1. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients
- Author
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Xavier Thomas, Lilia Boucinha, Christian Recher, Anne-Sophie Michallet, Sophie Ducastelle-Lepretre, Mauricette Michallet, Stéphanie Nguyen, Clément Rocher, Pierre Peterlin, Etienne Paubelle, Florent Malard, Suzanne Tavitian, Colombe Saillard, Marie-Virginie Larcher, Sarah Bertoli, Evelyne D'incan-Corda, Ollivier Legrand, Patrice Chevallier, Emilie Plantamura, Joël Doré, Anne Vekhoff, Simona Lapusan, Jerome Rey, Lila Gilis, Mohamad Mohty, Cyrielle Gasc, Françoise Isnard, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), MaaT Pharma [Lyon], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 788191,Homo.symbiosus, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Antibiotics ,General Physics and Astronomy ,Gut flora ,Feces ,0302 clinical medicine ,fluids and secretions ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,Prospective Studies ,education.field_of_study ,Multidisciplinary ,biology ,Myeloid leukemia ,Fecal Microbiota Transplantation ,Middle Aged ,Anti-Bacterial Agents ,3. Good health ,Leukemia ,Treatment Outcome ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Adult ,medicine.drug_class ,Science ,Population ,Transplantation, Autologous ,digestive system ,Article ,Phase II trials ,Acute myeloid leukaemia ,General Biochemistry, Genetics and Molecular Biology ,Young Adult ,03 medical and health sciences ,medicine ,Humans ,education ,Aged ,Bacteria ,business.industry ,Induction chemotherapy ,General Chemistry ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,Transplantation ,030104 developmental biology ,Immunology ,Dysbiosis ,business - Abstract
Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level., The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.
- Published
- 2021