Work

Early-life gut dysbiosis programs divergent metabolic trajectories in a sex-dependent manner

Year: 2026

Type: article

Abstract: Previous studies have established that long-term antibiotic (ABX) exposure disrupts gut microbiota, leading to adiposity, insulin resistance, and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the metabolic effects of short-term ABX treatment in early life, along with the underlying mechanism, remain unclear. This study reveals that short-term ABX exposure during early life induces sex-specific metabolic programming in mice. Immature males exhibited reduced gonadal white adipose tissue (gWAT) mass, predisposing them to exacerbated hepatic steatosis under high-fat diet (HFD) challenge. Females displayed protected liver metabolism. We identified dimethylarsinous acid (DMAIII) as a key microbiota-dependent metabolite that inversely correlated with both gWAT mass and specific bacterial abundances, including Muribaculum gordoncarteri and Ligilactobacillus apodemi in male mice. Critically, timely fecal microbiota transplantation (FMT) reversed these metabolic alterations in males. Our findings demonstrate that transient early-life microbiota disruption programs lasting, sex-divergent metabolic outcomes, highlighting the therapeutic potential of microbiota-targeted interventions during developmental windows.

Source: Gut Microbes

DOI: 10.1080/19490976.2026.2718681

Authors: Junlei Su, Yunchong Guo, Lijun Shen, Yaqing Wen, Bihui Huang, Fangping Li

Institutions: Sun Yat-sen University, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen Memorial Hospital

Language: English

Topic: Gut microbiota and health

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,060