Western Diet Aggravated Carbon Tetrachloride‐Induced Chronic Liver Injury by Disturbing Gut Microbiota and Bile Acid Metabolism

Abstract

Scope The high‐fat, high‐sucrose, and low‐fiber Western diet (WD) is popular in many countries and affects the onset and progression of many diseases. This study is aimed to explore the influence of the WD on chronic liver disease (CLD) and its possible mechanism. Methods and results C57BL/6 mice are given a control diet (CD) or WD and CLD is induced by intraperitoneally injecting carbon tetrachloride (CCL4) twice a week for 8 weeks. The WD aggravated CCL4‐induced chronic liver injury, as evidenced by increased serum transaminase levels, worsened hepatic inflammatory response, and fibrosis. Gut microbiota is disturbed in mice treated with CCL4+WD (WC group), manifested as the accumulation of Fusobacteria, Streptococcaceae, Streptococcus, Fusobacterium, and Prevotella and the depletion of Firmicutes, Lachnospiraceae, and Roseburia. Additionally, increased hepatic taurocholic acid in the WC group activated sphingosine‐1‐phosphate receptor 2, which is positively correlated with hepatic fibrosis and inflammation parameters. Mice in the WC group have higher fecal primary bile acid (BA) levels and lower fecal secondary/primary BA ratios. Serum FGF15 levels are also elevated in the WC group, which is positively correlated with hepatic inflammation. Conclusion WD accelerates the progression of CLD which is associated with changes in the gut microbiota and BA metabolism.

Flaxseed Powder Attenuates Non-Alcoholic Steatohepatitis via Modulation of Gut Microbiota and Bile Acid Metabolism through Gut–Liver Axis

“…A previous study showed that alteration in BA hydrophobicity through BSH deconjugating induced the expression of key genes related to lipid metabolism and transportation [ 51 ]. Supporting evidence showed that the abundances of Lactobacilli and Bifidobacterium had positive correlations with the secondary/primary BA ratio [ 52 ], and the abundance of Firmicutes was negatively associated with the secondary/primary BA ratio. Our results are consistent with the above-mentioned results that the abundance of Bifidobacterium increased in FLA-fed groups (middle and high dose) and Firmicutes decreased in all FLA-fed groups.…”

Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites

“…Bile acids (TCA, taurocholic acid; βMCA, β-muricholic acid; CA, cholic acid; αMCA, α-muricholic acid; UDCA, ursodeoxycholic acid; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; ωMCA, ω-muricholic acid; HDCA, hyodeoxycholic acid; muroCA, murocholic acid; βDCA, β-deoxycholic acid; and LCA, lithocholic acid) in colon contents were detected according to previously described protocol ( Xie et al, 2015 ; Yang et al, 2021 ) and purchased from Steraloids, Inc. (Newport, RI, United States). Briefly, colon contents were mixed with 200 μL acetonitrile/methanol (volume 8:2), which contained internal standards (GCA-d4, TCA-d4, GDCA-d4, CA-d4, DCA-d4, and LCA-d4).…”

Antarctic krill peptide alleviates liver fibrosis via downregulating the secondary bile acid mediated NLRP3 signaling pathway

“…30 Yang et al revealed that Bacteroidetes were enriched in the mouse model of fibrosis induced by a western diet combined with CCl4, while Firmicutes decreased. 31 Bajaj et al found a direct relationship between patients with cirrhosis and levels of Lactobacillaceae and Bifidobacterium. 9 Chen et al found that the degree of liver fibrosis is positively correlated with the richness of streptococcaceae but negatively correlated with the richness of Lachnospiraceae.…”