work highlights a mechanism where host-microbe interactions augment barrier function in the distal gut.

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Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease

David Ipsen, Jens Lykkesfeldt, Pernille Tveden-Nyborg (2018)

Non-alcoholic fatty liver disease (NAFLD) is currently the world’s most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition exceeding lipid disposal, i.e., the uptake of fatty acids and de novo lipogenesis surpassing fatty acid oxidation and export. In NAFLD, hepatic uptake and de novo lipogenesis are increased, while a compensatory enhancement of fatty acid oxidation is insufficient in normalizing lipid levels and may even promote cellular damage and disease progression by inducing oxidative stress, especially with compromised mitochondrial function and increased oxidation in peroxisomes and cytochromes. While lipid export initially increases, it plateaus and may even decrease with disease progression, sustaining the accumulation of lipids. Fueled by lipo-apoptosis, hepatic steatosis leads to systemic metabolic disarray that adversely affects multiple organs, placing abnormal lipid metabolism associated with NAFLD in close relation to many of the current life-style-related diseases.