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Patients with B-cell lymphoma treated with CD19 CAR T cells exhibited profound intestinal dysbiosis, exacerbated after CAR T-cell infusion. This dysbiosis was characterized by low bacterial richness, low soluble MAdCAM-1, and loss of Akkermansia species, associated with resistance to therapy. Mechanistically, oral Akkermansia massiliensis supplementation increased CAR T-cell infiltration into the bone marrow, inverted the CD4\/CD8 CAR T-cell ratio, favored Tc1 CD8+ T-cell polarization, and promoted the release of tryptophan-derived indole metabolites, leading to better tumor control. The clinical benefit of Akkermansia spp. supplementation was abolished when CAR T cells were genetically deficient in the indole receptor, aryl hydrocarbon receptor (AhR). AhR-agonistic indoles alone failed to replicate the bacterium\u2019s anticancer effects. These findings suggest that Akkermansia supplementation could improve CAR T-cell potency in patients with intestinal Akkermansia deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>B-cell lymphoma patients treated with CAR T cells harbor major gut microbiota perturbations and related metabolism that restrain CAR T-cell therapy. Reprogramming the gut microbiota ecosystem by oral A. massiliensis supplementation induces CAR T-cell niching and Tc1 differentiation in the bone marrow, promoting tumor control in an AhR-dependent manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-1230","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T15:11:43Z","timestamp":1749654703000},"page":"1905-1926","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Gut Microbiota Modulation through\n                    <i>Akkermansia<\/i>\n                    spp\n                    <i>.<\/i>\n                    Supplementation Increases CAR T-cell Potency"],"prefix":"10.1158","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6866-5300","authenticated-orcid":false,"given":"Laura","family":"Marcos-Kovandzic","sequence":"first","affiliation":[{"name":"1Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris-Saclay, Le Kremlin-Bic\u00eatre, France."},{"name":"2Gustave Roussy Cancer Campus (GRCC), Clinicobiome, Villejuif, France."},{"name":"3Institut National de la Sant\u00e9 Et de la Recherche Medicale (INSERM) U1015, Institut Gustave Roussy, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1272-4119","authenticated-orcid":false,"given":"Michele","family":"Avagliano","sequence":"additional","affiliation":[{"name":"4Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4290-4262","authenticated-orcid":false,"given":"Myriam","family":"Ben Khelil","sequence":"additional","affiliation":[{"name":"3Institut National de la Sant\u00e9 Et de la Recherche Medicale (INSERM) U1015, Institut Gustave Roussy, Villejuif, France."},{"name":"5Hematology Department, Institut Gustave Roussy, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7588-7432","authenticated-orcid":false,"given":"Janesa","family":"Srikanthan","sequence":"additional","affiliation":[{"name":"3Institut National de la Sant\u00e9 Et de la Recherche Medicale (INSERM) U1015, Institut Gustave Roussy, Villejuif, France."},{"name":"5Hematology Department, Institut Gustave Roussy, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-5554","authenticated-orcid":false,"given":"Rim","family":"Abdallah","sequence":"additional","affiliation":[{"name":"3Institut National de la Sant\u00e9 Et de la Recherche Medicale (INSERM) U1015, Institut Gustave Roussy, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8066-870X","authenticated-orcid":false,"given":"Valentina","family":"Petrocelli","sequence":"additional","affiliation":[{"name":"6IFOM ETS, The AIRC Institute of Molecular Oncology, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6372-4075","authenticated-orcid":false,"given":"Jessica","family":"Rengassamy","sequence":"additional","affiliation":[{"name":"3Institut National de la Sant\u00e9 Et de la Recherche Medicale (INSERM) U1015, Institut Gustave Roussy, Villejuif, France."},{"name":"5Hematology Department, Institut Gustave Roussy, Villejuif, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1802-5103","authenticated-orcid":false,"given":"Alexia","family":"Alfaro","sequence":"additional","affiliation":[{"name":"7Gustave Roussy, UMS AMMICa, CNRS UAR3655, INSERM US23, 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