The exact mechanism of pathogenesis of inflammatory bowel disease (IBD) is not yet clear. However, a key role for intestinal bacteria in the development and maintenance of IBD is now well-accepted and has led to extensive efforts to characterize IBD patients’ gut microbiota composition. Nonetheless, few studies have examined intestinal microbial composition and host interactions in pediatric treatment-naïve IBD subjects. Using a multi-omic approach, we analyzed the gut microbiota-host interactions at the mucosal- luminal interface from two distinct colonic regions in a pediatric treatment-naïve cohort of Crohn’s disease (CD), ulcerative colitis (UC) and non-IBD control individuals. CD patients displayed a significant decrease in bacterial richness in the distal colon, as compared to controls. Significant changes in the microbial composition at different taxonomic levels were observed in IBD patients relative to controls, especially in the distal colon. IBD patients had an increased abundance of hydrogen sulfide (H2S) producers, including Veillonella (g), Streptococcus (g) and Fusobacterium (g), and a decreased abundance of butyrate producers such as Blautia (g), Lachnospiraceae (f) and Ruminococcus (g). IBD patients showed statistical differences in their metabolomic profile as compared to controls, with the majority of significant metabolites, such as pesticides, amino acids, bacterial-derived molecules and dipeptides, being increased in CD and UC subjects. An alteration of the gut microbiota composition was associated with an alteration of the host and bacteria metabolome in IBD subjects; notably, increase of taurine, mecarbam-f7 and oxazole positively correlated with H2S producers and negatively correlated with butyrate producers. Finally, microbial genes involved in oxidative stress response, virulence, iron uptake, storage and metabolism were upregulated in the proximal colon of IBD patients. Our findings provide information about the host-microbiota interactions in the context of IBD. Understanding the relationships between the host and his intestinal microbes could help to develop therapeutic strategies to treat IBD.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/43502 |
| Date | 21 April 2022 |
| Creators | Schramm, Laetitia |
| Contributors | Stintzi, Alain |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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