Probiotics in Cancer Treatment
Probiotics in cancer treatment is a relatively new possibility. Do not assume that they can replace your oncology team or recommended treatments, however.
If you have read my website, books, or newsletters for any period of time, you know that research shows that probiotics can be rock stars for health. You also know that research on probiotics is increasing at such an incredible rate that nearly every day brings new studies with new insights. Such is the case with probiotics and cancer. Some of the subsets of articles for probiotics and cancer are for prevention, treatment, immunotherapy specifically, cancer surgery, and therapy-related infections. I will focus primarily on probiotics in cancer treatment.
In order to give an general overview of how probiotics can be beneficial in cancer treatment, I have selected articles for various types of cancer that I believe capture the essence of how probiotics may be an adjuvant to traditional cancer therapies, particularly in human studies when those studies were available. Unfortunately, there is not available research for every type of cancer - yet. Nor could I possibly cover every type of cancer in one article even if research were available.
Each type of cancer in each individual patient requires an individualized approach, but this overview will assist you in conversations with your oncology team. Note that most of the studies are experimental/preclinical (in vitro or animal) in nature since cancer-related probiotics research is relatively recent. Thus, there are not many human clinical trials to date. Note also that the specific mechanisms involved in the probiotics’ benefits in each study are extremely detailed and beyond the scope of what non-oncology experts need to understand, so I will present the gist of how probiotics helped.
One general thing to understand in reading the summary of these studies is that a type of immune cell called a T-cell is extremely important in resolving cancer.
Probiotics in Cancer Treatment - Breast Cancer
A study in mice modeling stage 4 breast cancer showed that oral administration of two probiotics, Clostridium butyricum and Akkermansia muciniphila, reduced tumor volume and weight, particularly when both probiotics were administered. Survival rate was significantly increased in the dual-probiotic group. This was accomplished by activating the antitumor immunity and reshaping the tumor microenvironment, not by the probiotics entering the tumor.
Probitics in Cancer Treatment - Colorectal Cancer
A meta-analysis of 633 colorectal cancer (CRC) patients across 8 studies found that probiotics significantly decreased the incidence of chemoradiotherapy-induced diarrhea and improved pain index, heartburn, and insomnia compared to controls. No significant differences between the two groups were found for abdominal distension, inflammation of mouth and lips, fatigue, loss of appetite or quality of life scores. The probiotics used varied widely. For example, one study used 250 ml of kefir twice daily for one week during chemotherapy while another used 10 billion CFU three times daily for a duration of 12 weeks during chemotherapy.
Another review of 23 randomized, controlled trials of CRC showed that probiotics improved quality of life, enhanced gut microbial diversity, reduced postoperative infection complications, and decreased pro-inflammatory cytokine production regardless of the stage of cancer.
An in vitro and mouse study showed that Lactobacillus rhamnosus GG, a well-studied probiotic in the probiotic supplement Cuturelle, protects the intestine from radiation damage by producing lipoteichoic acid, which is protective to intestinal crypts (valleys between villi) through immune activation, but not to cancer cells.
Another mouse study showed that Lacticaseibacillus rhamnosus Probio-M9 increased the activity of an immune checkpoint inhibitor. It achieved this by promoting the beneficial microbes Lactobacillus and Bifidobacterium animalis, by increasing beneficial metabolites such as butyrate in the gut, and by promoting substances in the blood that promoted infiltration and activation of cytotoxic T-cells and suppressed regulatory T-cells that would hinder the cytotoxic ones. Once the gut bacteria or intestinal metabolites from treated mice were transplanted to new tumor-bearing mice, the same enhanced immune reaction was noted.
A randomized, single-blind, placebo-controlled study in 100 CRC patients who were provided post-operative probiotics while undergoing chemotherapy showed that probiotics reduced chemotherapy-induced gastrointestinal complications, particularly diarrhea, compared to placebo. While chemotherapy reduced the gut bacterial diversity and beneficial species, probiotics significantly increased diversity and restored the beneficial species. Probiotics administration also dramatically promoted the production of short-chain fatty acids such as acetate, butyrate, and propionate compared to placebo. The probiotics used were a combination of B. infants, L. acidophilus, E. faecalis, and B. cereus from Hangzhou Grand Biologic Pharma.
