Inflammatory potential of gut microbiota from monozygotic twin pair discordant for ulcerative colitis

Abstract

Gut microbiota perturbations are common in inflammatory bowel disease (IBD), including ulcerative colitis (UC), but it is unclear whether this is a result of the disease or a contributing factor. In twin pairs discordant for IBD, the healthy co-twin is at an increased risk of IBD and has a gut microbiota more similar to IBD patients than healthy individuals. Moreover, appropriate medical treatment may reduce the perturbations. To investigate the association of the microbiota and IBD, we transferred stool from a discordant twin pair, i.e. one healthy and one treated for UC, to germ-free mice by the inoculation of pregnant dams. Dextran sodium sulfate was used to induce colitis in the pups. Offspring of mice inoculated with stool from the UC twin had a lower disease activity index (DAI) and gut inflammation and microbiota with higher alpha diversity and a more anti-inflammatory profile, with the exclusive presence of the anti-inflammatory Akkermansia species, compared to offspring of mice inoculated with stool from the healthy co-twin. These results indicate that the healthy twin had a more inflammatory microbiota than the twin treated for UC. Our study suggests that individuals genetically susceptible to IBD have a more inflammatory gut microbiota. Future studies should assess the potential use of individual gut microbiota inflammatory profiles in personalised medicine.