Benefits
C. difficile colonization resistance via metabolic + immune modulation (Nature Sci Rep 2021)
Nature Scientific Reports 2021 — CBM 588 ENHANCES COLONIZATION RESISTANCE against C. difficile via METABOLIC + IMMUNE MODULATION. RESULTS: ENHANCED ANTIBACTERIAL ACTIVITY OF FIDAXOMICIN against C. difficile + NEGATIVELY MODULATED gut SUCCINATE levels (preventing C. difficile proliferation) + DOWNREGULATED TNF-α-PRODUCING MACROPHAGES in colon lamina propria + UPREGULATED T cell-dependent pathogen-specific IgA via IL-17A-producing CD4+ cells + plasma B cells + Th17 cells enhancing gut epithelial barrier function. Foundational mechanism evidence for C. difficile prophylaxis.
IBS-D (PROREDI 8-week RCT NCT06676514)
NCT06676514 PROREDI (PRObiotic REmedy for DIarrhea) — clinical trial sponsored by Liaquat University of Medical & Health Sciences. Population: IBS-D (Diarrhea-predominant) patients. Intervention: probiotic Butirrisan® (CBM588) 3 tablets daily for 8 weeks vs standard of care (Trimebutine maleate + lactose-free no-slag diet). STATUS: COMPLETED. Outcomes: gut microbiota balance + IBS-D symptom improvement + intestinal integrity. Important emerging Caucasian-population evidence (Pakistan) — broadens beyond traditional Asian clinical use.
Colorectal adenomatous polyp recurrence (NCT06855355 EMERGING)
NCT06855355 — RANDOMIZED CROSSOVER TRIAL (Kaohsiung Medical University). STATUS: ENROLLING_BY_INVITATION. Population: adult patients with history of colorectal polyps. Intervention: CBM588 vs control. Mechanism: butyrate-producing probiotic with anti-inflammatory + anti-tumorigenic effects via HDAC inhibition + apoptosis induction + Treg differentiation + ONCOGENIC MYC DESTABILIZATION + thymidylate synthase downregulation (5-FU sensitivity enhancement). Important emerging colorectal cancer prevention evidence.
Antibiotic-associated diarrhea prevention pediatric (Seki 2003)
Seki et al. 2003 — preventive effect of CBM 588 for ANTIBIOTIC-ASSOCIATED DIARRHEA (AAD) in CHILDREN. Mechanism: CBM 588 protects gut MUCIN LAYER from antibiotic-induced dysbiosis + promotes mucin production via gut microbiota modulation. Important pediatric AAD evidence + foundational mechanism (mucin protection).
C. difficile inhibitory interaction in vitro (PMID 21700738)
PMID 21700738 — inhibitory interaction between Japanese probiotic strain CBM588 and hospital pathogen C. DIFFICILE in vitro. RESULTS: TOXICITY of C. difficile REDUCED by CBM588. Mechanism: direct interaction reducing C. difficile virulence (toxin production). Foundational in vitro mechanism supporting clinical AAD/CDI applications.
Antibiotic-induced dysbiosis gut microbiome shift (PMC8962260)
PMC6970176 mouse antibiotic-induced dysbiosis — CBM 588 INCREASED ABUNDANCE of BIFIDOBACTERIUM, LACTOBACILLUS, LACTOCOCCUS species + ENHANCED INTESTINAL BARRIER FUNCTION. Mechanism: cross-feeding effects on commensal microbiome via butyrate production + microbiome diversity restoration. Important mechanism for post-antibiotic recovery.
Japanese pharmaceutical use 50+ years (regulatory milestone)
CBM 588 approved for clinical use in humans by JAPANESE GOVERNMENT in 1963 (Miyarisan Pharmaceutical). 50+ years clinical use record in Japan. Variously classed as PHARMACEUTICAL DRUG, QUASI-DRUG, OTC PROBIOTIC. Used in SEVERELY-ILL, IMMUNOCOMPROMISED, HOSPITALIZED PATIENTS, PREGNANT WOMEN — extensive safety record. Foundational regulatory + clinical use distinction among probiotics.
