<b>Role of microbial dysbiosis on the anti-colitic activity of 3-deoxyflavonoids and 3-hydroxyflavonoids</b>

<p dir="ltr">Gut microbiota dysbiosis is a hallmark of inflammatory disorders such as ulcerative colitis (UC). Flavonoids, recognized for their anti-inflammatory and microbiota-modulatory properties, offer a safer alternative to conventional drugs. While gut microbiota play a critical role in flavonoid efficacy, most studies rely on murine-native microbiota, limiting insights into interactions with human-associated microbiota. This dissertation addresses this gap by investigating how human microbiota influence the anti-colitic effects of 3-deoxyflavonoids (3-DF) and 3-hydroxyflavonoids (3-HF).</p><p dir="ltr">In the first study, germ-free IL-10−/− mice were colonized with microbiota from healthy human donors and supplemented with diets enriched in 3-DF, 3-HF, or both. While pooling the data from different donors for each diet showed no significant effects on inflammatory markers or microbial diversity. Anthocyanin-containing diets (3-HF) improved gut barrier function. Importantly, 3-HF effects varied by donor microbiota, with significant benefits in specific recipients.</p><p dir="ltr">The second study used UC-associated microbiota to colonize mice. Flavonoids either ameliorated or aggravated colitis symptoms depending on the microbiota composition. Improvements in gut barrier function and inflammation positively correlated with short-chain fatty acid and bile acid levels.</p><p dir="ltr">In the third study, fecal supernatants (FS) were evaluated <i>in vitro</i>. FS from healthy microbiota attenuated NF-κB activation and maintained barrier integrity, while FS from UC-associated microbiota exacerbated inflammation and permeability. Temporal analysis revealed constrained modulation of dysbiotic microbiota compared to healthy microbiota.</p><p dir="ltr">These findings underscore the pivotal role of microbiota composition and health status in flavonoid activity. They lay the foundation for personalized dietary interventions targeting inflammation based on individual microbiota profiles.</p>