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Microbiota in Colorectal Cancer and Other Cancers: Hidden Players in Tumor Biology

For many years, cancer was mainly seen as a disease of our cells: mutations in DNA, uncontrolled growth, and failure of the immune system to eliminate abnormal cells. Today, another actor has entered the scene our microbiota, the trillions of microbes that live in and on our body.

Among all cancers, colorectal cancer (CRC) is one of the best studied in relation to the gut microbiota. But growing evidence suggests that microbes may also influence cancers in other organs, including the liver, pancreas, and even sites far from the intestine.

In this article, we explore how microbiota is linked to colorectal cancer, what is known about other cancers, and why this field is becoming so important for early detection and future therapies.

1. What Do We Mean by “Microbiota in Cancer”?

The gut microbiota is a complex ecosystem of bacteria, archaea, viruses, and fungi that inhabit the digestive tract. In healthy conditions, this ecosystem supports digestion, immune balance, and barrier function.

In cancer, things can change:

  • The composition of the microbiota shifts (dysbiosis).

  • Some bacteria may promote inflammation or produce toxins.

  • Others may protect against tumor development by supporting immune surveillance and maintaining barrier integrity.

2. Microbiota in Colorectal Cancer: What We Know

Colorectal cancer develops in the intestine, exactly where the gut microbiota lives in highest density. This makes CRC a natural focus for microbiome research.

2.1. Dysbiosis in Colorectal Cancer

Many studies have shown that people with colorectal cancer have a different gut microbiota profile than healthy individuals. Common trends include:

  • Enrichment of potentially pro-carcinogenic bacteria

  • Decrease in some beneficial commensal species

  • Overall signs of dysbiosis and altered microbial diversity

Certain bacterial species frequently appear in CRC-associated microbiota, such as Fusobacterium nucleatum and some strains of Escherichia coli and Bacteroides fragilis with specific virulence factors.

2.2. How Can Bacteria Promote Colorectal Cancer?

Microbes may influence colorectal carcinogenesis through several mechanisms:

a) Chronic Inflammation

Some bacteria stimulate persistent low-grade inflammation in the intestinal mucosa. Chronic inflammation leads to:

  • Increased production of reactive oxygen and nitrogen species

  • Repeated tissue damage and regeneration

  • A microenvironment that favors DNA damage and tumor growth

Inflammatory bowel disease (IBD), which involves chronic gut inflammation and microbiota changes, is a known risk factor for CRC.

b) Production of Genotoxins and Carcinogenic Metabolites

Certain bacteria can produce toxins or metabolites that damage DNA or interfere with cell cycle control. Examples (conceptually):

  • Bacterial toxins that directly affect DNA integrity

  • Metabolites that interfere with normal cell signaling or promote cell proliferation

Over time, these effects may contribute to the accumulation of mutations and malignant transformation of epithelial cells.

c) Disruption of Barrier Integrity

Dysbiosis can impair the intestinal barrier, making it more permeable. This allows microbial products to cross into deeper tissues, triggering immune activation and potentially altering the local environment around emerging tumors.

d) Modulation of the Immune System

The microbiota shapes local and systemic immunity. Some bacteria may:

  • Suppress effective anti-tumor immune responses,

  • Or, conversely, stimulate an immune environment that helps tumors escape detection.

Together, these mechanisms contribute to a microenvironment favorable to tumor initiation, promotion, and progression.

3. Microbiota and the Tumor Microenvironment

Tumors are not just masses of cancer cells. They are complex ecosystems that include:

  • Immune cells

  • Fibroblasts and stromal cells

  • Blood vessels

  • Extracellular matrix

  • And, in the case of colorectal tumors, bacteria living within or near the tumor tissue

Studies have detected bacterial DNA and live bacteria inside colorectal tumors. Some microbes appear to:

  • Cluster specifically in tumor tissue compared to adjacent normal mucosa

  • Interact with tumor cells and immune cells

  • Potentially influence tumor growth and response to treatment

This idea of a “tumor-associated microbiota” is reshaping how we see cancer biology.

4. Beyond the Colon: Microbiota and Other Cancers

Although colorectal cancer is the best-characterized example, microbiota may also be linked to cancers in other organs.

4.1. Liver Cancer

The intestine and liver are connected through the portal circulation. Microbial components and metabolites produced in the gut can reach the liver directly. Dysbiosis and increased intestinal permeability may:

  • Deliver pro-inflammatory microbial products to the liver

  • Contribute to chronic liver inflammation, fatty liver disease, and fibrosis

  • Create conditions that favor hepatocellular carcinoma development

Thus, alterations in the gut–liver axis may be part of the story in liver cancer.

4.2. Pancreatic and Biliary Cancers

Some research suggests that microbiota might influence pancreatic cancer and biliary tract cancers through:

  • Migration of oral or intestinal bacteria to the pancreas and biliary tree

  • Modulation of immune responses

  • Interaction with risk factors such as chronic pancreatitis and metabolic alterations

The evidence is still emerging, but it supports a broader view where microbial ecosystems affect organs beyond the gut.

4.3. Distant Organs

There is increasing interest in the possible role of microbiota (gut, oral, or local) in cancers of:

  • The oral cavity and esophagus

  • The breast

  • The lungs, via the gut–lung axis and local respiratory microbiota

In these cases, mechanisms may include systemic inflammation, immune modulation, and circulation of microbe-derived metabolites.

5. Microbiota and Cancer Therapies: Friend or Foe?

Microbiota not only influences cancer risk, but can also affect how patients respond to treatment.

5.1. Response to Chemotherapy and Immunotherapy

Some findings suggest that:

  • Certain microbes can activate or inactivate chemotherapeutic drugs

  • Microbiota composition may impact the efficacy of immune checkpoint inhibitors and other immunotherapies

  • Specific bacterial profiles are associated with better or worse treatment outcomes

This raises the possibility that modulating the microbiota could improve therapeutic response or reduce side effects.

5.2. Antibiotics and Cancer Outcomes

Because antibiotics alter the microbiota, their use may have unintended effects on:

  • Tumor behavior

  • Risk of infection during treatment

  • Response to immunotherapy

This area is complex and highly context-dependent, but it reinforces the idea that microbiota and cancer management are connected.

6. Microbiota as a Biomarker in Cancer

One of the most promising applications is using microbiota as a non-invasive biomarker. For colorectal cancer, this includes:

  • Detecting specific microbial signatures in stool that differ between healthy individuals, adenomas, and CRC

  • Combining microbial markers with existing screening tools to improve early detection

In the future, microbiota-based biomarkers may help:

  • Identify people at increased risk

  • Monitor disease progression or recurrence

  • Predict which patients are more likely to respond to certain therapies

However, real-world application requires:

  • Standardized sampling and analysis methods

  • Validation across different populations

  • Clear clinical guidelines

7. Challenges and Future Perspectives

The field of microbiota and cancer is full of potential, but several challenges remain:

  • Causality vs correlation: Are microbes driving cancer, or simply growing better in a tumor environment? Often, it is a combination of both.

  • Inter-individual variability: Each person’s microbiota is unique and shaped by diet, genetics, lifestyle, and medications.

  • Methodological differences: Different studies use different sampling methods, sequencing platforms, and analysis pipelines.

  • Safety of interventions: Approaches like probiotics, diet changes, or even fecal microbiota transplantation must be carefully evaluated in oncology settings.