Clostridium butyricum MIYAIRI 588 (CBM588 / MIYA-BM® / Butirrisan®)

Clostridium butyricum MIYAIRI 588 strain (CBM588)
Evidence Level
Limited
5 Clinical Trials
7 Documented Benefits
2/5 Evidence Score

Clostridium butyricum MIYAIRI 588 (CBM588) is a butyrate-producing probiotic strain marketed as MIYA-BM® and Butirex C4 (Japan). Despite the 'Clostridium' name suggesting pathogen (C. difficile), C. butyricum MIYAIRI 588 is a non-pathogenic butyric acid-producing strain with decades of use in Japan and growing global research interest. Its distinguishing feature is that it makes butyrate, a short chain fatty acid that the cells lining the colon use for fuel. That is well described laboratory biology, but it is not the same thing as a proven health benefit in people. The published human evidence is much thinner than that suggests. One study from 2003 in children taking antibiotics reported less antibiotic-associated diarrhea. No trial in irritable bowel syndrome has published results. Everything else comes from cancer medicine: two small phase 1 trials of 30 people each, in patients with advanced kidney cancer who were all receiving prescription cancer drugs including immunotherapy, plus one observational lung cancer study. Both phase 1 trials missed their main goal. The honest framing: a long-used, generally well tolerated probiotic with a plausible mechanism but very little published human evidence, and what exists was mostly collected in seriously ill patients under specialist care. In Japan, MIYA-BM is a prescription product rather than a supplement, and any findings apply only to this one strain, CBM588.

Studied Dose 20-80 mg/day MIYA-BM® powder (1-4×10⁸ CFU) is the dose range cited for the Japanese product MIYA-BM, which is sold there as a prescription product. No adult dose is established by the studies cited on this page: the antibiotic-associated diarrhea study was done in children, and the cancer trials were run under oncology supervision.
Active Compound Clostridium butyricum MIYAIRI 588 strain (CBM588); a butyrate-producing spore-forming probiotic.

Benefits

Butyrate production in the gut

This strain makes butyrate, a short chain fatty acid that the cells lining the colon use for energy. That sets it apart from lactic acid probiotics such as Lactobacillus and Bifidobacterium. This is laboratory biology: none of the studies cited on this page measured butyrate levels or gut health in healthy adults.

Antibiotic-associated diarrhea prevention

One study from 2003, in children taking antibiotics, reported fewer cases of antibiotic-associated diarrhea (PMID 12654076). That is the only human study of this use cited here, it is more than twenty years old, and it was not done in adults. The spore form is expected to survive stomach acid and concurrent antibiotics better than typical probiotics.

Irritable bowel syndrome: results not yet published

No published trial supports this. One 8 week trial in people with diarrhea-predominant irritable bowel syndrome (NCT06676514) has finished, but its results have not been published, so there is nothing yet to report about symptoms or stool consistency. Ongoing bowel symptoms should be assessed by a doctor rather than self-treated.

What the cancer trials actually showed (phase 1 studies in patients on prescription cancer drugs)

Two small phase 1 trials, 30 people each, gave CBM588 to patients with advanced kidney cancer who were already receiving prescription cancer drugs (nivolumab with ipilimumab in 2022, cabozantinib with nivolumab in 2024). Both trials missed their main goal: there was no significant change in Bifidobacterium levels or in overall gut bacteria diversity. The differences in tumor response were secondary findings, and in the 2022 trial that difference was not statistically significant (58% versus 20%, P=0.06). The authors describe the results as a preliminary signal needing confirmation. A separate lung cancer study was observational, so it shows an association, not an effect. None of this shows that a probiotic treats cancer or improves survival, and nobody with cancer should start or stop anything without their oncologist.

Inflammatory bowel disease: no evidence cited here

No trial in inflammatory bowel disease is cited on this page, so there is nothing here to back this up. Inflammatory bowel disease is a serious medical condition that needs care from a doctor, and a probiotic is not a substitute for prescribed treatment.