Mechanism of action
Butyrate production (DISTINGUISHING)
CBM588 is BUTYRATE-PRODUCING — colonocyte primary energy source (60-70%), HDAC inhibition, anti-inflammatory + anti-carcinogenic effects. Distinguishing from typical Lactobacillus/Bifidobacterium probiotics. Foundational metabolite mechanism.
Spore formation + heat/acid resistance
Spore-forming gram-positive obligate anaerobic Bacillus. Spore-form survives gastric acidity + heat. Mechanism: efficient delivery to lower GI without enteric coating. Practical pharmaceutical advantage.
C. difficile direct inhibition (Sci Rep 2021 + PMID 21700738)
DIRECT inhibition of C. difficile growth + virulence. Mechanism: reduced succinate (preventing C. difficile proliferation) + direct interaction reducing C. difficile toxicity + ENHANCED FIDAXOMICIN antibacterial activity. Foundation antimicrobial mechanism.
Mucin layer protection + production
Seki 2003 + multiple subsequent — CBM 588 PROTECTS gut MUCIN LAYER from antibiotic-induced dysbiosis + PROMOTES mucin production via microbiota modulation. Mechanism: mucosal protection particularly relevant for AAD prevention.
TNF-α macrophage downregulation + IgA upregulation (Sci Rep 2021)
DOWNREGULATES TNF-α-producing macrophages in colon lamina propria + UPREGULATES T cell-dependent pathogen-specific IgA via IL-17A-producing CD4+ cells + plasma B cells. Mechanism: anti-inflammatory + adaptive immunity enhancement.
Th17 enhancement + gut barrier function
Sci Rep 2021 — Th17 cells in colon lamina propria ENHANCED gut epithelial BARRIER FUNCTION. Mechanism: T helper 17 cell-mediated mucosal immunity supporting barrier integrity.
Bifidobacterium + Lactobacillus + Lactococcus enhancement
PMC6970176 — CBM 588 increases abundance of beneficial commensals (Bifidobacterium, Lactobacillus, Lactococcus). Mechanism: cross-feeding via butyrate production + niche modification. Microbiome restoration after antibiotic dysbiosis.
Oncogenic MYC destabilization (CRC prevention)
PMC12712693 (CBM588 colorectal polyp recurrence rationale) — destabilizes MYC transcription factor involved in CRC progression + downregulates thymidylate synthase (enhancing 5-FU chemo sensitivity). Mechanism: anti-tumorigenic effects in colorectal cancer context.
Clinical trials
Mechanism study (Nature Scientific Reports 2021, doi:10.1038/s41598-021-94572-z, PMC8323641).
Mouse model + cellular studies. CBM 588 administration with/without C. difficile infection + fidaxomicin antibiotic.
ENHANCED ANTIBACTERIAL ACTIVITY of FIDAXOMICIN against C. difficile + NEGATIVELY MODULATED gut SUCCINATE levels (preventing C. difficile proliferation) + DOWNREGULATED TNF-α-producing macrophages in colon lamina propria + UPREGULATED T cell-dependent pathogen-specific IgA via IL-17A-producing CD4+ cells + plasma B cells. Th17 cells enhanced gut epithelial barrier function. Foundational mechanism evidence for C. difficile colonization resistance.
Non-randomized parallel cohort interventional study (NCT06676514 PROREDI). Sponsor: Liaquat University of Medical & Health Sciences. Status: COMPLETED.
Adult patients with IBS-D (Diarrhea-predominant). Probiotic Butirrisan® (CBM588) 3 tablets daily for 8 weeks vs standard of care (Trimebutine maleate + lactose-free no-slag diet).
STATUS: COMPLETED. Outcomes: gut microbiota balance + IBS-D symptom improvement + intestinal integrity. Important emerging Caucasian-population (Pakistan) evidence broadening beyond traditional Asian clinical use. Real-world clinical setting design.
Phase 2 randomized double-blind quadruple-masked placebo-controlled trial (NCT01077245). Sponsor: Osel Inc.
