Back to Search
Start Over
Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening
- Source :
- Gut Microbes, Vol 12, Iss 1 (2020), Gut microbes, Gut microbes, 2020, 12 (1), pp.1800897. ⟨10.1080/19490976.2020.1800897⟩, Gut microbes, Taylor & Francis, 2020, 12 (1), pp.1800897. ⟨10.1080/19490976.2020.1800897⟩, Gut Microbes, article-version (VoR) Version of Record
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis Group, 2020.
-
Abstract
- International audience; Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except forEscherichia coliandEnterococcusspp., which became dominant. Both the alpha and beta-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase ofE. coliandEnterococcusspp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved alpha-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients' outcome.
- Subjects :
- Adult
Male
[SDV]Life Sciences [q-bio]
Mice, Transgenic
chemotherapy
Feces
Mice
mucus
Antineoplastic Combined Chemotherapy Protocols
microbiota
Animals
Humans
acute leukemia
Intestinal Mucosa
lcsh:RC799-869
Aged
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Induction Chemotherapy
Middle Aged
Fatty Acids, Volatile
Gastrointestinal Microbiome
[SDV] Life Sciences [q-bio]
Leukemia, Myeloid, Acute
intestinal barrier
Dysbiosis
Female
lcsh:Diseases of the digestive system. Gastroenterology
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Research Article
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19490984 and 19490976
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Gut Microbes
- Accession number :
- edsair.pmid.dedup....17d7e9d975da1c3cd44c8d43a912bfd8