Our gut is home to trillions of microbes that help digest food, train the immune system and produce a range of chemical signals.
A new review pulls together evidence showing how these microbes may connect obesity, metabolic problems and colorectal cancer (bowel cancer), and how they might be used to prevent and detect disease.
In the United States, around 40% of adults are living with obesity, which raises the risk of heart disease, type 2 diabetes and several cancers.
Colorectal cancer is the second leading cause of cancer death.
Research is increasingly showing that the gut microbiome:
- Helps regulate metabolism and body weight
- Influences chronic low-grade inflammation and insulin resistance
- Interacts with the immune system in ways that can either protect against or promote cancer
Large cohort studies, such as the Nurses’ Health Study, Health Professionals Follow-Up Study and NHANES, have linked specific microbial patterns to obesity and cancer risk.
How gut microbes may drive risk
Several mechanisms are highlighted:
Energy extraction from food
The microbiome in people with obesity often has a greater capacity to break down otherwise indigestible carbohydrates into absorbable energy.
This can increase the amount of calories pulled from the same amount of food.
Short-chain fatty acids (SCFAs)
Microbes produce SCFAs like butyrate, acetate and propionate when they ferment dietary fibre. These:
- Support the gut barrier
- Help regulate appetite
- Improve insulin sensitivity
However, changes in SCFA production and the balance of species that make them can be linked with fat build-up and a “leaky” gut.
Endotoxaemia and inflammation
When the gut barrier is compromised:
- Gram-negative bacteria and their lipopolysaccharides (LPS) can seep into the bloodstream
- This activates toll-like receptor 4 (TLR4) and other immune pathways
- Chronic low-level inflammation develops in fat tissue and the liver
Over time, this can worsen insulin resistance and contribute to a tumour-friendly environment.
Mutagens and cancer-promoting toxins
Some microbial products are protective, others are harmful:
- Butyrate can promote cancer cell death and support healthy cells
- Certain strains of Escherichia coli produce colibactin, which can damage DNA and promote mutations
So the mix of microbes and their metabolites really matters.
Using the microbiome for diagnosis and treatment
The review highlights several practical applications already emerging:
- Stool-based tests that combine microbial markers such as Fusobacterium nucleatum, colibactin-positive E. coli and toxin-producing Bacteroides fragilis with standard faecal immunochemical tests can improve early detection of colorectal cancer
- Specific probiotic strains, including Bifidobacterium and Lactobacillus, have been shown to improve insulin sensitivity and reduce inflammation in people with obesity or metabolic syndrome
- Prebiotics like inulin and resistant starch encourage butyrate-producing bacteria that may help protect against cancer
Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection and shows how resetting the microbiome can be used therapeutically. Newer approaches are testing engineered probiotics and bacteriophages against cancer-associated microbes.
For now, the most practical advice remains familiar: eat more fibre, fewer ultra-processed foods, move more and avoid smoking.
These behaviours support a healthier microbiome and, by extension, better metabolic and bowel health.
Study: Moseeb MH et al. Oncoscience 2025.
