Microbiome-driven alterations in tryptophan metabolism contribute to behavioral comorbidities in the Muc2 knockout mouse model of chronic colitis - PubMed
5 hours ago
- #Gut-Brain Axis
- #Behavioral Comorbidities
- #Tryptophan Metabolism
- Chronic colitis in Muc2 knockout mice leads to neurobehavioral issues like reduced anxiety in females and memory problems in males.
- Microbiome alterations cause decreased tryptophan, kynurenine, and serotonin in the gut, affecting brain function.
- Germ-free conditions normalize gut metabolites and eliminate behavioral changes, highlighting microbiome's key role.
- Blood-brain barrier integrity is compromised in Muc2 knockout mice, with reduced claudin-5 expression.
- Microbiome shifts towards indole production and NAD+ salvage, with lower Anaerotruncus, Enterocloster, and Intestinimonas.
- Early-life nutrient supplementation partially restores colonic tryptophan but fails to fully rescue behavior, suggesting complex interactions.