Akkermansia muciniphila

Higher pre-treatment stool abundance of A. muciniphila was significantly associated with clinical response and longer progression-free survival in NSCLC and RCC patients receiving PD-1/PD-L1 blockade; A. muciniphila was detectable in 69% (11/16) of partial responders vs. 34% (15/44) of progressors (P=0.007) in the discovery metagenomics cohort (n=100), with findings replicated in two independent validation cohorts (n=53 NSCLC+RCC and n=239 NSCLC).

PMID: 29097494

D002289 Carcinoma, Non-Small-Cell Lung D002292 Carcinoma, Renal Cell D000082082 Immune Checkpoint Inhibitors H00014 Non-small cell lung cancer H00021 Renal cell carcinoma

Antibiotic use (β-lactams, fluoroquinolones, or macrolides) within 2 months before or 1 month after initiation of PD-1/PD-L1 mAb was independently associated with significantly shorter progression-free survival and overall survival in 249 patients with NSCLC, RCC, and urothelial carcinoma (median OS: 15.3 vs. 8.3 months; P<0.001), confirmed in 239 additional NSCLC patients, implicating antibiotic-mediated gut dysbiosis — including depletion of A. muciniphila — as a driver of primary ICI resistance.

PMID: 29097494

D000900 Anti-Bacterial Agents D002289 Carcinoma, Non-Small-Cell Lung D000082082 Immune Checkpoint Inhibitors H00022 Bladder cancer H00014 Non-small cell lung cancer H00021 Renal cell carcinoma

Akkermansia muciniphila was among organisms enriched in responders (objective response or stable disease >12 months) to FMT plus pembrolizumab in a Phase 2 trial of 15 PD-1-refractory advanced melanoma patients; transkingdom network analysis identified it as negatively correlated with circulating CXCL8 (IL-8), an immunosuppressive cytokine elevated in non-responders and associated with immune checkpoint blockade resistance.

PMID: 33542131

D008545 Melanoma H00038 Melanoma

Akkermansia muciniphila was enriched in the gut microbiome of non-responders to cancer therapeutics (immune checkpoint blockade, platinum-based chemotherapy, EGFR TKI) compared with responders among patients with advanced NSCLC (stage IIIB/IV), identified by LEfSe analysis of 16S rRNA gut metagenomics; the authors note that immunomodulatory effects of gut microbiota on cancer therapy may differ by cancer type, race, and geography.

PMID: 33432149

D002289 Carcinoma, Non-Small-Cell Lung D000082082 Immune Checkpoint Inhibitors H00014 Non-small cell lung cancer

Akkermansia muciniphila displays intrinsic resistance to glycopeptide antibiotics, indicating that antimicrobial resistance profiles of novel probiotic organisms may have clinical implications for gut microbiota management in susceptible patient populations.

PMID: 40544256

Fecal microbiota transplantation from ICI-responding NSCLC/RCC patients into germ-free or antibiotic-treated mice conferred sensitivity to PD-1 blockade, increasing CXCR3+CD4+ tumor-infiltrating lymphocytes and PD-L1 expression on splenic T cells; FMT from non-responders conveyed resistance to PD-1 blockade, establishing a causal role for gut microbiome composition — including A. muciniphila — in determining ICI efficacy.

PMID: 29097494

D000069467 Fecal Microbiota Transplantation D009369 Neoplasms

Oral supplementation with A. muciniphila in antibiotic-dysbiotic mice restored PD-1 blockade antitumor efficacy against RET melanoma, MCA-205 sarcoma, and orthotopic LLC lung cancers in an IL-12-dependent manner, increasing CCR9+CXCR3+CD4+ central memory T cell recruitment into mesenteric lymph nodes and tumor beds, and elevating intratumoral CD4+/FoxP3+ ratios.

PMID: 29097494

D000082082 Immune Checkpoint Inhibitors D009369 Neoplasms