Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites

Gut, Journal Year: 2020, Volume and Issue: 70(4), P. 761 - 774

Published: July 21, 2020

Objective Non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is an increasing healthcare burden worldwide. We examined the role of dietary cholesterol in driving NAFLD–HCC through modulating gut microbiota and its metabolites. Design High-fat/high-cholesterol (HFHC), high-fat/low-cholesterol or normal chow diet was fed to C57BL/6 male littermates for 14 months. Cholesterol-lowering drug atorvastatin administered HFHC-fed mice. Germ-free mice were transplanted with stools from different diets determine direct modulated-microbiota NAFLD–HCC. Gut analysed by 16S rRNA sequencing serum metabolites liquid chromatography–mass spectrometry (LC–MS) metabolomic analysis. Faecal microbial compositions 59 hypercholesterolemia patients 39 healthy controls. Results High led sequential progression steatosis, steatohepatitis, fibrosis eventually HCC mice, concomitant insulin resistance. Cholesterol-induced formation associated dysbiosis. The composition clustered distinctly along stages steatohepatitis HCC. Mucispirillum, Desulfovibrio, Anaerotruncus Desulfovibrionaceae increased sequentially; while Bifidobacterium Bacteroides depleted which corroborated human hypercholesteremia patients. Dietary induced bacterial alteration including taurocholic acid decreased 3-indolepropionic acid. gavaged HFHC manifested hepatic lipid accumulation, inflammation cell proliferation. Moreover, restored cholesterol-induced dysbiosis completely prevented development. Conclusions drives inducing Cholesterol inhibitory therapy manipulation may be effective strategies prevention.

Language: Английский

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Roles of intestinal epithelial cells in the maintenance of gut homeostasis

Experimental & Molecular Medicine, Journal Year: 2017, Volume and Issue: 49(5), P. e338 - e338

Published: May 1, 2017

The intestine is a unique organ inhabited by tremendous number of microorganisms. Intestinal epithelial cells greatly contribute to the maintenance symbiotic relationship between gut microbiota and host constructing mucosal barriers, secreting various immunological mediators delivering bacterial antigens. Mucosal including physical barriers chemical spatially segregate immune system avoid unnecessary responses microbes, leading intestinal inflammation. In addition, mediators, cytokines chemokines, secreted from stimulated modulate responses, maintaining well-balanced microbes system. Therefore, impairment innate functions associated with A review researchers in Japan highlights how moderate interactions foreign Epithelial line surface gut, separating body's that enter body food. Drawing on numerous recent studies, Ryu Okamura Kiyoshi Takeda at Osaka University identify two main roles perform maintain healthy balance gut. Firstly, barriers. Secondly, they mediate passing information system, triggering where necessary. Understanding role these important given increasing evidence defects their are strongly related inflammatory bowel problems such as ulecerative colitis.

Language: Английский

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Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Feb. 26, 2021

Hosting millions of microorganisms, the digestive tract is primary and most important part bacterial colonization. On one side, in cases opportunistic invasion, abundant population inside intestinal tissues may face potential health problems such as inflammation infections. Therefore, immune system has evolved to sustain host–microbiota symbiotic relationship. other hand, maintain host homeostasis, microflora often exerts an immunoregulatory function that cannot be ignored. A field great interest association either microbiota or probiotics with concerning clinical uses. This microbial community regulates some host’s metabolic physiological functions drives early-life maturation, contributing their homeostasis throughout life. Changes gut can occur through modification function, composition (dysbiosis), microbiota–host interplays. Studies on animals humans show have a pivotal effect modulation inflammatory mechanisms; however, precise mechanisms not yet been well defined. Diet, age, BMI (body mass index), medications, stress confound benefits probiotic intake. In addition (permeability physiology), all these agents profound implications for microbiome composition. The use could improve population, increase mucus-secretion, prevent destruction tight junction proteins by decreasing number lipopolysaccharides (LPSs). When LPS binds endothelial cells toll-like receptors (TLR 2, 4), dendritic macrophage are activated, markers increased. Furthermore, decrease dysbiosis leakage after therapy minimize development biomarkers blunt unnecessary activation system. turn, differentiation T-cells against Th2 cytokines IL-4 IL-10. present narrative review explores interactions between microflora/probiotics starting from general perspective biological plausibility get vitro vivo demonstrations probiotic-based approach up possible uses novel therapeutic strategies.

Language: Английский

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Interaction Between the Microbiota, Epithelia, and Immune Cells in the Intestine

Annual Review of Immunology, Journal Year: 2020, Volume and Issue: 38(1), P. 23 - 48

Published: April 26, 2020

The gastrointestinal tract harbors numerous commensal bacteria, referred to as the microbiota, that benefit host health by digesting dietary components and eliminating pathogens. intestinal microbiota maintains epithelial barrier integrity shapes mucosal immune system, balancing defense oral tolerance with microbial metabolites, components, attachment cells. To avoid aberrant responses, cells segregate from constructing chemical physical barriers, leading establishment of host-commensal mutualism. Furthermore, participate in maintenance a healthy community reinforce functions. Perturbations composition are commonly observed patients autoimmune diseases chronic inflammatory disorders. An understanding intimate interactions between cells, crucial for homeostasis might promote advances diagnostic therapeutic approaches various diseases.

Language: Английский

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Gut microbiome interactions with drug metabolism, efficacy, and toxicity

Translational research, Journal Year: 2016, Volume and Issue: 179, P. 204 - 222

Published: Aug. 15, 2016

Language: Английский

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