DSS-induced acute colitis causes dysregulated tryptophan metabolism in brain: an involvement of gut microbiota

Feb 9, 2023The Journal of nutritional biochemistry

Gut inflammation causes abnormal tryptophan processing in the brain linked to gut bacteria

AI simplified

Gut-Brain Axis on OpenScience ↗PubMed ↗DOI ↗

Abstract

Acute colitis induced by 3% Dextran sulphate sodium (DSS) leads to significant alterations in tryptophan metabolism in both serum and brain.

More severe intestinal symptoms were observed in acute colitis compared to sub-chronic colitis.
Both colitis types affected the tryptophan-kynurenine pathway in serum by regulating key enzymes.
Only the acute colitis group activated the tryptophan-kynurenine pathway in the brain.
Significant changes in intestinal flora were detected in both DSS-induced colitis groups, affecting microbial diversity and abundance related to tryptophan metabolism.
Elevated functional pathways of microbiomes related to inflammation and tryptophan biosynthesis were noted after DSS treatment.
A significant association exists between intestinal flora and tryptophan metabolism in serum and brain.

AI simplified

Inflammatory bowel disease can cause pathological changes of certain organs, including the gut and brain. As the major degradation route of tryptophan (Trp), Kynurenine (Kyn) pathway are involved in multiple pathologies of brain. This study sought to explore the effects of Dextran sulphate sodium (DSS)-induced colitis on serum and brain Trp metabolism (especially the Kyn pathway) and its mechanisms. We induced acute colitis and sub-chronic colitis with 3% DSS and 1% DSS respectively and found more severe intestinal symptoms in acute colitis than sub-chronic colitis. Both of the colitis groups altered Trp-Kyn-Kynurenic acid (Kyna) pathway in serum by regulating the expression of rate-limiting enzyme (IDO-1, KAT2). Interestingly, only 3% DSS group activated Trp-Kyn pathway under the action of metabolic enzymes (IDO-1, TDO-2 and KAT2) in brain. Furthermore, intestinal flora 16S rRNA sequencing showed significantly changes in both DSS-induced colitis groups, including microbial diversity, indicator species, and the abundance of intestinal microflora related to Trp metabolism. The functional pathways of microbiomes involved in inflammation and Trp biosynthesis were elevated after DSS treatment. Moreover, correlation analysis showed a significant association between intestinal flora and Trp metabolism (both in serum and brain). In conclusion, our study suggests that DSS-induced acute colitis causes dysregulation of Trp-Kyn-Kyna pathways of Trp metabolism in serum and brain by affecting rate-limiting enzymes and intestinal flora.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

DSS-induced acute colitis causes dysregulated tryptophan metabolism in brain: an involvement of gut microbiota

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief