Early-life Helicobacter pylori infection in mice alters endocrine signaling and accelerates adipose expansion during high-fat feeding

Abstract

Perturbations to early-life microbial colonization can shape immune and metabolic development, predisposing a host to obesity. We hypothesized that neonatal infection with the ancient human symbiont Helicobacter pylori exacerbates diet-induced metabolic responses and is accompanied by alterations in endocrine and inflammatory regulation. To test this, C57BL/6JRj neonatal mice were infected with H. pylori or left uninfected and, after weaning, exposed to a high-fat diet in a long-term (5-month) study of microbiome composition and a short-term (3-week) study of circulating biomarkers and microbiome composition. In the short-term intervention, infected mice showed increased visceral adiposity. Infection was associated with altered ghrelin and leptin responses across fasting conditions, accompanied by elevated MCP-1 and IL-6, particularly in males. H. pylori infection also reinforced diet-induced shifts in gastrointestinal microbiome composition. In the long-term study, there were no differences in adiposity between infected and control mice, suggesting that diet was the dominant determinant of adiposity at this stage. Together, our findings suggest that early-life H. pylori infection amplifies the initial endocrine, inflammatory, and adipose responses to a high-fat diet.