How Does the Microbiome Affect the Success of Cancer Treatment?

Key Facts About the Microbiome

• The microbiome is an ecosystem encompassing the combined genetic material of the microorganisms living in the human body and the interactions among those microorganisms. Microbiota , by contrast, refers to the microorganisms themselves—the bacteria, viruses, fungi, and other microscopic organisms living in our bodies. Throughout the rest of this article, we use the term microbiome to encompass both concepts.
• The human microbiome contains more than 10 thousand different microbial species , which form different ecosystems in different parts of the body.
• The average human body contains approximately 10 trillion cells and harbors 10 times as many microorganisms, approximately 100 trillion microorganisms in total.
• The ratio of bacterial to human cells is estimated at approximately 1.3:1, and viruses and phages are estimated to outnumber bacteria by at least an order of magnitude.
• However, because microorganisms are much smaller, they account for 1-3% of human body weight.
• Most of our body's microbiome is found in the gut and on our skin.

When the gut microbiome becomes imbalanced, a condition called gut dysbiosis occurs. This may be a potential risk factor for various local and systemic diseases.

Cancers and their treatments can also be affected by an imbalanced gut microbiome. Microbiome diversity may influence processes such as tumor growth, inflammation, immune evasion, genomic instability, and the development of treatment resistance.

Microbial diversity may help cancer treatment, as each individual's microbiome composition differs considerably and can change. These features make the gut microbiome an important target in precision microbiotics, with the potential to serve as a biomarker that predicts bodily responses and helps develop personalized diets.

The Microbiome and Its Effects on Disease

The body's microbiome forms a protective barrier in areas exposed to external influences, including the skin, mouth, digestive tract, and urogenital system.

Research in humans and mouse cancer models has shown that certain microorganisms can have positive or negative effects on cancer development and treatment.

Is the Microbiome a Master Regulator?

Disruptions in the gut microbial system during antibiotic treatment can significantly affect a patient's immunotherapy response . Immune checkpoint inhibitor (ICI) treatment outcomes can be affected by antibiotics taken immediately before or after treatment begins: a recently published review and meta-analysis, for example, reported significant effects on both overall and progression-free survival.

Proton pump inhibitors, commonly known as stomach-protecting medicines, also affect the gut microbiome and reduce response to immunotherapy. This effect was demonstrated in an analysis presented at the European Society for Medical Oncology (ESMO) Annual Meeting 2023 using data from more than 2700 cancer patients.

The extent to which the gut microbiome affects or predicts immunotherapy efficacy was demonstrated in a retrospective analysis published in 2018 in Science. Immunotherapy resistance was associated with a low abundance of the bacterium Akkermansia muciniphila in cancer patients' guts. In mouse models, researchers restored immunotherapy efficacy through fecal transplantation.

Predicting Immunotherapy Response

Research by Dr. Laurence Zitvogel and her team examined whether the presence or absence of the bacterium Akkermansia muciniphila (Akk) in the gut could predict immunotherapy efficacy. In a study of patients with non–small-cell lung cancer (NSCLC), those with high fecal Akk levels responded better to immunotherapy and lived longer. This suggests that Akk abundance may be an independent factor in predicting immunotherapy response.

In the first-line setting, patients with high Akk levels had longer median overall survival than those with low levels: 13.4 versus 18.8 months. This may be an important step toward personalizing immunotherapy, as the findings suggest that the composition of the gut microbiome and its metabolites may determine treatment response.

Therapeutic Interventions

Fecal microbiota transplantation (FMT) is a treatment that may help rebuild the gut microbiome. In a phase 1 study led by Dr. Hendrik Poeck, who has experience in cancer treatment, FMT produced positive results in 20 previously untreated patients with advanced melanoma.

Patients began immunotherapy after FMT, and by 12 weeks most had achieved complete or partial remission.

However, FMT also carries potential risks. For example, sepsis (a severe infection) caused by multidrug-resistant Escherichia coli was previously reported in two patients. To reduce these risks, the FDA required more extensive screening of donor stool.

Clinicaltrials.gov lists 46 clinical studies investigating FMT's role in cancer treatment.

Dietary Interventions

Dr. Poeck advises caution with over-the-counter probiotics because they generally contain a limited number of bacterial species and may delay restoration of the microbiome's natural balance after antibiotic treatment.

Probiotic use has also been observed to reduce treatment response or produce mixed results in some cases.

On the other hand, Dr. Poeck explains that prebiotics —fiber-rich foods containing nondigestible carbohydrates—are converted during digestion into short-chain fatty acids that support healthy microbiota. Such a diet has shown positive effects on immunotherapy response, particularly in patients who do not use probiotics and consume enough fiber.

These findings suggest that a prebiotic-rich diet may prolong disease-free survival in patients receiving immunotherapy.

Below is a mind-map diagram summarizing the article:

What Should Be Recommended?

In summary, avoiding antibiotics is important for improving the gut microbiome. If antibiotics are essential, narrower-spectrum options should be preferred over broad-spectrum antibiotics.

Delaying antibiotic use is recommended when managing cytokine release syndrome, an adverse effect of cellular immunotherapy, although distinguishing this from neutropenic fever can be difficult. It is important to identify adverse effects correctly, avoid high-risk antibiotic use, and stop taking antibiotics at least 30 days before starting immunotherapy.

You can consider these 4 recommendations to support cancer treatment and healthy living:

1. Eat a fiber-rich diet containing a variety of plant foods (> 20 g per day).
2. Avoid artificial sweeteners as well as ultraprocessed (convenience) foods .
3. Eat meat only in moderation. Limit processed meats whenever possible.
4. Engage in regular physical activity, both aerobic and anaerobic.

Looking ahead, a more holistic, functional understanding and validated predictions are needed for treatment and diagnosis.

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