A randomized study in 52 CRC patients at four weeks post-surgery showed that those who took 30 billion CFU of probiotics twice daily for six months had significant reductions in the level of pro-inflammatory cytokines compared to pretreatment levels, which protected the intestines from immune damage. The probiotics were Lactobacillus acidophilus BCMC 12,130, Lactobacillus lactis BCMC 12,451, Lactobacillus casei BCMC 12,313, Bifidobacterium longum BCMC 02120, Bifidobacterium bifidum BCMC 02290 and Bifidobacterium infantis BCMC 02129.
Probiotics in Cancer Treatment - Gastric Cancer
A meta-analysis of studies evaluating the effects of probiotics on gastric cancer-related inflammation in humans showed that probiotics (Bifidobacterium, Lactobacillus, Streptococcus) can reduce gastric cancer-related inflammation levels by increasing a type of receptor for immune T-cells and decreasing an inflammatory chemical messenger.
In a randomized trial of a probiotic combination in patients with partial stomach removal due to gastric cancer, the probiotics significantly reduced inflammation while markedly increasing immunity and nutrition indexes. The probiotics also significantly enhanced the numbers of beneficial bacteria besides the probiotic species.
Probiotics in Cancer Treatment - Kidney Cancer
Kidney cancer treatments usually consist of multiple targeted-therapy agents (TT) and immune checkpoint inhibitors (ICI). One study showed that greater gut microbial diversity was associated with benefit from ICI, and that the relative abundance of the commensal Akkermansia muciniphila increased in patients who benefitted from ICI. In fact, Akkermanisa mucinophila was one of the main organisms associated with response to treatment in several studies in patients with metastatic renal cancer. Bifidobacterium species were another commensal associated with a positive response to ICI.
Another study showed that melanoma patients with Ruminococcaceae bacteria, known fiber degraders, were more abundant in responders versus non-responders to ICI treatments. In this same study article, but in a mouse study in a melanoma model, mice treated with ICI that were fed a fiber-rich diet had delayed tumor outgrowth compared with mice who received a fiber-poor diet. This did not happen in germ-free mice, so it was obvious that the response to the ICI was dependent on gut microbiota, and fiber-rich diets supported the gut microbes that increased ICI efficacy.
In a small metastatic renal cancer phase 1 trial, 29 patients (mostly males) were treated with nivolumab and ipilimumab, and some of them were randomized to additionally receive a probiotic. Patients who responded to the live probiotic Clostridium butyricum CBM588 in addition to the aforementioned medications as cancer treatment showed an increase in Bifidobacterium species, higher objective response rates and prolonged progression-free survival at the average 12-month mark. The authors stated that larger studies are needed to confirm these results.
Probiotics in Cancer Treatment - Liver Cancer
In a mouse model of liver cancer, Prohep probiotic significantly slowed tumor growth and reduced tumor size and weight by 40% compared with control. Prohep is a combination of the probiotics Lactobacillus rhamnosus GG, viable Escherichia coli Nissle 1917, and heat-inactivated VSL#3 (1:1:1).
Probiotics in Cancer Treatment - Lung Cancer Secondary to Melanoma
Melanoma can metastasize (relocate) to other places in the body such as the lungs. Lung microbiota regulate the body's response to inhaled substances to improve immune tolerance (prevention of immune overactivation and lung damage from benign substances. In a mouse model, aerosolized probiotics or antibiotics reduced the bacterial load in the lungs, which enhanced T-cells and natural killer cells, that in turn significantly reduced the metastasis of melanoma to the lungs. Both treatments also improved chemotherapy against advanced metastasis.
Additionally, when bacteria from antibiotic-treated mice were transplanted into other mice with melanoma, a significant reduction in the number of lung metastases was found. However, there was a significant reduction in immune tolerance in the lungs of the antibiotic-treated mice. We know that antibiotics can severely reduce beneficial gut microbes, and cause antibiotic resistance with primarily pathogenic species surviving the treatment. To avoid such a case, the researchers tried using a probiotic.
The probiotic Lactobacillus rhamnosus GG was aerosolized, and it significantly reduced the number of lung metastases when administered prior to melanoma initiation. The probiotic also retained the immune tolerance of the lungs. This showed that the probiotic had a preventive effect and also did not disrupt the normal immune regulation of the lungs.
