Dietary choline deficiency potentiates Helicobacter pylori-driven gut-liver dysfunction via microbial metabolic rewiring

Abstract

Background & aims: Approximately half of the global population is infected with Helicobacter pylori (H. pylori), yet the severity of clinical manifestations post-infection exhibits substantial heterogeneity, a disparity strongly correlated with host dietary and nutritional status. Choline deficiency, a widespread but frequently neglected condition, demonstrates poorly characterized mechanistic connections with H. pylori-induced pathological damage.

Methods: C57BL/6 J mice were subjected to choline-deficient diet (CDD) and H. pylori infection for 8- and 16-week intervals to model the association between choline deficiency and H. pylori-induced pathogenesis. Glucose-lipid metabolism, inflammatory responses, and tissue injury markers were assessed in mice. The expression of gastrointestinal barrier-related proteins was analyzed, and histopathological evaluations were conducted across gastric, intestinal, and hepatic tissue specimens. High-throughput targeted metabolomics and 16S rRNA sequencing were applied to evaluate choline metabolism.

Results: H. pylori disrupts microbial-host choline metabolism, characterized by accelerated gut microbial trimethylamine (TMA) biosynthesis coupled with impaired host flavin-containing monooxygenase 3 (FMO3) activity, ultimately driving dysregulated production of trimethylamine N-oxide (TMAO). Concurrently, CDD establishes a vulnerable gut microbial architecture predisposed to H. pylori-induced disruption, with their synergistic interaction driving the emergence of dominant choline-metabolizing microbiota. Ultimately, the synergistic interaction between CDD and H. pylori leads to more severe elevation of inflammation and injury markers.

Conclusions: CDD amplified H. pylori-induced disruption of choline metabolism via gut microbiota remodeling, thereby exacerbating gut-liver axis dysfunction. This study suggests that H. pylori-infected individuals require attention to maintaining dietary balance to prevent choline deficiency.

Keywords: Choline deficiency; Gut microbiota; Gut-liver axis; Helicobacter pylori; Lactobacillus; Trimethylamine N-oxide.