Helicobacter pylori infection promotes TMAO accumulation through Escherichia coli enrichment with gut–liver circadian disruption and hepatic metabolic injury

ABSTRACT: Helicobacter pylori (H. pylori) infection is associated with metabolic dysfunction-associated steatotic liver disease, but the microbial changes and circadian disturbances accompanying distal hepatic injury remain unclear. In specific pathogen-free (SPF) mice exposed to dietary choline, H. pylori infection was accompanied by trimethylamine N-oxide (TMAO) accumulation, ileal barrier disruption, and liver injury. 16S rRNA gene sequencing identified H. pylori-associated intestinal Escherichia enrichment, further supported by increased fecal Escherichia coli (E. coli) 16S rRNA levels and higher E. coli viable counts in medium supplemented with H. pylori culture supernatant. In germ-free–derived gnotobiotic mice, the H. pylori–E. coli co-colonized group had the highest trimethylamine (TMA) and TMAO levels and the most severe gut–liver phenotype. Transcriptomic analyses further identified circadian-pathway alterations in both the ileum and liver. In the liver, high TMAO was associated with reduced rhythmic CLOCK:BMAL1 target-gene output, lower Dbp expression, higher Nfil3 expression, and reduced Ppara expression and PPARα abundance; these changes were not fully explained by a uniform phase shift. In synchronized HepG2 cells, TMAO reproduced the DBP–NFIL3 imbalance and PPARα reduction, whereas DBP overexpression partially restored PPARα and selected metabolic and injury-related readouts. Together, these findings identify intestinal E. coli enrichment as a key contributor to H. pylori-related TMAO accumulation and show that the resulting high-TMAO state involves altered gut–liver circadian regulation and hepatic metabolic injury.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - positive - amide-hilic, Liquid Chromatography MS - negative - c18-reverse-phase-chromatography, Liquid Chromatography MS - positive - reverse-phase-chromatography, Liquid Chromatography MS - positive - c18-reverse-phase-chromatography, Liquid Chromatography MS - positive - reversed-phase-liquid-chromatography, Liquid Chromatography MS - negative - reversed-phase-liquid-chromatography, Liquid Chromatography MS - positive - hydrophilic-interaction-liquid-chromatograph

PROVIDER: MTBLS15673 | MetaboLights | 2026-09-18

REPOSITORIES: MetaboLights