From obesity to cancer: Gut microbiome mechanisms, biomarkers, and U.S. public health strategies.

Abstract

Background: Obesity, metabolic syndrome, and colorectal cancer (CRC) remain major public health challenges in the United States, collectively driving substantial morbidity, mortality, and economic burden. Beyond diet and genetics, the gut microbiome has emerged as a pivotal determinant of host metabolism, immunity, and carcinogenesis, influenced by both environmental and behavioral factors.

Objective: This review synthesizes current evidence linking gut microbial dysbiosis to obesity, metabolic syndrome, and CRC, emphasizing mechanistic pathways, environmental modifiers, and translational opportunities relevant to U.S. public health and precision medicine.

Methods: Comprehensive searches of PubMed and Scopus (2000-2025) identified large epidemiologic studies, mechanistic experiments, and clinical trials, prioritizing research from U.S. populations and nationally representative databases including NHANES, SEER, and the Nurses' Health Study.

Results: Microbial alterations such as enrichment of Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli contribute to CRC initiation and progression. In obesity and metabolic syndrome, shifts in Firmicutes-to-Bacteroidetes ratios, altered short-chain fatty acid metabolism, and endotoxin-mediated inflammation disrupt metabolic homeostasis. Environmental and lifestyle exposures, including air pollutants, smoking, and Westernized diets, modulate microbial ecology across the aerodigestive tract, affecting disease susceptibility. The emerging discipline of Molecular Pathological Epidemiology (MPE) integrates lifestyle, microbiome, and biomarker data to elucidate exposure-outcome relationships, enabling personalized prevention and therapeutic strategies.

Conclusions: The gut microbiome functions as both a biomarker and therapeutic target across metabolic and neoplastic diseases. Integrating microbiome science with environmental epidemiology and MPE frameworks offers transformative potential for precision prevention and equitable public health strategies in the U.S.