Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss

Sarah A Pötgens; Sophie Lecop; Violaine Havelange; Fuyong Li; Audrey M Neyrinck; Nathalie Neveux; Johan Maertens; Jens Walter; Hélène Schoemans; Nathalie M Delzenne; Laure B Bindels

doi:10.1016/j.clnu.2023.09.021

Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss

Clin Nutr. 2023 Nov;42(11):2214-2228. doi: 10.1016/j.clnu.2023.09.021. Epub 2023 Sep 25.

Authors

Affiliations

¹ Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
² Department of Hematology, Cliniques Universitaires Saint-Luc, UCLouvain, Université catholique de Louvain, Brussels, Belgium; Experimental Medicine Unit, De Duve Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
³ Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
⁴ Clinical Chemistry Department, Cochin Hospital, Paris Centre University Hospitals, Paris, France.
⁵ Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
⁶ Department of Medicine, School of Microbiology, APC Microbiome Ireland, University College Cork, Cork, Ireland.
⁷ Department of Hematology, University Hospitals Leuven, Leuven, Belgium; Department of Public Health and Primary Care, ACCENT VV, KU Leuven - University of Leuven, Leuven, Belgium.
⁸ Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium; Welbio Department, WEL Research Institute, Wavre, Belgium. Electronic address: laure.bindels@uclouvain.be.

PMID: 37806074
DOI: 10.1016/j.clnu.2023.09.021

Abstract

Background & aims: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.

Methods: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed.

Results: AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets.

Conclusion: AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss.

Trial registration: NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.

Keywords: Anorexia; Antibiotics; Cachexia; Chemotherapy; Gut permeability; Microbiome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cachexia
Gastrointestinal Microbiome* / physiology
Humans
Leukemia, Myeloid, Acute* / drug therapy
Metabolomics
Weight Loss

Associated data

ClinicalTrials.gov/NCT03881826