Gut barrier function support

In laboratory and animal work, butyrate helps tighten the junctions between the cells lining the colon. That is the proposed reason people are interested in this strain. Gut permeability and inflammation were not measured in any of the human studies cited on this page.

Decades-long Japanese safety record

This strain has been used in Japan since the 1960s, where MIYA-BM is a prescription product rather than a supplement. Long real-world use is reassuring, but it is not the same as a controlled long-term safety study, and no such study is cited on this page.

Mechanism of action

1

Butyrate production (distinguishing from Lactobacillus/Bifidobacterium)

C. butyricum is a butyrate producer — distinct from the lactic-acid-producing Lactobacillus and Bifidobacterium probiotics. Butyrate is the primary energy source for colonocytes (60-70% of their energy), and in laboratory studies it affects enzymes involved in inflammation. This is the proposed explanation for why the strain might matter, not a result demonstrated in the human studies cited here.

2

Spore formation with heat and acid resistance

Like other Clostridium species, C. butyricum forms endospores resistant to gastric acid, bile, and heat — enabling reliable transit through the upper GI tract to the colon where it germinates and exerts effects.

3

C. difficile inhibition (laboratory findings only)

In laboratory work, CBM 588 lowered succinate (a nutrient C. difficile uses to grow), acted alongside the antibiotic fidaxomicin, and reduced toxin activity in test tubes. None of this has been shown in a human trial cited on this page, and C. difficile infection is a serious condition that needs prompt medical care and prescription antibiotics.

4

Mucin layer protection and production

In animal and laboratory studies, CBM 588 supported the mucus layer that separates gut bacteria from the gut wall. A healthy mucus layer is thought to help keep bacteria where they belong. This was not measured in any of the human studies cited on this page.

5

TNF-α downregulation and IgA upregulation

In laboratory and animal work, CBM 588 lowered TNF-alpha (an inflammatory signal) in immune cells of the gut wall and raised production of IgA, an antibody that coats the gut lining. These are preclinical observations. They have not been shown to make people more resistant to infection, and no human study cited here measured immune outcomes.

6

Cross-feeding support of beneficial commensals

In laboratory studies, substances made by CBM 588, including butyrate, helped other gut bacteria such as Bifidobacterium and Lactobacillus grow. Worth knowing: the two cancer trials cited on this page did measure Bifidobacterium in people, and found no significant increase. That was the main goal of both trials, and both missed it.

7

Cancer-related laboratory pathways (no human results)

In the laboratory, butyrate affects several cell pathways that researchers think might matter in bowel cancer. That reasoning is why a trial on polyp recurrence was started. The trial is still enrolling and has produced no results. There is no evidence that this probiotic prevents or treats any cancer, and it is not a substitute for colonoscopy or medical care.

Clinical trials

1
Laboratory study of C. difficile resistance (not a human trial)

Nature Scientific, doi:10.1038/s41598-021-94572-z.

Clinical population described in trial publication.

Nature Scientific, doi:10.1038/s41598-021-94572-z. In laboratory work, CBM 588 improved resistance to C. difficile through changes in metabolism and immune signaling: it enhanced the antibacterial activity of fidaxomicin in the lab, negatively modulated gut succinate (substrate for C. difficile), downregulated colon-resident macrophage TNF-α, upregulated IgA through IL-17A CD4+ T cells and plasma B cells, and strengthened the gut lining. This was a laboratory study, not a human trial, and it is not among the four PubMed references listed on this page. It does not show that taking this probiotic prevents C. difficile infection in people.

2
NCT06676514 PROREDI — Butirrisan® IBS-D 8-Week Clinical Trial

Liaquat University Pakistan, completed.

Clinical population described in trial publication.

Liaquat University Pakistan, completed. This registered trial compared Butirrisan, 3 tablets a day for 8 weeks, against standard care (the prescription drug trimebutine plus a lactose free, low residue diet) in people with diarrhea-predominant irritable bowel syndrome. No results have been published, so nothing is known yet about whether it helped. There was no placebo group.

