Journal Article

Precision editing of the gut microbiota ameliorates colitis

Koh, Andrew Y., Winter, Maria G., Hughes, Elizabeth R., Lopez, Christopher A., Wilson, R. Paul, Gillis, Caroline C., Zhu, Wenhan, Duerkop, Breck A., Winter, Sebastian E., Hooper, Lora V., Bäumler, Andreas J., de Lima Romão, Everton, Tükel, Çagla, Büttner, Lisa, Spiga, Luisella, Burstein, Ezra, Sifuentes-Dominguez, Luis, Behrendt, Cassie L., Huff-Hardy, Kayci, Byndloss, Mariana X.

2018

Overview

Tungstate inhibits molybdenum-cofactor-dependent microbial respiratory pathways and shows potential as a selective treatment for microbial imbalances that occur during inflammation of the gastrointestinal tract. Countering colon inflammation Expansion of facultative anaerobic bacteria of the Enterobacteriaceae family in the gut is associated with dysbiosis—an imbalance in the microbiota—and inflammatory bowel disease. Sebastian Winter and colleagues show that tungstate treatment, which selectively inhibits molybdenum-cofactor-dependent microbial respiratory pathways that operate only during episodes of inflammation, mitigates inflammation in mouse models of colitis without causing any compositional alterations to the gut microbiota. This is a promising strategy for precision therapy of the microbiota in response to inflammatory disorders, but future work is needed to determine whether similar approaches could be relevant in humans. Inflammatory diseases of the gastrointestinal tract are frequently associated with dysbiosis 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , characterized by changes in gut microbial communities that include an expansion of facultative anaerobic bacteria of the Enterobacteriaceae family (phylum Proteobacteria). Here we show that a dysbiotic expansion of Enterobacteriaceae during gut inflammation could be prevented by tungstate treatment, which selectively inhibited molybdenum-cofactor-dependent microbial respiratory pathways that are operational only during episodes of inflammation. By contrast, we found that tungstate treatment caused minimal changes in the microbiota composition under homeostatic conditions. Notably, tungstate-mediated microbiota editing reduced the severity of intestinal inflammation in mouse models of colitis. We conclude that precision editing of the microbiota composition by tungstate treatment ameliorates the adverse effects of dysbiosis in the inflamed gut.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 45/23 / 631/250/256/2516 / 631/326/2565/2134 / 64/60 / 96/21 / Anaerobic bacteria / Anaerobic microorganisms / Anaerobiosis - drug effects / Animal models / Animals / Bacteria / Bacteroides / Binding sites / Cell Respiration - drug effects / Colitis / Colitis - drug therapy / Colitis - microbiology / Digestive system / Dysbacteriosis / Dysbiosis - drug therapy / Dysbiosis - microbiology / E coli / Enterobacter cloacae / Enterobacteriaceae / Enterobacteriaceae - drug effects / Enterobacteriaceae - growth & development / Enterobacteriaceae - metabolism / Enzymes / Escherichia coli / Female / Gastrointestinal Microbiome - drug effects / Gastrointestinal tract / Gene expression / Genetic engineering / Gut microbiota / Health aspects / Humanities and Social Sciences / Inflammation / Inflammation - drug therapy / Inflammation - microbiology / Inflammation - pathology / Inflammatory bowel disease / Inflammatory diseases / Intestinal microflora / Intestinal Mucosa - drug effects / Intestinal Mucosa - microbiology / Intestinal Mucosa - pathology / Intestine / Intestines - drug effects / Intestines - microbiology / Intestines - pathology / letter / Male / Metabolism / Mice / Mice, Inbred C57BL / Microbial activity / Microbiota / Microbiota (Symbiotic organisms) / Microorganisms / Molybdenum / Molybdenum - metabolism / multidisciplinary / Oxidation / Physiological aspects / Salmonella / Salmonella enterica / Science / Tungsten Compounds - pharmacology / Tungsten Compounds - therapeutic use