Successful Manipulation of the Gut Microbiome to Treat Spontaneous and Induced Murine Models of Colitis

成功操纵肠道微生物组来治疗小鼠自发性和诱发性结肠炎模型

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作者:Ramya Movva, Nida Murtaza, Rabina Giri, Chin Wen Png, Julie Davies, Saleh Alabbas, Iulia Oancea, Páraic O'Cuiv, Mark Morrison, Jakob Begun, Timothy H Florin

Aims

There is clinical interest in the sustainability or otherwise of prebiotic, microbial, and antibiotic treatments to both prevent and treat inflammatory bowel diseases. This study examined the role of antibiotic manipulation of the gut microbiome to treat spontaneous and induced murine models of colitis.

Background and aims

There is clinical interest in the sustainability or otherwise of prebiotic, microbial, and antibiotic treatments to both prevent and treat inflammatory bowel diseases. This study examined the role of antibiotic manipulation of the gut microbiome to treat spontaneous and induced murine models of colitis.

Conclusion

The results clearly show the possibility of a sustained remission of colitis by microbial manipulation, which is relevant to clinical management of inflammatory bowel diseases. The beneficial effects appeared to depend on the microbial metabolome rather than its taxonomy.

Methods

Symptomatic, histological, molecular, and microbial ecology and bioinformatic readouts were used to study the effect of a 10-day antibiotic cocktail and then follow-up over 2 months in the spontaneous Winnie colitis mouse preclinical model of ulcerative colitis and also the indirect antibiotic and Winnie microbiotic gavage effects in an acute dextran sodium sulfate-induced colitis model in wild-type mice.

Results

The antibiotics elicited a striking reduction in both colitis symptoms and blinded histological colitis scores, together with a convergence of the microbial taxonomy of the spontaneous colitis and wild-type control mice, toward a taxonomic phenotype usually considered to be dysbiotic. The improvement in colitis was sustained over the following 8 weeks although the microbial taxonomy changed. In vitro, fecal waters from the antibiotic-treated colitis and wild-type mice suppressed the inflammatory tenor of colonic epithelial cells, and gavaged cecal slurries from these mice moderated the acute induced colitis.

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