The Bactericidal Lectin RegIIIβ Prolongs Gut Colonization and Enteropathy in the Streptomycin Mouse Model for Salmonella Diarrhea

Publication date: Available online 19 January 2017
Source:Cell Host & Microbe
Author(s): Tsuyoshi Miki, Ryosuke Goto, Mayuka Fujimoto, Nobuhiko Okada, Wolf-Dietrich Hardt
The bactericidal lectin RegIIIβ is inducibly produced by intestinal epithelial cells as a defense against infection by enteropathogens. In the gut lumen, RegIIIβ kills not only certain enteropathogens, but also some commensal bacteria; thus, RegIIIβ is also thought to be an innate immune effector shaping microbiota composition and establishing intestinal homeostasis. Using the streptomycin mouse model for Salmonella colitis, we show that RegIIIβ can promote sustained gut colonization of Salmonella Typhimurium and prolong enteropathy. RegIIIβ expression was associated with suppression of Bacteroides spp. in the gut lumen, prolonged disease-associated alterations in colonic metabolism, and reduced luminal vitamin B6 levels. Supplementation with Bacteroides spp. or vitamin B6 accelerated pathogen clearance from the gut and remission of enteropathy. Our findings indicate that interventions at the level of RegIIIβ and supplementation with Bacteroides spp. or vitamin B6 might open new avenues for therapeutic intervention in the context of Salmonella colitis.

Graphical abstract

Teaser

Gut infection with enteropathogens elicits expression of the antimicrobial RegIIIβ lectin. Miki et al. find that RegIIIβ prolongs the duration of Salmonella diarrhea by suppressing Bacteroides spp. and reducing vitamin B6 levels in the gut. Controlling the RegIIIβ-dependent effects might be a promising avenue for treating Salmonella-induced diarrhea.


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