Klebsiella michiganasis as a tissue repairing commensal in gut inflammation

Abstract

Abstract Commensal bacteria are recognized as contributors for both tissue inflammation and tissue homeostasis. Therefore, we tested their potential for gut inflammation and tissue repairing using Germ-Free (GF) mice using stools from healthy human donors. Although, DSS-treated WT GF mice all die within 10 days due to severe colonic epithelial damage, gnotobiotic WT mice colonized with a healthy microbiome survived and carried more IL-22 producing innate and adaptive immune cells. This suggests that healthy stools contain wound healing commensals, however, IL10 KO mice with the same stools developed colitis, indicating a colitogenic potential. To eliminate colitogenic from wound healing commensals we utilized various antibiotics in human stool inoculated mice. These treated mice showed significant reductions in their microbiomes. Importantly, IFNg/IL-17A double producing pathogenic CD4 T cells were decreased leading to no colitis in gavaged IL10 KO mice. Additionally, gnotobiotic WT mice colonized with cecum contents from treated human stool gavaged IL10 KO survived lethal DSS treatment. We isolated Klebsiella michiganasis (K. michiganasis) from their cecum and confirmed that monocolonization of K. michiganasis in GF WT mice reproduced the wound healing ability via both the IL-23 and IL1b pathways stimulating type 3 innate lymphoid cells to strongly produce IL-22. Our results suggest that non-pathogenic K. michiganasis is a promising commensal for combating gut inflammation.