Granisetron Alleviates Sepsis-Induced Intestinal Injury via Microbiota-Dependent Modulation of the Tryptophan-Quinolinic Acid-AhR Axis.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro study.
PubMed 42609853 · doi:10.2147/JIR.S595022
What was done
Sepsis was induced by intraperitoneal lipopolysaccharide (LPS) injection in conventional and antibiotic-treated (ABX) male C57BL/6 mice, with and without granisetron (GA) intervention. Intestinal tissue damage and inflammation were evaluated using hematoxylin-eosin (HE) staining and ELISA. Multi-omics analyses assessed gut microbiome composition and tryptophan metabolic flux, MetOrigin mapped microbial origins of target metabolites, and the downstream aryl hydrocarbon receptor (AhR) and Wnt/β-catenin pathways were evaluated in vitro.
What was found
The abstract reports no numerical data, effect sizes, or confidence intervals. Directionally, granisetron administration reduced intestinal injury and inflammation in septic mice, remodeled the gut microbiota (identifying *Lactobacillus johnsonii* as a contributor), elevated quinolinic acid (QA) levels, and stimulated AhR and downstream Wnt/β-catenin signaling to support intestinal barrier integrity.
Why it matters
This study outlines a mechanistic gut microbiota-tryptophan metabolite pathway through which granisetron may protect intestinal barrier function during endotoxin-induced inflammation.
Limits
The study is restricted to preclinical animal and in vitro models, limiting generalizability to human clinical sepsis. Sample size was not reported in the abstract. Endotoxin injection does not fully capture the complexity of polymicrobial live-pathogen sepsis, and only male mice were studied.
Cited by
- contradicts Quinolinic acid circulating in the gut contributes to increased gut permeability (leaky gut).