Explore how the gut microbiome influences cancer treatment response, immunotherapy outcomes, and therapy-related side effects.
Content Outline
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How the Microbiome Influences Cancer Development and Progression
Why The Microbiome Matters in Cancer Care
Cancer treatment has entered an unprecedented era of innovation, thanks to the introduction of immunotherapies, targeted drugs, and personalised medicine. Together, these have helped transform outcomes for many cancer patients, but responses can vary. Two people with the same diagnosis and the same treatment can get very different results. Why? Well, researchers believe one reason could be the gut microbiome.
The trillions of microorganisms that inhabit our gut could be an underappreciated factor in explaining the high variability in cancer treatment outcomes. For example, immune checkpoint inhibitors (ICIs) have revolutionized cancer care, yet just 20 to 40% of cancer patients respond to them, with early research suggesting that the gut microbiota are key to modulating the anti-tumour immune response.
A major review published in Nature Reviews Microbiology in January 2026 synthesises a rapidly expanding body of evidence showing that the gut microbiome plays a central role in cancer development, treatment response, and toxicity. Far from being a passive bystander, gut microbes help shape immune function, drug metabolism, and tumour biology — making the microbiome a promising target in future cancer care.
In this article, we explore what we currently know about the microbiome-cancer connection, how it influences treatment outcomes, and why microbiome-targeted strategies, like diet and probiotics, are gaining interest.
An Overview of the Link Between The Microbiome and Cancer
The gut microbiome is a complex ecosystem of microbes: bacteria, fungi, viruses, and protozoa that interact continuously with their host. These microbes produce many important compounds, like short-chain fatty acids (SCFAs) and vitamins, regulate immune responses, and help maintain the integrity of the gut barrier. However, when this ecosystem is unbalanced, known as dysbiosis, the consequences can be far-reaching, even beyond the digestive system.
Cancer and its treatments affect the microbiome and vice versa. Chemotherapy, radiotherapy, antibiotics, and dietary changes can all reduce microbial diversity and trigger compositional shifts. These changes can cause inflammation, a heightened immune response, and even initiate metabolic pathways that are linked to cancer progression. On the flip side, certain probiotic strains have shown potential to enhance the effectiveness of some cancer therapies in preclinical and early clinical studies (Fig.1).
Figure 1. Probiotics can regulate the biotransformation of cancer drugs to increase their efficacy and reduce their toxicity.
Animal studies haveA6A67 demonstrated that the microbiota can promote tumour growth in spontaneous, genetic, and carcinogen-related cancers across several organs, including the skin, colon, and lungs. While a healthy, balanced microbiome packed with commensal and symbiotic bacteria can prevent cancer development by competing with cancer-causing pathogens and metabolizing food into bioactive compounds, which have anti-inflammatory properties and maintain the integrity of the gut barrier (Fig.2).
Figure 2. Friendly bacteria can prevent cancer by outnumbering pathogenic microbes and delivering bioactive compounds. These can help prevent immune cell activation and maintain the integrity of the gut barrier.
How the Microbiome Influences Cancer Development and Progression
Historically, cancer-causing microbes were studied using frameworks such as Koch’s postulates, which focused on single pathogens. Today, however, researchers recognise that microbial communities — not just individual species — can collectively influence cancer risk by shaping inflammation, immunity, and metabolism.
Here are some of the ways bacteria can influence cancer development.
Genotoxicity
Opportunistic or pathogenic bacteria can colonize epithelial surfaces and exert cancer-causing effects through several mechanisms, such as direct host cell signalling, communication between microbes, and the production of secreted toxins, like tilimycin, indolimines, colibactin, and Bacteroides fragilis toxin (BFT).
Toxins such as colibactin can cause DNA double-strand breaks, triggering genomic instability and promoting cancer development, as seen in Figure 3.
Figure 3. Cancer cell development via microbe-mediated genotoxicity.
Epigenetic Modulation
The gut microbiome is able to shape gene expression and influence tumour behaviour via metabolic, inflammatory, and diet-microbiome interactions. One of the most common ways it does this is by modulating histone deacetylase (HDAC) inhibition via butyrate.
In healthy colon cells, butyrate serves as an energy source and helps regulate gene expression by inhibiting histone deacetylases (HDACs). In colorectal cancer cells, however, altered metabolism leads to butyrate accumulation, which can enhance HDAC inhibition and influence tumour cell proliferation and apoptosis.
HDAC inhibition has been proposed as a promising anti-cancer therapy, as HDAC effectively causes cells to commit suicide.
Figure 4. Dietary, metabolic, and inflammatory interactions with microbes can shape gene expression and tumour behaviour, making the gut microbiome a powerful epigenetic regulator.
Inflammation and Gut Barrier Dysfunction
Gut inflammation is strongly linked to gut barrier dysfunction, and inflammation can be caused by several factors, including chronic microbial infections, such as Helicobacter pylori. A compromised gut barrier may contribute to colorectal cancer development by allowing microbial products — such as lipopolysaccharide (LPS) and secondary bile acids — to enter circulation, where they can drive chronic inflammation or immune suppression.
