Impact of Mild COVID-19 History on Oral-Gut Microbiota and Serum Metabolomics in Adult Patients with Crohn’s Disease: Potential Beneficial Effects

The impact of coronavirus disease 2019 (COVID-19) history on Crohn's disease (CD) is unknown. This investigation aimed to examine the effect of COVID-19 history on the disease course, oral-gut microbiota, and serum metabolomics in patients with CD. In this study, oral-gut microbiota and serum metabolomic profiles in 30 patients with CD and a history of mild COVID-19 (positive group, PG), 30 patients with CD without COVID-19 history (negative group, NG), and 60 healthy controls (HC) were assessed using 16S rDNA sequencing and targeted metabolomics. During follow-up, the CD activity index showed a stronger decrease in the PG than in the NG (<i>p</i> = 0.0496). PG patients demonstrated higher α-diversity and distinct β-diversity clustering in both salivary and fecal microbiota compared to NG and HC individuals. Notably, the gut microbiota composition in the PG patients showed a significantly greater similarity to that of HC than NG individuals. The interaction between oral and intestinal microbiota in the PG was reduced. Moreover, serum metabolome analysis revealed significantly increased anti-inflammatory metabolites, including short-chain fatty acids and N-Acetylserotonin, among PG patients; meanwhile, inflammation-related metabolites such as arachidonic acid were significantly reduced in this group. Our data suggest that the gut microbiota mediates a potential beneficial effect of a mild COVID-19 history in CD patients.