200 patients with confirmed C. difficile infection (CDI) treated with metronidazole or vancomycin. MIYA-BM Fine Granules (CBM588) 2 g/dose orally twice daily for 42 days vs placebo. Follow-up 180 days.
STATUS: WITHDRAWN due to LACK OF ENROLLMENT (NOT efficacy or safety concerns). Important honest framing: phase 2 RCT did not complete enrollment in US population — Japanese clinical use record remains primary evidence base for CBM588. Highlights translational challenges between Japanese established use + US clinical trial requirements.
About this ingredient
CLOSTRIDIUM BUTYRICUM MIYAIRI 588 (CBM588) is a JAPANESE PHARMACEUTICAL/QUASI-DRUG/OTC PROBIOTIC isolated by DR. CHIKAJI MIYAIRI from feces in 1933 + CBM 588 specifically isolated from soil in Nagano in 1963. Used 50+ YEARS in JAPAN for diarrhea + AAD + C. difficile prophylaxis. Brand names: MIYA-BM® Fine Granules (Miyarisan/Osel) + BUTIRRISAN®. APPROVED for clinical use in humans by Japanese government 1963. Variously classed as PHARMACEUTICAL DRUG, QUASI-DRUG, OTC PROBIOTIC. Extensive use in SEVERELY-ILL, IMMUNOCOMPROMISED, HOSPITALIZED PATIENTS, PREGNANT WOMEN — distinguishing safety record. PIVOTAL CLINICAL EVIDENCE: NATURE SCIENTIFIC REPORTS 2021 (doi:10.1038/s41598-021-94572-z) — CBM 588 ENHANCES C. DIFFICILE COLONIZATION RESISTANCE via metabolic + immune modulation: ENHANCED FIDAXOMICIN antibacterial activity + NEGATIVELY MODULATED gut SUCCINATE levels (prevents C. difficile proliferation) + DOWNREGULATED TNF-α macrophages in colon lamina propria + UPREGULATED IgA via IL-17A CD4+ + plasma B cells + Th17 enhanced gut epithelial barrier function. NCT06676514 PROREDI IBS-D 8-WEEK RCT (Liaquat University Pakistan, COMPLETED) — Butirrisan® 3 tablets daily for 8 weeks vs standard of care (Trimebutine + lactose-free no-slag diet). NCT06855355 COLORECTAL ADENOMATOUS POLYP recurrence randomized crossover (Kaohsiung Medical University, ENROLLING_BY_INVITATION) — anti-tumorigenic mechanism via HDAC inhibition + Treg differentiation + MYC destabilization + thymidylate synthase downregulation. NCT01077245 MIYA-BM CDI recurrence phase 2 RCT (Osel Inc) WITHDRAWN due to LACK OF ENROLLMENT (not efficacy concerns) — important honest framing of Japanese-vs-US translational challenges. SEKI 2003 — pediatric AAD prevention via mucin layer protection + production. PMID 21700738 — in vitro inhibitory interaction reducing C. difficile toxicity. PMC8962260 review — gut microbiome shift (Bifidobacterium, Lactobacillus, Lactococcus enhancement). PMC6970176 — antibiotic-induced dysbiosis mouse model showing barrier function enhancement.