Figure 5. Gut inflammation can weaken the gut barrier, allowing bacterial toxins and metabolites to cross into circulation, promoting inflammation, dampening the immune response, and enabling carcinogenesis.
On the other hand, metabolites, like SCFAs, can protect the gut barrier by stimulating mucus production and promoting the formation of tight junction proteins.
The Microbiome and Cancer Treatment Response
Various host- and tumour-related factors can influence cancer treatment outcomes. The gut microbiome is also an important contributor to the varied and individualised response to drug metabolism, which has expanded into its own designated field of research called pharmacomicrobiomics.
How the Gut Microbiome Affects Chemotherapy and Drug Metabolism
Like the human genome, the gut microbiome harbours a vast array of genes capable of metabolising medicines, including many cancer drugs. This means gut bacteria can directly influence how well treatments work and how toxic they are. For example, certain gut microbes can inactivate commonly used chemotherapy drugs such as 5-fluorouracil (5-FU) or gemcitabine, reducing their effectiveness. In other cases, bacteria can activate drugs too early or in the wrong place in the body, which may increase side effects. While microbial drug metabolism can sometimes reduce toxicity, it can also undermine treatment efficacy — highlighting the delicate balance between benefit and harm.
Cancer treatments don’t just interact with the microbiome — they also reshape it. Some chemotherapy drugs have antimicrobial effects that reduce beneficial bacteria and increase susceptibility to infections, while others damage the gut lining or nervous system, indirectly altering microbial communities. These changes can weaken the intestinal barrier, allowing bacteria and their products to leak into surrounding tissues and trigger inflammation. This process is linked to side effects such as mucositis, fatigue, and gastrointestinal symptoms, and may even influence cancer outcomes. Together, these findings show that cancer drugs, the microbiome, and the host are tightly interconnected, reinforcing the idea that cancer therapy affects — and is affected by — the entire host–microbiome system rather than acting solely on tumours.
How Gut Bacteria Influence Immunotherapy Response
The gut microbiome plays an important role in shaping the immune response to cancer treatments. It helps regulate the balance between immune activation and immune suppression in the gut, throughout the body, and within the tumour microenvironment. Through its effects on immune cells such as cytotoxic CD8⁺ T cells, dendritic cells, macrophages, and regulatory T cells, the microbiome can influence whether the immune system mounts an effective anti-tumour response or allows cancer cells to evade detection. These effects are mediated not only by direct immune signalling but also by changes in gut barrier integrity, inflammation, and the availability of nutrients and metabolites within tumours.
This immune modulation is particularly relevant for immunotherapies such as immune checkpoint inhibitors, which work by removing inhibitory “brakes” on T cells so they can attack cancer cells. Numerous studies have shown that the composition of the gut microbiome is linked to how well patients respond to these therapies. While different studies have identified different bacterial species associated with better outcomes, they often point to the same underlying effect: enhanced activation and infiltration of CD8⁺ T cells into tumours. This suggests that it may be microbial function — rather than specific bacterial names — that matters most. Different microbial communities can generate similar immunomodulatory metabolites or signals, leading to comparable treatment responses across individuals.
Microbial metabolites appear to be a key part of this process. Compounds such as short-chain fatty acids and products of amino acid metabolism can enhance CD8⁺ T cell activity and support anti-tumour immunity, although their effects depend on context. For example, some metabolites can strengthen immune responses under certain conditions but suppress immune responses in others. The local tumour environment also plays a crucial role: moderate inflammation can support immune attack, while chronic inflammation can exhaust immune cells and drive resistance to therapy. This highlights how closely microbial activity, immune tone, and tumour biology are intertwined.
The microbiome also influences treatment-related side effects and responses beyond immunotherapy. Evidence suggests that baseline gut microbiome composition is linked to the risk of immune-related adverse events, such as gut inflammation during checkpoint inhibitor therapy, although clear predictive microbial signatures have yet to be identified. Similar patterns are seen with chemotherapy, where specific microbial profiles have been associated with better treatment responses. Chemotherapy can damage the gut lining, allowing microbes or their products to interact with the immune system in ways that may either worsen side effects or enhance anti-cancer immunity. Together, these findings reinforce the idea that cancer therapies do not act on tumours alone, but operate within a complex host–microbiome–immune system that helps determine both their effectiveness and their risks.
Microbiome-Targeted Interventions in Cancer Care
As understanding of the microbiome’s role in cancer has grown, so too has interest in how it could be targeted or modulated to improve cancer care. Several strategies are being investigated, from dietary interventions to postbiotics and even faecal microbiota transplantations (FMT).
Dietary Interventions
Diet is one of the most powerful modulators of the human gut microbiome. A diet that is rich in natural plant fibers can support a diverse microbiome that produces an array of beneficial metabolites. The Be Gone study found that adding a daily cup of beans to an individual's usual diet increased the abundance of health-promoting bacteria, like Faecalibacterium, Bifidobacterium, and Eubacterium. This also led to increased bacterial metabolites and reduced inflammatory biomarkers.
