Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota

Abstract

Background The aetiology and pathogenesis of IBD are intricate, involving genetic and environmental factors. Notably, cigarette smoking has contrasting effects, being detrimental to Crohn’s disease (CD) and beneficial to UC. However, the mechanisms underlying these opposite effects remain unclear. Objective This study aimed to elucidate the precise mechanisms by which smoking influences IBD pathogenesis, by focusing on the roles of microbiota and metabolomics. Design We analysed the microbiota composition of saliva, faeces and the colonic mucosa, and the faecal metabolite profile of patients with IBD and healthy participants. The effects of smoking-associated bacteria on the gut immune system and colitis were evaluated using gnotobiotic mice and murine models of UC and CD. Results People with UC who smoke showed increased concentrations of short-chain fatty acids and aromatic compounds in the faeces compared with the people who quit smoking. The analysis of the mucosal microbiota revealed that smoking is associated with the increased oral bacteria in the colonic mucosa. Monocolonisation of germ-free mice with Streptococcus mitis , one of the oral bacteria ectopically increased in the colonic mucosa, induced interferon (IFN)-γ-producing T cells in the colon. S. mitis also attenuated inflammation in a murine model of UC but exacerbated it in a CD model. Conclusion We demonstrated that smoking affects the gut immune system by modulating mucosal microbiota. Our findings provide insights into how smoking can have beneficial or detrimental effects on UC or CD, respectively, and may shed light on the reasons why individuals with UC who quit smoking experience disease exacerbation. Data are available in a public, open access repository. The 16S rRNA sequence data and the genome sequence data of Streptococcus rubneriS. mitis have been deposited in the DDBJ under BioProject accession numbers PRJDB35832 and PRJDB35831, respectively.