Microbial Dynamics in Newly Diagnosed and Treatment Naïve IBD Patients in the Mediterranean.

BACKGROUND: Microbial communities have long been suspected to influence inflammatory processes in the gastrointestinal tract of patients with inflammatory bowel disease. However, these effects are often influenced by treatments and can rarely be analyzed in treatment-naïve onset cases. Specifically, microbial differences between IBD pathologies in new onset cases have rarely been investigated and can provide novel insight into the dynamics of the microbiota in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Fifty-six treatment-naïve IBD onset patients (67.3% CD, 32.7% UC) and 97 healthy controls were recruited from the Maltese population. Stool samples were collected after diagnosis but before administration of anti-inflammatory treatments. Fecal microbial communities were assessed via 16S rRNA gene sequencing and subjected to ecological analyses to determine disease-specific differences between pathologies and disease subtypes or to predict future treatment options. RESULTS: We identified significant differences in community composition, variability, and diversity between healthy and diseased individuals-but only small to no differences between the newly diagnosed, treatment-naïve UC and CD cohorts. Network analyses revealed massive turnover of bacterial interactions between healthy and diseased communities, as well as between CD and UC communities, as signs of disease-specific changes of community dynamics. Furthermore, we identified taxa and community characteristics serving as predictors for prospective treatments. CONCLUSION: Untreated and newly diagnosed IBD shows clear differences from healthy microbial communities and an elevated level of disturbance, but only the network perspective revealed differences between pathologies. Furthermore, future IBD treatment is to some extent predictable by microbial community characteristics.

Treatment-naïve IBD onset patients from Malta show clear differences from healthy microbial communities and an elevated level of community disturbance, although differences between pathologies are only revealed by a network perspective. Furthermore, future IBD treatment is predictable by microbial community characteristics.

Dysbiosis in the Gut Microbiota in Patients with Inflammatory Bowel Disease during Remission.

Inflammatory bowel disease (IBD) is a chronic, relapsing, inflammatory disorder which comprises two main conditions: Crohn's disease (CD) and ulcerative colitis (UC). Although the etiology of IBD has not been fully elucidated, the gut microbiota is hypothesized to play a vital role in its development. The aim of this cross-sectional study was to characterize the fecal microbiota in CD or UC patients in a state of remission to reveal potential factors sustaining residual levels of inflammation and triggering disease relapses. Ninety-eight IBD patients in a state of clinical remission (66 UC, 32 CD) and 97 controls were recruited, and stool samples, as well as detailed patient data, were collected. After DNA extraction, the variable regions V1 and V2 of the 16S rRNA gene were amplified and sequenced. Patients with IBD had a decrease in alpha diversity compared to that of healthy controls, and the beta diversity indices showed dissimilarity between the cohorts. Healthy controls were associated with the beneficial organisms unclassified Akkermansia species (Akkermansia uncl.), Oscillibacter uncl., and Coprococcus uncl., while flavonoid-degrading bacteria were associated with IBD. Network analysis identified highly central and influential disease markers and a strongly correlated network module of Enterobacteriaceae which was associated with IBD and could act as drivers for residual inflammatory processes sustaining and triggering IBD, even in a state of low disease activity. The microbiota in IBD patients is significantly different from that of healthy controls, even in a state of remission, which implicates the microbiota as an important driver of chronicity in IBD. IMPORTANCE Dysbiosis in inflammatory bowel disease (IBD) has been implicated as a causal or contributory factor to the pathogenesis of the disease. This study, done on patients in remission while accounting for various confounding factors, shows significant community differences and altered community dynamics, even after acute inflammation has subsided. A cluster of Enterobacteriaceae was linked with Crohn's disease, suggesting that this cluster, which contains members known to disrupt colonization resistance and form biofilms, persists during quiescence and can lead to chronic inflammation. Flavonoid-degrading bacteria were also associated with IBD, raising the possibility that modification of dietary flavonoids might induce and maintain remission in IBD.