Intestinal ILC3 Activation by Commensal Bacteroides thetaiotaomicron: Implication for Liver Protection in Alcohol-Induced Liver Disease

Abstract

Abstract In recent years, there has been a growing recognition of the intricate interplay between the commensal bacteria Bacteroides thetaiotaomicron (Bt) and immune system. Among the various immune cell subsets, innate lymphoid cells (ILCs), group 3 ILCs (ILC3s) have particularly piqued the interest of researchers, as they appear to wield a significant influence in maintaining gut homeostasis. In order to understand if Bt mediates the crosstalk between intestinal epithelial cells (IECs) and ILC3 that prevents gut dysbiosis and liver injury in alcoholic liver disease (ALD), a disorder that causes lipid accumulation, liver damage, gut bacterial overgrowth and gastrointestinal mucosa dysfunctions, this study narrowed to the exploration of intricate relationship between Bt and ILC3s activation in the modulation of ALD. Bt supplementation leads to lower liver triglyceride content, prevent liver from steatosis, inflammatory lesions, relieves liver fat lesions and enhance intestinal. Bt enhances the Ahr activity and IL23 expression in IEC. The beneficial effect of Bt was abrogated in mice supplemented with Bt lacking capsular polysaccharides (CPS) and diminish AhR dependent IECs IL23 production and activation of type 3 innate lymphoid cells (ILC3). IL22-producing ILC3 cells improved gut homeostasis and this cascade ultimately results in enhance Mucin secretion, reduced systemic inflammation, hepatocyte apoptosis, and subsequently acute liver injury through the gut-liver axis.