Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function

• DOI: 10.1016/j.jcmgh.2022.06.012
• Publication Date: 2022-07-08T07:02:26Z
• Authors: Sukanta Das; Zhuolun Song; Hui Han; Xiaodong Ge; Romain Desert; Dipti Athavale; Sai Santosh Babu ...; Fernando Magdaleno; Wei Chen; Daniel Lantvit; Grace Guzman; Natalia Nieto
• Keywords: Osteopontin; Intestinal Microbiome; Barrier function; Gut microbiome

Background & AimsThe gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn-/- develop worse ALD than wild-type (WT) mice; however, intestinal osteopontin (OPN) remains unknown. hypothesized overexpression OPN epithelial cells (IECs) could ameliorate by preserving gut microbiome and barrier function.MethodsOpnKI IEC, OpnΔIEC, WT mice were fed control or ethanol Lieber-DeCarli diet for 6 weeks.ResultsOpnKI IEC but not OpnΔIEC showed improved function protection from ALD. There less pathogenic more beneficial bacteria ethanol-fed OpnKI mice. Fecal transplant (FMT) to protected FMT failed induce Antimicrobial peptides, Il33, pSTAT3, aryl hydrocarbon receptor (Ahr), tight-junction protein expression higher IECs jejunum Ethanol-fed tryptophan metabolites short-chain fatty acids portal serum enhanced Ahr expression. Oral administration milk replicated protective effect ALD.ConclusionOverexpression maintain antimicrobial peptides. The increase signaling through IECs, preserve protect function. weeks. Overexpression