Background: Accumulating evidence suggests that consumption of wheat arabinoxylan (WAX) has many beneficial effects to the host, such as strengthening the immune system and lowering inflammatory disease risk. WAX is a source of prebiotic that can be metabolized by the gut bacteria into various bioactive metabolites. However, how WAX-derived bacterial metabolites protect the host from inflammation remains incompletely understood. In this study, we aim to investigate whether a human commensal Bacteroides intestinalis, a known WAX fermenter in vitro, can metabolize WAX in vivo into various bioactive metabolites to benefit host health. We aim to identify anti-inflammatory WAX-derived B. intestinalis metabolites and characterize how their anti-inflammatory activities can benefit the host.
Method: To characterize how WAX-derived B. intestinalis metabolites can mitigate inflammation, germ-free C57BL6/J mice were monoassociated with B. intestinalis and fed with either isocaloric negative control diet or WAX-supplemented diet. Then, mice were supplied with drinking water containing DSS to induce colitis. We assessed inflammation by performing histological and molecular analyses for colon and lymphoid tissues. To identify all WAX-derived B. intestinalis metabolites absorbed by the host, we performed untargeted metabolomics analysis on mouse serum samples. To elucidate how the metabolites mitigate inflammation, we are testing their effects on the host immune system in vivo using the zebrafish as a model due to its optical transparency and ease of neutrophil visualization, tracking, and quantification in real time.
Preliminary results: We found that the colitis symptoms were significantly attenuated in mice fed with WAX-supplemented diet, suggesting WAX-derived B. intestinalis metabolites mitigated DSS-induced inflammation. Moreover, we found a significant increase in the serum bioavailability of WAX-derived hydroxycinnamic acids, which have been reported to have anti-inflammatory activity. Among the most abundant hydroxycinnamic acids absorbed by the host, we identified ferulic acid, a known antioxidant molecule, as a candidate anti-inflammatory WAX-derived B. intestinalis metabolite.
Significance: By identifying which B. intestinalis metabolite(s) exerts beneficial effects on host health, we will build a knowledge base for how WAX can benefit host health via Bacteroides intestinalis metabolism. With this knowledge, it will be possible to create a personalized diet to precisely manipulate the gut microbiome and its metabolites to mitigate inflammatory diseases.

Ziyu Zhou

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