A recent review published in Oncoscience examines the role of the gut microbiome as both a biomarker and therapeutic target in obesity, metabolic syndrome, and colorectal cancer (CRC). The review highlights that metabolic syndrome, obesity, and CRC are prevalent health challenges in the United States. Approximately 40% of U.S. adults are obese, which raises their risk for cardiovascular disease, type 2 diabetes, and cancer.
Colorectal cancer is identified as the second leading cause of cancer death in the U.S., with strong links to dietary and lifestyle factors. Both obesity and CRC contribute significantly to healthcare costs and mortality rates.
The gut microbiome—comprising bacteria, archaea, fungi, and viruses—plays an essential role in metabolism, immunity, and carcinogenesis. Dysbiosis within this system is commonly observed among individuals with obesity or chronic inflammation. Research from studies such as the Nurses’ Health Study and National Health and Nutrition Examination Survey (NHANES) has found associations between specific microbial signatures, CRC risk, and obesity phenotypes.
Metagenomic analyses indicate that obese individuals have a gut microbiome capable of extracting more energy from otherwise indigestible polysaccharides. However, because human microbiomes vary widely based on diet, ethnicity, and geography, further research is needed to identify universal or population-specific patterns related to obesity.
Short-chain fatty acids (SCFAs)—including butyrate, acetate, and propionate—are produced by certain gut microbes. These metabolites can improve gut barrier function, regulate appetite, and influence insulin sensitivity through G-protein-coupled receptors. Changes in SCFA profiles have been linked to increased fat production and impaired barrier integrity.
Dysbiosis also leads to higher levels of Gram-negative pathogenic bacteria that release lipopolysaccharides (LPS), which promote endotoxemia. This triggers toll-like receptor 4 (TLR4) signaling pathways that enhance insulin resistance in tissues such as adipose tissue and liver.
Chronic activation of inflammatory pathways—including LPS/TLRs/flagellin/MAPK/NF-κB—results in proinflammatory cytokine secretion that sustains environments conducive to tumor growth. Butyrate acts as a histone deacetylase inhibitor influencing gene transcription; meanwhile colibactin—a product of some Escherichia coli species—can cause DNA damage leading to mutations.
Multi-omics approaches combining metagenomics with metabolomics or transcriptomics are increasingly used to clarify how microbial pathways affect disease risk. Researchers have begun integrating electronic health records with multi-omics data for improved screening methods.
Environmental factors such as air pollution—as well as diet, smoking habits, sleep patterns, physical activity—affect both the composition of the microbiome and disease mechanisms tied to it. Understanding these influences may help design more effective personalized prevention strategies using insights from microbiome science.
Molecular pathological epidemiology (MPE) combines molecular pathology with epidemiologic analysis to study disease heterogeneity arising from interactions among lifestyle choices, environment, and genetics. MPE has already been used in gastrointestinal cancers including CRC to examine how microbial signatures interact with immune markers or mutational profiles.
Diagnostic tools like stool-based microbiome profiling can detect early-stage CRC by identifying specific bacterial species such as Fusobacterium nucleatum or colibactin-producing E. coli when combined with fecal immunochemical testing (FIT).
Clinical trials have shown improvements in insulin sensitivity among people taking probiotics containing Bifidobacterium or Lactobacillus strains; prebiotics like inulin promote beneficial bacteria that produce anticarcinogenic butyrate. Fecal microbiota transplantation (FMT) can restore healthy microbial balance; notably RBX2660 (Rebyota) became the first FDA-approved therapy for preventing recurrent Clostridium difficile infection using this approach.
Researchers are evaluating engineered probiotics for use against oncology or metabolic disorders while bacteriophage therapy targeting harmful taxa such as Fusobacterium nucleatum is under preclinical investigation.
Despite these advances additional research is necessary before translating microbiota-based therapies into routine clinical practice due largely to a lack of standardized methodologies across studies—a challenge addressed by initiatives like the National Microbiome Data Collaborative aimed at harmonizing data standards for broader clinical adoption.
Future efforts will require large-scale longitudinal studies incorporating dietary lifestyle data alongside microbiome analyses for better understanding causality over time; advanced AI models could integrate genomic metabolomic information for enhanced prediction of disease risk across diverse populations.
