Our work revealed that A. muciniphila attenuated APAP-induced liver injury by alleviating oxidative stress and inflammation in the liver, and its hepatoprotective effect was accompanied by activation of the PI3K/Akt pathway and mediated by regulation of the composition and metabolic function of the intestinal microbiota. This finding suggested that the microbial community is a non-negligible impact on drug metabolism and probiotic administration could be a potential therapy for drug-induced liver injury.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease with a high incidence. Multiple factors including dietary composition contribute to its occurrence. Recently, ketogenic diet which consists of a high proportion of fat and low carbohydrates has gained great popularity. Our study is aimed to explore the effect of ketogenic diet on IBD and its potential mechanisms. C57BL/6 mice were given a ketogenic diet or a control diet for a month and IBD was induced by 2% DSS in drinking water in the last week. Gut histology, inflammatory cytokines and chemokines, gut microbiota and metabolism were assessed. Ketogenic diet substantially worsened colitis, in terms of higher body weight loss, DAI scores and histological scores as well as colon length shortening. Levels of serum and colon inflammatory cytokines and chemokines (IL-1α, IL-6, TNF-α, IL-17, GM-CSF and IL-10) were significantly up-regulated in mice treated with ketogenic diet and DSS. Increased intestinal permeability and decreased expressions of intestinal epithelial barrier associated genes were observed due to ketogenic diet administration. Pretreatment with ketogenic diet alters the bacterial abundance, increasing pathogenic taxa such as Proteobacteria, Enterobacteriaceae, Helicobacter and Escherichia-Shigella and decreasing potential beneficial taxa such as Erysipelotrichaceae. Ketogenic diet also modified gut metabolism, increasing metabolites in the bile secretion such as ouabain, taurochenodeoxycholic acid, quinine, cholic acid and glycocholic acid, and decreasing metabolites associated with the biosynthesis of unsaturated fatty acids including stearic acid, arachidic acid, erucic acid, and docosanoic acid. These results suggest that ketogenic diet aggravates DSS-induced colitis in mice by increasing intestinal and systemic inflammation, and disrupting the intestinal barrier, which results from modulated gut microbiota and metabolism.

Akkermansia muciniphila attenuated lipopolysaccharide-induced acute lung injury by modulating the gut microbiota and SCFAs in mice.

Summary: Millions of people die from liver diseases annually, and liver failure is one of the three major outcomes of liver disease. The gut microbiota plays a crucial role in liver diseases. This study aimed to explore the effects of Lactobacillus casei strain Shirota (LcS), a probiotics used widely around the world, on acute liver injury (ALI), as well as the underlying mechanism. Sprague Dawley rats were intragastrically administered LcS suspensions or placebo once daily for 7 days before induction of ALI by intraperitoneal injection of D‐galactosamine (D‐GalN). Histopathological examination and assessments of liver biochemical markers, inflammatory cytokines, and the gut microbiota, metabolome and transcriptome were conducted. Our results showed that pretreatment with LcS reduced hepatic and intestinal damage and reduced the elevation of serum gamma‐glutamyltranspeptidase (GGT), total bile acids, IL‐5, IL‐10, G‐CSF and RANTES. The analysis of the gut microbiota, metabolome and transcriptome showed that LcS lowered the ratio of Firmicutes to Bacteroidetes; reduced the enrichment of metabolites such as chenodeoxycholic acid, deoxycholic acid, lithocholic acid, d ‐talose and N ‐acetyl‐glucosamine, reduce the depletion of d ‐glucose and l ‐methionine; and alleviated the downregulation of retinol metabolism and PPAR signalling and the upregulation of the pyruvate metabolism pathway in the liver. These results indicate the promising prospect of using LcS for the treatment of liver diseases, particularly ALI.