Gut Microbiota Deficiency Exacerbates Liver Injury in Bile Duct Ligated Mice via Inflammation and Lipid Metabolism

Abstract

Bile components play a critical role in maintaining gut microbiota homeostasis. In cholestasis, bile secretion is impaired, leading to liver injury. However, it remains to be elucidated whether gut microbiota plays a role in cholestatic liver injury. Here, we performed a sham operation and bile duct ligation (BDL) in antibiotic-induced microbiome depleted (AIMD) mice and assessed liver injury and fecal microbiota composition in these mice. Significant reductions in gut microbiota richness and diversity were found in AIMD-sham mice when compared to sham controls. Three-day BDL leads to great elevation of plasma ALT, ALP, total bile acids, and bilirubin where reduced diversity of the gut microbiota was also found. AIMD further aggravated cholestatic liver injury evidenced by significantly higher levels of plasma ALT and ALP, associated with further reduced diversity and increased Gram-negative bacteria in gut microbiota. Further analyses revealed increased levels of LPS in the plasma of AIMD-BDL mice where elevated expression of inflammatory genes and decreased expression of hepatic detoxification enzymes were also found in liver when compared to the BDL group. These findings indicate that gut microbiota plays a critical role in cholestatic liver injury. Maintaining its homeostasis may alleviate liver injury in patients with cholestasis.

High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Micropterus salmoides)

“…Considering the lower levels of serum ALB in D7 groups, it indicated that high dietary starch could impair immunity and increase the danger of oxidative stress in largemouth bass. Previous studies have found higher levels of serum TBA could be correlated with early-stage metabolic liver disease mediated by higher contents of cholesterol in animals [37,64]. Therefore, elevated levels of serum TBA suggest that increased dietary starch not only worsens liver damage but also triggers cholestatic disease in largemouth bass [65,66].…”