Depletion of gut microbiota suppresses spontaneous ileitis in mice driven by mitochondrial dysfunction induced by Phb1 deficiency

• DOI: 10.1096/fasebj.2022.36.s1.r2996
• Publication Date: 2022-05-03T09:35:39Z
• Authors: Kibrom Alula; Arianne Theiss
• Keywords: Dysbiosis; Ileitis; Eubacterium

Dysbiosis in gut microbiota is associated with inflammatory bowel diseases (IBD), such as Crohn's disease. Prohibitin 1 (PHB1) a mitochondrial protein important optimal respiration and decreased biopsies from IBD patients. Intestinal epithelial dysfunction emerging an underlying contributor to inflammation IBD. Previous studies our laboratory have demonstrated that mice Phb1-deficiency the intestinal epithelium (Phb1iΔIEC ) manifest dysfunction, Paneth cell defects, spontaneous ileum penetrance of 87% at 12 weeks after inducing Phb1 deletion. This reduction abundance short chain acid (SCFA)-producing bacteria, Blautia, Roseburia, Ruminococcus, Coprococccus. However, little known whether dysbiosis driver or consequence ileitis during dysfunction. In present study, we hypothesized necessary induce dysfunction.Phb1iΔIEC control Phb1fl/fl littermates were co-housed treated broad spectrum antibiotics (ABX) (1 g/L ampicillin sodium salt, neomycin sulfate, metronidazole, 500 mg/L vancomycin) autoclaved drinking water for 4 beginning 8 induction Ileal stools collected 16S rRNA sequencing quantification SCFAs by liquid chromatography-mass spectrometry. Ileum was histological (inflammation) scoring H&E staining immunofluorescent lysozyme Muc2 quantitate defects (lysozyme allocation patterns, increase lysozyme+/Muc2+ staining, crypts devoid lysozyme+ cells). Spleen weight also measured time sacrifice.Ileal stool Phb1iΔIEC exhibited significant SCFA butyrate compared littermates. showed ABX treatment abolished ileal bacterial population both mice. ameliorated enlarged spleen weights, inflammation, characteristic measurements noted mice.These results suggest IECs on its own not sufficient cause but triggers disease when coupled interaction. especially relevant given prevalence these