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© Research
Publication : Cell death and differentiation

Multifaceted modes of action of the anticancer probiotic Enterococcus hirae.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell death and differentiation - 01 Jul 2021

Goubet AG, Wheeler R, Fluckiger A, Qu B, Lemaître F, Iribarren K, Mondragón L, Tidjani Alou M, Pizzato E, Durand S, Derosa L, Aprahamian F, Bossut N, Moya-Nilges M, Derrien D, Chen G, Leduc M, Joseph A, Pons N, Le Chatelier E, Segata N, Yonekura S, Iebba V, Kepp O, Raoult D, André F, Kroemer G, Boneca IG, Zitvogel L, Daillère R,

Link to Pubmed [PMID] – 33976389

Link to DOI – 10.1038/s41418-021-00753-8

Cell Death Differ 2021 Jul; 28(7): 2276-2295

A deviated repertoire of the gut microbiome predicts resistance to cancer immunotherapy. Enterococcus hirae compensated cancer-associated dysbiosis in various tumor models. However, the mechanisms by which E. hirae restored the efficacy of cyclophosphamide administered with concomitant antibiotics remain ill defined. Here, we analyzed the multifaceted modes of action of this anticancer probiotic. Firstly, E. hirae elicited emigration of thymocytes and triggered systemic and intratumoral IFNγ-producing and CD137-expressing effector memory T cell responses. Secondly, E. hirae activated the autophagy machinery in enterocytes and mediated ATG4B-dependent anticancer effects, likely as a consequence of its ability to increase local delivery of polyamines. Thirdly, E. hirae shifted the host microbiome toward a Bifidobacteria-enriched ecosystem. In contrast to the live bacterium, its pasteurized cells or membrane vesicles were devoid of anticancer properties. These pleiotropic functions allow the design of optimal immunotherapies combining E. hirae with CD137 agonistic antibodies, spermidine, or Bifidobacterium animalis. We surmise that immunological, metabolic, epithelial, and microbial modes of action of the live E. hirae cooperate to circumvent primary resistance to therapy.

https://pubmed.ncbi.nlm.nih.gov/33976389