Probiotics in Cancer Treatment - Melanoma
In mice, oral administration of a mix of Bifidobacterium breve and longum alone improved tumor control to the same degree as an immune checkpoint blockade, and the combination of the two therapies nearly eliminated tumor outgrowth. The mechanism of the probiotic was to improve tumor-specific immunity and response to the immune checkpoint. Live bacteria were required; heat-killed microbes did not have the same effect. This study showed that ORAL probiotics improved the body's ability to deal with cancer, even if the cancer was not in the gastrointestinal tract, because most of the immune system resides in the gastrointestinal tract.
In a phase 1 trial utilizing fecal microbiota transplantation (FMT) from a healthy donor with checkpoint inhibitors nivolumab or pembrolizumab in 20 previously-untreated advanced melanoma patients, no grade 3 adverse events were noted from FMT alone. Grade 3 adverse effects are severe but not immediately life-threatening. Five patients had grade 3 immune-related adverse events from combination therapy. The objective response rate was 65% (13 of 20) including four (20%) complete responses. Microbial profiling showed that all patients retained strains from the FMT, but the gut microbial changes that more closely resembled the donor (with more immune-beneficial bacteria and less pathogenic bacteria) occurred only in the responders to the treatment. Thus, using FMT from a healthy donor may increase the efficacy of immune checkpoint therapies for melanoma and possibly other cancers.
Probiotics in Cancer Treatment - Nasopharyngeal Cancer
Seventy-seven patients with nasopharyngeal cancer in a randomized, double-blind, placebo-controlled trial received a probiotic cocktail twice daily or placebo for 7 weeks from the first day of chemoradiotherapy to the end of treatment. The probiotic group had significantly lower oral mucositis (inflammation of the mucosa in the oral cavity) and less reduction of immune T-cells compared to the placebo group. The probiotic cocktail was a mix of one billion CFU each of L. plantarum MH-301, B. animalis subsp. lactis LPL-RH, L. rhamnosus LGG-18, and L. acidophilus, all strains from Chinese company Harbin Meihua Biotech.
A meta-analysis from 8 randomized, controlled trials with 691 patients on the efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients performed years after the aforementioned study showed the same promising results. Probiotics significantly reduced the incidence of severe oral mucositis, but not overall incidence of oral mucositis. There was greater benefit with a multi-strain formula than a single-strain formula.
Probiotics in Cancer Treatment - Pancreatic Cancer
Gencitabine (Gemzar and others) is an antimetabolite drug that disrupts DNA formation that is commonly used in breast, non-small cell lung, ovarian, and pancreatic cancers. It has been shown, in a mouse model of pancreatic cancer, to shift the intestinal microbiome toward an inflammatory state.
The effects of gemcitabine alone, probiotics alone, or gemcitabine+probiotics were tested in a mouse model of pancreatic cancer compared to non-treated control mice. All the treatments tended to decrease the growth of tumors compared to control, although the tumors still grew with time. Amazingly, probiotics alone performed similarly to gemcitabine.
Mice treated with gemcitabine alone had intestinal damage. However, mice in the two categories treated with probiotics showed regenerative changes in intestinal damage and richness in microbiota that produce short-chain fatty acids.
While gemcitabine treatment alone caused red blood cell count and platelets to drop, the addition of probiotics restored those molecules. Probiotics also partially rescued mitochondrial respiration and relieved some adverse effects of gemcitabine.
The researchers used a specially-formulated probiotic blend consisting of 100 million CFU each of B. breve SGB 01 and B. bifidum SGB 02, 750 million CFU each of L. kefiri SGL 13, L. plantarum SGL 07, L. salivarius SGL 03, and L. reuteri SGL 01, 0.51 mg of lactoferrin, and 2.3 mg of inulin.
Conclusions and Final Thoughts about Probiotics in Cancer Treatment
Probiotics in cancer treatment have the potential to not only help with side effects of cancer treatments, but also can work alongside certain chemotherapy drugs, such as immune checkpoint inhibitors, to activate and enhance their effects. Additionally, some of the studies in mice showed that an oral probiotic blend alone was able to decrease tumor size.
This does not mean that probiotics in cancer treatment should be a standalone treatment, however.
In fact, please do not start any probiotic routine without consulting your oncology team first. Probiotics may be helpful in many ways, including the modulation of the gut microbiome; prevention of the metabolism of carcinogenic substances; improvement of cancer drug treatment efficacy; enhancement of detoxification capabilities; exertion of anti-inflammatory action; immunopotentiator properties; antioxidant activities; prevention of tumor growth; and decreasing the adverse effects of chemotherapy. However, the actions of some probiotics may act against the cancer treatment your oncology team is trying to achieve.