3
NCT01077245 — US Phase 2 CDI Clinical Trial (Withdrawn)

Osel Inc Phase 2 clinical trial in CDI recurrence using MIYA-BM at 2 g BID for 42 days.

Clinical population described in trial publication.

Osel Inc Phase 2 clinical trial in CDI recurrence using MIYA-BM at 2 g BID for 42 days. The trial was withdrawn and produced no data at all. The listed reason was low enrollment rather than a safety problem, but the practical point is simple: there is no US trial evidence for this use.

4
NCT06855355 — Colorectal Polyp Recurrence (Enrolling)

Kaohsiung Medical University randomized crossover trial, currently enrolling by invitation.

Clinical population described in trial publication.

Kaohsiung Medical University randomized crossover trial, currently enrolling by invitation. This trial is still enrolling and has produced no results. The reasoning behind it comes from laboratory work only. There is no evidence that this probiotic prevents polyps or bowel cancer, and it is not a replacement for colonoscopy or the follow-up your doctor recommends.

5
Antibiotic-associated diarrhea in children, 2003

Seki H et al., Pediatr Int 2003;45(1):86-90 (PMID 12654076). Children receiving antibiotics.

Clinical population described in trial publication.

Seki H et al. 2003 studied children taking antibiotics and reported fewer cases of antibiotic-associated diarrhea with C. butyricum MIYAIRI. It is a single study from more than twenty years ago, done in children, and it is the only human evidence for this use cited on the page. Results in children do not automatically apply to adults. The mucus-layer explanation comes from laboratory work, not from this study.

Side effects and drug interactions

Common Potential side effects

Generally well tolerated in the studies cited here, which were small and short; long use in Japan is reassuring but was not collected as a controlled safety study.
Mild GI upset, bloating (rare, transient).
Pregnancy: none of the studies cited on this page included pregnant women, so safety in pregnancy has not been tested here. Ask your doctor before taking any probiotic while pregnant or breastfeeding.
Long-term safety: no long-term controlled safety trial is cited on this page. What exists is decades of use in Japan under a prescription framework, which is not the same as tested long-term safety in healthy people taking it by choice.
Allergic reactions (rare).
Severely immunocompromised people, anyone with a central line, and anyone in cancer treatment should not take live-bacteria products without their doctor's approval. Live organisms can very rarely cause bloodstream infections in these groups. This applies to every probiotic, and the caution is not cancelled out by use history in Japan.
Industry involvement: the manufacturers (Miyarisan, Osel) supply the product used in this research and fund much of it. Keep that in mind when reading positive results.

Important Drug interactions

Antibiotics (fidaxomicin): one laboratory study suggested the two act together against C. difficile. This has never been tested in people, and it is not a reason to add a probiotic to treatment for a C. difficile infection on your own.
Antibiotics (general): the spore form is expected to survive alongside antibiotics better than typical Lactobacillus or Bifidobacterium products. This is based on how spores behave, not on interaction studies in people.
Most medications: no formal drug interaction studies are cited on this page, so no interaction claim can be made either way.
Immunosuppressants and cancer immunotherapy (checkpoint inhibitors such as nivolumab and ipilimumab): do not combine without your specialist's direction. The cancer trials on this page were run by oncology teams with monitoring; they are not a template for taking a probiotic alongside your own treatment.
Other probiotics: compatible.
5-FU chemotherapy: a laboratory-only idea, never tested in people. Do not add any probiotic during chemotherapy without asking your oncologist first.

Frequently asked questions about Clostridium butyricum MIYAIRI 588 (CBM588 / MIYA-BM® / Butirrisan®)

What is Clostridium butyricum MIYAIRI 588?

Clostridium butyricum Miyairi 588 (CBM588) is a butyrate-producing probiotic strain marketed as MIYA-BM® and Butirex C4 (Japan). Despite the 'Clostridium' name suggesting pathogen (C. difficile), C.

What is Clostridium butyricum MIYAIRI 588 used for?

