The Gut Microbiome and Cancer: What This New Study Tells Us—and Why It Matters

Summary of Hazan et al., 2026

Gut Microbiome Alterations in Cancer and Non-cancer Adults: A Cross-Sectional Metagenomic Study. (1)

Interest in the gut microbiome has exploded over the past decade. We now appreciate that the trillions of microorganisms inhabiting the human gastrointestinal tract are not innocent bystanders but active participants in immune regulation, metabolism, inflammation, and even cancer biology. The study by Hazan and colleagues adds another piece to this rapidly evolving puzzle.

The investigators performed a cross-sectional metagenomic analysis of stool samples from 60 adults, including 20 healthy controls, 15 patients with non-aggressive cancers, and 25 patients with aggressive cancers. Rather than focusing on one cancer type, the study included a broad spectrum of malignancies including breast, colorectal, ovarian, prostate, lymphoma, lung, bladder, thyroid, leukemia, and others.

Major findings

Patients with aggressive cancers demonstrated a characteristic pattern of gut dysbiosis:

• Markedly reduced Bifidobacterium

• Reduced Faecalibacterium

• Reduced Collinsella

• Increased Bacteroides

These differences reached statistical significance. Patients with less aggressive cancers showed a similar trend, although most comparisons did not reach significance, likely because of the small sample size.

Perhaps the most striking observation was the profound reduction in Bifidobacterium, falling from approximately 6.5% of the gut microbiome in controls to only 1.2% in aggressive cancers.

Why these bacteria matter

Bifidobacterium

Bifidobacteria are among the best-studied beneficial intestinal organisms.

They:

• strengthen the intestinal barrier

• produce short-chain fatty acids

• suppress pathogenic bacteria

• enhance dendritic cell maturation

• stimulate CD8 T-cell responses

• improve interferon production

• enhance anti-tumor immunity

Animal studies have shown that simply restoring Bifidobacterium can improve responses to immune checkpoint inhibitors.(2)

Faecalibacterium

Faecalibacterium prausnitzii is one of the major producers of butyrate, the principal fuel for colonocytes.

Butyrate:

• reduces intestinal inflammation

• strengthens epithelial tight junctions

• inhibits NF-κB activation

• promotes regulatory immune balance

• possesses direct anti-neoplastic effects through epigenetic mechanisms

Several immunotherapy studies have associated higher Faecalibacterium abundance with better outcomes in melanoma and hepatocellular carcinoma.(3, 4)

Collinsella

Although less well studied, Collinsella has increasingly been linked with favorable responses to immunotherapy.

Patients responding to PD-1 blockade often have higher baseline Collinsella abundance than non-responders.(5)

Bacteroides

The picture for Bacteroides is considerably more complicated.

Some species appear beneficial, while others promote:

• chronic inflammation

• immune suppression

• carcinogen production

• DNA damage

• bile acid metabolism favoring tumor growth

The current study found substantially higher Bacteroides levels in aggressive cancers, but it could not determine which species were responsible.

Strengths of the study

The investigators used shotgun metagenomic sequencing, providing much greater taxonomic resolution than traditional 16S sequencing.

The inclusion of numerous cancer types suggests these microbial changes may represent a common cancer-associated pattern rather than being unique to one malignancy.

Importantly, the study also distinguished between aggressive and non-aggressive tumors.

Important limitations

This remains an exploratory observational study.

Major limitations include:

• only 60 participants

• cross-sectional design

• heterogeneous cancer types

• controls were substantially younger

• dietary differences not measured

• medication use not controlled

• prior antibiotics not evaluated

• chemotherapy and immunotherapy effects unknown

Most importantly:

The study cannot determine whether microbiome abnormalities cause aggressive cancer or whether advanced cancer causes microbiome disruption.

This distinction is critical.

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The Gut Microbiome and Cancer: A Review

The microbiome as a forgotten organ

The human gut contains roughly 40 trillion microorganisms, encoding over 100 times more genes than the human genome.(6)

Rather than existing as passive passengers, these organisms function almost as an additional organ.

They regulate:

• immune maturation

• inflammation

• epithelial integrity

• metabolism

• bile acids

• vitamins

• neurotransmitters

• drug metabolism

Disturbances of this ecosystem—dysbiosis—have now been linked with obesity, diabetes, autoimmune disease, neurodegeneration, cardiovascular disease, and many cancers.(6)

Within the framework of the metabolic theory of cancer, the microbiome may represent another major environmental regulator of the tumor microenvironment.

How the microbiome influences cancer

Several biological pathways are now recognized.(7, 8)

1. Chronic inflammation

Certain bacteria activate:

• NF-κB

• IL-6

• TNF-α

• STAT3

creating a persistent inflammatory state that promotes tumor initiation and progression.

2. Immune surveillance

Beneficial organisms enhance:

• dendritic cell activation

• NK-cell function

• CD8 T-cell responses

• interferon signaling

Conversely, dysbiosis favors:

• regulatory T cells

• myeloid-derived suppressor cells

• immune exhaustion

This directly affects tumor immune surveillance.

