Doctoral Dissertation Defense - Meifan Zhang

Microbial Biology Graduate Program

Doctoral Dissertation Defense

Meifan Zhang

"Systemic Effects of Early-Life, Low-Dose Penicillin on Metabolic Organs to Promote Adiposity in a Mouse Model"

Committee Members: Dr Martin Blaser (Advisor), Dr. Judith Storch, Dr. Christoph Buettner, Dr. Xiaoyang Su

Zoom Details for Dissertation Defense

Please email Lindsay Vasy for information (lindsay.vasy@rutgers.edu).

Dissertation Summary

Although obesity is a global epidemic, its pathogenesis remains largely obscure. Previous experimental models using low-dose antibiotics, a historical agricultural growth-promotion strategy, have linked early-life exposure to later-life obesity. Grounded in the Developmental Origins of Health and Disease (DOHaD) framework, this dissertation investigates how antibiotic-induced microbiome disruptions during critical developmental windows alter metabolism, predisposing young mice to adult obesity.

Focusing on adipose tissue and the liver, we exposed murine pups to low-dose penicillin (LDP) from birth for 1, 2, or 4 weeks, followed by dietary or environmental stressors. LDP exposure accelerated early gains in body weight and fat mass, effects synergistically exacerbated by a high-fat diet. Remarkably, by postnatal day 7, LDP-treated mice had increased hepatic and adipose mass that persisted through weaning, accompanied by disturbances in the growth hormone (GH) and insulin-like growth factor 1 (IGF-1) somatotrophic axis. Ligilactobacillus was identified as a key protective bacterial taxon. Ultimately, these data demonstrate that microbiome perturbations during a critical early-life window alter metabolic organs and endocrine regulatory systems, driving accelerated growth and the pathogenesis of obesity.