Preclinical models have found that a ketogenic diet, that is a high-fat, low-carb eating pattern, can improve immunotherapy outcomes and provide anticancer effects. This is primarily through the ketone body β-hydroxybutyrate, promoting the expansion of CXCR3-activated T cells ,which are crucial for mounting immune responses against infections and cancer.
Other dietary interventions which could offer benefits in cancer therapy are polyphenols and vitamin D supplementation. Polyphenols feed specific gut inhabitants and can increase their abundance and boost immune cells. Vitamin D, on the other hand, can modulate the gut microbiome to enhance a cancer patient's response to immunotherapy and improve antitumour immunity.
Probiotics
Probiotics can be crucial tools for some of the toxic side effects associated with some cancer treatments, such as chemotherapy-induced diarrhea, but they can also increase the efficacy of immune checkpoint inhibitor (ICI) treatment.
One study demonstrated that the probiotic strain Lactobacillus reuteri can translocate to, colonize, and survive within melanoma and produce indole-3-aldehyde. This promotes IFNγ⁺ CD8⁺ T cell responses, which are critical for antitumour immunity (Figure 6).
Figure 6. L. reuteri can move into a melanoma tumor where it releases metabolites that boost antitumor immune responses, increasing ICI efficacy.
Another study found that the production of a tryptophan metabolite called indole-3-carboxylic acid by Lactobacillus gallinarum improved the efficacy of anti-PD-1 therapy. Anti-PD-1 therapy is a type of checkpoint inhibitor immunotherapy that blocks the programmed death-1 (PD-1) receptor on T cells, preventing cancer cells from suppressing the immune system.
Prebiotics
Prebiotics selectively feed beneficial bacteria already present in the gut. Human milk oligosaccharides (HMOs) are a unique class of structurally complex prebiotics that have been extensively studied for their ability to support beneficial bacterial communities and support immunity. Although much research has focused on early-life studies, emerging trials show the potential of these approaches to support the microbiome and adult health. One emerging area of interest is whether targeted prebiotics can help preserve gut barrier integrity during cancer treatment.
Recent research has demonstrated that a type of HMO called 2’-fucosyllactose (2’-FL) could prevent intestinal mucositis, a painful complication of chemotherapy and radiotherapy.
In the study, mice were injected with 5-fluorouracil (5-FU), a chemotherapy drug, to induce intestinal mucositis. The mice were then analysed 3 days later. 2’-FL was added to drinking water either 4 days before or at the same time 5-FU was administered to the mice.
The results showed that the addition of 2’-FL prevented intestinal mucositis, but mice given it 4 days in advance had a more pronounced response. The 2’-FL protected against:
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inflammation
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cytokine production
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intestinal lining cells apoptosis
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shortening of villi
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goblet cell loss
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tight junction disruption
These protective benefits are shown in Figure 7. The study also found that 2’-FL did not affect the efficacy of 5-FU.
Figure 7. Benefits of 2’-FL supplementation alongside chemotherapy.
Although not a treatment, prebiotic strategies are being explored as tools to support a positive microbial environment, which may improve health, wellness, and outcomes when used alongside conventional cancer therapies.
Faecal Microbiota Transplantation (FMT)
FMT involves transferring gut microbes from a healthy donor to a recipient. Small studies have shown that FMT can restore immunotherapy responsiveness in some people who had previously failed treatment. A recent study demonstrated that FMT can enhance the effectiveness of immunotherapy in people with advanced kidney cancer. After 1 year, 70% of patients who received FMT had no disease progression, compared with 41% in the placebo group. These findings suggest that FMT may be a promising adjunctive strategy in selected patients, though larger, longer-term studies are needed.
What This Means for the Future of Cancer Therapy
The human gut microbiome is emerging as a powerful, modifiable factor in many aspects of our health, including cancer care. As research progresses, microbiome-mediated strategies could help predict treatment response, reduce treatment toxicity, and enhance the effectiveness of existing therapies.
While microbiome-targeted interventions are not a replacement for conventional cancer treatments, they represent an important new dimension in supportive and personalized cancer care. Tools such as artificial intelligence (AI) could, one day, become part of novel diagnostic tools or personalized treatment strategies. With continued investment in well-designed clinical trials and mechanism-driven research, harnessing the microbiome may become an integral part of cancer treatment in the years ahead.
Summary
The gut microbiome is increasingly recognised as a powerful modulator of cancer development, treatment response, and therapy-related side effects. From influencing immune checkpoint inhibitor efficacy to shaping chemotherapy metabolism and protecting gut barrier integrity, microbial communities play an active role in determining outcomes. Emerging research suggests that targeted microbiome-supportive strategies — including dietary approaches, probiotics, prebiotics such as human milk oligosaccharides (HMOs), and even faecal microbiota transplantation — may help optimise the treatment environment when used alongside conventional cancer therapies.
As oncology moves toward more personalised and precision-based care, understanding and supporting the gut microbiome could become an important part of improving resilience, reducing toxicity, and enhancing therapeutic effectiveness.
Written by: Leanne Edermaniger M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