3. Metabolic regulation

Gut bacteria produce numerous metabolites including:

• butyrate

• acetate

• propionate

• indoles

• secondary bile acids

These molecules influence:

• mitochondrial function

• oxidative stress

• insulin sensitivity

• glucose metabolism

• epigenetic regulation

Many intersect with pathways central to the metabolic theory of cancer.

4. Response to immunotherapy

Perhaps the strongest evidence for clinical importance comes from immune checkpoint inhibitors.

Multiple independent studies have demonstrated that patients with microbiomes enriched in:(2, 5, 9)

• Bifidobacterium

• Faecalibacterium

• Akkermansia muciniphila

experience:

• higher response rates

• longer progression-free survival

• improved overall survival

during PD-1/PD-L1 therapy.

Remarkably, fecal microbiota transplantation (FMT) from immunotherapy responders has restored responsiveness in some patients whose cancers were previously resistant.(10)

Can probiotics help?

This is where enthusiasm should be tempered with scientific caution.

Potential benefits

Certain probiotic strains have demonstrated the ability to:

• reduce chemotherapy-associated diarrhea

• decrease antibiotic-associated diarrhea

• improve intestinal barrier integrity

• reduce systemic inflammation

• increase butyrate production

• enhance NK-cell activity

• improve dendritic cell function

Several small trials suggest probiotics may reduce postoperative infections after colorectal surgery and lessen radiation-induced gastrointestinal toxicity.(11)

Evidence for preventing cancer progression

Here the evidence remains limited.

Animal studies are encouraging.

Several human studies suggest improved immune function.

However, there is currently no convincing evidence that commercially available probiotics alone slow cancer progression or improve survival.

That is an important distinction.

Synbiotics

Combining probiotics with fermentable fibers (prebiotics) appears more promising.

Prebiotics nourish beneficial bacteria already present in the intestine, allowing longer-term colonization and increased production of anti-inflammatory metabolites.

Diet remains more important than probiotics

Perhaps the greatest determinant of the microbiome is diet.

Beneficial organisms flourish with diets rich in:

• diverse vegetables

• resistant starch

• polyphenols

• fermented foods

• omega-3 fatty acids

Conversely, Western dietary patterns characterized by ultra-processed foods, excess refined sugar, emulsifiers, and low fiber are consistently associated with reduced microbial diversity and increased inflammatory species.

For many patients, dietary modification is likely to exert a greater long-term impact on the microbiome than probiotic supplementation alone.

Where this fits within the Five-Axis Metabolic Trap

The microbiome integrates naturally into the Five-Axis Metabolic Trap model.

A healthy microbiome can:

• Axis 1: Improve insulin sensitivity and reduce glycolytic signaling through production of short-chain fatty acids.

• Axis 2: Support mitochondrial health by generating metabolites such as butyrate that enhance oxidative metabolism.

• Axis 3: Reduce inflammatory cytokines and oxidative stress, making tumor cells more susceptible to apoptosis.

• Axis 4: Modulate the tumor microenvironment by limiting chronic inflammation and immune suppression.

• Axis 5: Strengthen innate and adaptive antitumor immunity, improving NK-cell, dendritic cell, and CD8 T-cell function while potentially enhancing responses to immunotherapy.

Rather than acting as a stand-alone treatment, the microbiome should be viewed as another component of a comprehensive systems-based approach to cancer care.

Bottom line

The Hazan study provides further evidence that patients with aggressive cancers harbor a distinct pattern of gut dysbiosis characterized by depletion of beneficial organisms such as Bifidobacterium, Faecalibacterium, and Collinsella, together with enrichment of Bacteroides.

Although the study cannot establish causality, it aligns with a growing body of literature suggesting that the gut microbiome influences tumor biology, systemic inflammation, and responses to anticancer therapy. The most compelling clinical evidence to date relates to immunotherapy, where microbiome composition appears to affect treatment efficacy. Maintaining a healthy microbiome through dietary measures, minimizing unnecessary antibiotic exposure, and judicious use of selected probiotics or synbiotics may represent valuable adjunctive strategies within an integrative oncology program, but current evidence does not support probiotics as a substitute for established cancer therapies.

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References

1. Hazan S, Bao G, Goudzwaard A, Ichim T, Martin L, Vidal AC. Gut Microbiome Alterations in Cancer and Non-cancer Adults: A Cross-Sectional Metagenomic Study. Technol Cancer Res Treat. 2026;25:15330338261470516.

2. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084–9.

3. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103.

4. Zheng Y, Wang T, Tu X, Huang Y, Zhang H, Tan D, et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J Immunother Cancer. 2019;7(1):193.

5. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104–8.

6. Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016;375(24):2369–79.

7. Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med. 2019;25(3):377–88.

8. Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. Cancer Cell. 2018;33(4):570–80.

9. Hes C, Jagoe RT. Gut microbiome and nutrition-related predictors of response to immunotherapy in cancer: making sense of the puzzle. BJC Rep. 2023;1(1):5.

10. Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021;371(6529):602–9.

11. Liu PC, Yan YK, Ma YJ, Wang XW, Geng J, Wang MC, et al. Probiotics Reduce Postoperative Infections in Patients Undergoing Colorectal Surgery: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2017;2017:6029075.