Probiotics may also act differently in cancer patients than in healthy people since cancer patients have compromised immunity. There may be concerns of the risk of opportunistic infections, as well as the potential transfer of antibiotic resistance. Additionally, research into probiotics and cancer treatment is in its infancy, so the nuances of when or if to introduce probiotics, especially when antibiotics are administered, needs to be elucidated, particularly since antibiotic administration before the administration of ICI appears to reduce overall survival. Furthermore, non-specific probiotic supplementation (random microbes, dosages and regimens among patients) did not appear to make a significant difference in melanoma patients. Finally, different types of cancer require different approaches. One size does not fit all. Thankfully, research is continuing in this area and hopefully more results will be proven.
As I have stated many times, cancer is a complicated disease. However, gut health will continue to play important roles in cancer prevention, diagnosis, and treatment. Nutrition is and will continue to be critical, also, not only for the fiber that a whole-foods diet can contribute to sustaining favorable gut microbiota, but also for the nutrients that are critical for cancer patients. I believe that probiotics will continue to provide benefits for gut health, nutrition status, and overall health and will someday be routinely administered in treatments for diseases. But always remember, probiotics are live organisms that require a diet high in fiber and polyphenols from whole plant foods in order to maximize their potential.
If you do not have cancer, now is the best time to try to prevent it. Prevention, while sometimes viewed as boring by the jet-set crowd, is the best way to take care of yourself. Vegetables are your friends, they really are. :)
References:
- R. Yang at al. "Evaluation of the efficacy of probiotics in the chemoradiotherapy of colorectal cancer: a meta-analysis of Randomized Controlled Trials," BMC Gastroenterol 25.1 (2025).
- I.J. Dikeocha et al. " Probiotics supplementation in patients with colorectal cancer: a systematic review of randomized controlled trials," Nutr Rev 80.1 (2021).
- T.E. Riehl et al. "Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells," Gut 68.6 (2019).
- G. Gao et al. "Lacticaseibacillus rhamnosus Probio-M9 enhanced the antitumor response to anti-PD-1 therapy by modulating intestinal metabolites," eBioMedicine 91 (2023).
- F. Huang et al. "Postoperative Probiotics Administration Attenuates Gastrointestinal Complications and Gut Microbiota Dysbiosis Caused by Chemotherapy in Colorectal Cancer Patients," Nutrients 15.2 (2023).
- L. Zaharuddin et al. "A randomized double-blind placebo- controlled trial of probiotics in post-surgical colorectal cancer," BMC 19 (2019).
- D. Yang eat al. "Effects of probiotics on gastric cancer-related inflammation: A systematic review and meta-analysis," J Food Biochem. 46.5 (2022).
- C. Zheng et al. "A randomised trial of probiotics to reduce severity of physiological and microbial disorders induced by partial gastrectomy for patients with gastric cancer," J Cancer 10.3 (2019).
- L. Meza et al. "The Gut Microbiome and Metastatic Renal Cell Carcinoma," J Clin Med. 12.4 (2023).
- N.J. Salgia et al. "Stool Microbiome Profiling of Patients with Metastatic Renal Cell Carcinoma Receiving Anti–PD-1 Immune Checkpoint Inhibitors," European Urology 78.4 (2020).
- C.N. Spencer et al. "Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response," Science 374.6575 (2021).
- N. Dizman et al. "Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial," Nature Medicine 28 (2022).
- J. Li et al. "Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice," Front Oncol. (2021).
- V. Le noci et al. " Modulation of Pulmonary Microbiota by Antibiotic or Probiotic Aerosol Therapy: A Strategy to Promote Immunosurveillance against Lung Metastases," Cell Rep. 24.13 (2018).
- A. Sivan et al. "Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy," Science 350.6264 (2015).
- B. Routy et al. "Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial," Nat Med. 29.8 (2023).
- C. Xia et al. "A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma," Front Immunol. 12 (2021).
- P. Lin et al. "Efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients: A systematic review and meta-analysis," Microb Pathog (2024).
- D. Panebianco et al. "Tuning gut microbiota through a probiotic blend in gemcitabine-treated pancreatic cancer xenografted mice," Clinical and Translational Medicine September 7, 2021.
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