Clostridium butyricum MIYAIRI 588 is researched primarily for Gut Health. This strain makes butyrate, a short chain fatty acid that the cells lining the colon use for energy. That sets it apart from lactic acid probiotics such as Lactobacillus and Bifidobacterium.

What is the recommended dosage of Clostridium butyricum MIYAIRI 588?

The clinically studied dose is 20-80 mg/day MIYA-BM® powder (1-4×10⁸ CFU) is the dose range cited for the Japanese product MIYA-BM, which is sold there as a prescription product. Always follow the product label and check with a healthcare provider for personal advice.

Is Clostridium butyricum MIYAIRI 588 safe, and does it have side effects?

For most healthy adults, Clostridium butyricum MIYAIRI 588 is well tolerated at studied doses. Reported effects can include: Generally well tolerated in the studies cited here, which were small and short; long use in Japan is reassuring but was not collected as a controlled safety study. Mild GI upset, bloating (rare, transient). It may also interact with some medications. Clostridium butyricum MIYAIRI 588 is not right for everyone, so check with a healthcare provider first if you are pregnant or breastfeeding, have a medical condition, or take prescription medication.

Does Clostridium butyricum MIYAIRI 588 interact with any medications?

Possible interactions include: Antibiotics (fidaxomicin): one laboratory study suggested the two act together against C. difficile. This has never been tested in people, and it is not a reason to add a probiotic to treatment for a C. difficile infection on your own. If you take prescription medication, check with a pharmacist or doctor before using it.

How strong is the scientific evidence for Clostridium butyricum MIYAIRI 588?

NutraSmarts rates the evidence for Clostridium butyricum MIYAIRI 588 as Limited (2 out of 5). It is backed by 5 clinical trials and 4 cited references summarized on this page. A higher rating reflects more, larger, and better-designed human studies.

References(4 citations)

Evidence ratings on NutraSmarts are based on the totality of human clinical research, with emphasis on randomized controlled trials, meta-analyses, and systematic reviews. The references below directly support claims made throughout this page.

  1. Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, et al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2022;28(4):704-712. doi: 10.1038/s41591-022-01694-6.PubMedUsed to support: Open-label randomized phase 1 trial, 30 patients with treatment-naive metastatic renal cell carcinoma, all receiving nivolumab plus ipilimumab. The trial missed its primary endpoint: no significant change in Bifidobacterium abundance or Shannon diversity. A progression-free survival difference (12.7 versus 2.5 months) was a secondary finding, and the response rate difference was not significant (58% versus 20%, P=0.06). The authors state that larger studies are needed to confirm the observation.
  2. Tomita Y, Ikeda T, Sakata S, Saruwatari K, Sato R, Iyama S, et al. Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer. Cancer Immunol Res. 2020;8(10):1236-1242. doi: 10.1158/2326-6066.CIR-20-0051.PubMedUsed to support: An observational study reporting an association between C. butyricum therapy and survival and response to checkpoint blockade in lung cancer patients. Because it was not a trial, it cannot show that the probiotic caused any difference; patients who take probiotics may differ from those who do not in ways that affect outcomes.
  3. Ebrahimi H, Dizman N, Meza L, Malhotra J, Li X, Dorff T, et al. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2024;30(9):2576-2585. doi: 10.1038/s41591-024-03086-4.PubMedUsed to support: A second randomized phase 1 trial, again 30 patients with metastatic renal cell carcinoma, this time on cabozantinib plus nivolumab. It missed the same primary endpoint: no change in Bifidobacterium or Shannon diversity. The higher response rate (74% versus 20%, P=0.01) was a secondary result the authors describe as a preliminary signal needing confirmation.
  4. Seki H, Shiohara M, Matsumura T, Miyagawa N, Tanaka M, Komiyama A, et al. Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI. Pediatr Int. 2003;45(1):86-90. doi: 10.1046/j.1442-200x.2003.01671.x.PubMedUsed to support: A 2003 study in children receiving antibiotics that reported less antibiotic-associated diarrhea. It is the only non-cancer human reference on this page and the only support for the diarrhea use. It was done in children, so it does not establish a dose or an effect in adults.