Change Of Gut Microbiota And The Susceptibility To Inflammatory Bowel Disease Under Early-life Subtherapeutic Antibiotic Treatment

Background and objective: The rising incidence of IBD indicates a significant effect of environmental risk factors,such as antibiotic consumption.Epidemiologic studies yielded contradicting results with respect to the relationship between early-life antibiotic treatment and later onset of IBD.We aim to examine the impact of subtherapeutic antibiotics on the gut microbiota,as well as the alteration of the immune system and the susceptibility to IBD,within an animal model.Methods: Three-week weanling mice were treated with low-does penicillin,metronidazole or enrofloxacin.Fecal microbiota composition was analyzed by 16 sRNA gene sequencing.Inflammation-related cytokine expression of terminal ileum,mesenteric lymph nodes(MLN)and Peyer's patches(PP)was examined by qPCR.Small-intestine lamina propria(SI-LP)lymphocyte differentiation was further studied with flow cytometry.To investigate the potential susceptibility alteration,mice were challenged with DSS after a one-week interval following antibiotic cessation.Results: Subtherapeutic penicillin and metronidazole caused a transient change of gut microbiota diversity,without an obvious sign of dysbacteriosis.These two antibiotics both caused specific phylogenic shifting.Compared with control and metronidazole,subtherapeutic penicillin specifically suppressed segmented filamentous bacteria(SFB),Allobaculum and Turicibacter.SFB can be suppressed by an even lower dose of penicillin at 0.1?g/g·d.Subtherapeutic penicillin treated mice had lower expression of IL17 in terminal ileum,MLN and PP,together with a decreased amount of SI-LP Th17 cells,which was related to the suppression of SFB.Neither metronidazole nor enrofloxacin had a similar effect.Mice treated with subtherapeutic penicillin also had a lower degree of inflammation when challenged with DSS.Conclusions: Subtherapeutic penicillin can down-regulate the expression of IL17 and decrease the amount of SI-LP Th17 cells.It also lowers the mice's susceptibility to DSS colitis.These effects may be caused by the alteration of gut microbiota,especially the suppression of SFB.