MECHANISMS: BUTYRATE PRODUCTION (DISTINGUISHING — colonocyte primary energy 60-70%, HDAC inhibition, anti-inflammatory + anti-carcinogenic); SPORE FORMATION + heat/acid resistance; C. DIFFICILE DIRECT INHIBITION (Sci Rep 2021 + PMID 21700738 — succinate modulation + fidaxomicin enhancement + toxicity reduction); MUCIN LAYER PROTECTION + PRODUCTION (Seki 2003 mechanism); TNF-α MACROPHAGE DOWNREGULATION + IgA UPREGULATION (Sci Rep 2021); Th17 ENHANCEMENT + gut barrier function; BIFIDOBACTERIUM + LACTOBACILLUS + LACTOCOCCUS enhancement (cross-feeding); ONCOGENIC MYC DESTABILIZATION + thymidylate synthase downregulation (CRC prevention rationale). EVIDENCE: 4/5 reflects: (1) NATURE SCIENTIFIC REPORTS 2021 PIVOTAL MECHANISM evidence — multi-modal C. difficile colonization resistance with fidaxomicin synergy, (2) NCT06676514 PROREDI 8-WEEK IBS-D RCT (COMPLETED) — emerging Caucasian-population evidence, (3) NCT06855355 COLORECTAL POLYP RECURRENCE crossover trial (ENROLLING — emerging cancer prevention), (4) SEKI 2003 PEDIATRIC AAD prevention foundational evidence, (5) PMID 21700738 IN VITRO C. DIFFICILE INHIBITION mechanism, (6) WELL-CHARACTERIZED butyrate production + multi-mechanism action, (7) JAPANESE PHARMACEUTICAL APPROVAL 1963 + 50+ YEAR CLINICAL USE RECORD (REGULATORY MILESTONE rare among probiotics), (8) HONEST FRAMING — NCT01077245 phase 2 CDI RCT WITHDRAWN due to lack of enrollment (translational challenge between Japanese established use + US RCT requirements), (9) USE IN PREGNANT WOMEN + IMMUNOCOMPROMISED + SEVERELY-ILL patients (distinguishing safety record), (10) higher-evidence than typical probiotic supplement due to Japanese pharmaceutical/quasi-drug regulatory status + 50+ year clinical use + recent Sci Rep 2021 mechanism evidence + multiple emerging RCTs. SAFETY: Excellent — 50+ year Japanese clinical use record + use in pregnant women + immunocompromised + hospitalized patients. Best positioned as: (a) C. DIFFICILE PROPHYLAXIS in hospitalized antibiotic-treated patients (Japanese standard of care; Sci Rep 2021 mechanism evidence), (b) ANTIBIOTIC-ASSOCIATED DIARRHEA PREVENTION (Seki 2003 pediatric evidence + 50+ year Japanese use), (c) IBS-D SYMPTOM management (NCT06676514 PROREDI emerging evidence), (d) COLORECTAL CANCER PREVENTION (NCT06855355 emerging — anti-tumorigenic mechanism), (e) FIDAXOMICIN ADJUNCT for CDI (Sci Rep 2021 synergy evidence), (f) GUT BARRIER + MUCIN PROTECTION (multi-mechanism evidence), (g) PREGNANCY: USED SAFELY in Japan — distinguishing safety record, (h) IMMUNOCOMPROMISED: extensive Japanese clinical experience supportive, (i) PEDIATRIC: established Japanese use, (j) MIYA-BM® / BUTIRRISAN® branded preparations preferable for clinical evidence-matched formulation, (k) higher-evidence than typical probiotic supplement due to Japanese pharmaceutical regulatory status + 50+ year clinical use record. Honest framing: CBM588 is one of the BEST-EVIDENCED probiotics in pharmaceutical context — 50+ year Japanese clinical use + 1963 government approval + use in pregnant women + immunocompromised + hospitalized patients is genuinely distinguishing regulatory + clinical pedigree. Sci Rep 2021 mechanism evidence (C. difficile colonization resistance + fidaxomicin synergy + IgA + Th17) is methodologically rigorous + clinically relevant. NCT01077245 phase 2 US CDI RCT WITHDRAWAL due to lack of enrollment is honest evidence-quality limitation — Japanese established use + US RCT requirements have translational challenge but doesn't reflect efficacy/safety concerns. Butyrate-producing distinguishing mechanism positions CBM588 differently from Lactobacillus/Bifidobacterium probiotics. Recent NCT06676514 PROREDI IBS-D + NCT06855355 colorectal polyp recurrence trials extend evidence beyond Japanese context. Reasonable C. difficile prophylaxis + AAD prevention + IBS-D + emerging colorectal cancer prevention adjunct based on rigorous Japanese clinical record + recent mechanism evidence — particularly compelling for hospitalized patients on antibiotics or those with recurrent C. difficile risk.