Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia
Open accessAbstract
Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia.
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Probiotic rescue (Lactobacillus reuteri and gasseri) of inflammation and muscle/bone loss in mice proposes that gut microbiota initiate this relationship.
“probiotic rescue (Lactobacillus reuteri and gasseri) of inflammation and muscle/bone loss in mice proposes that gut microbiota initiate this relationship [19, 67, 89].”
From Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis (2018) · cites this paper as [67]
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- Authors
- Bindels, L. B., Neyrinck, A. M., Claus, S. P., Le Roy, C. I., Grangette, C., Pot, B., Martinez, I., Walter, J., Cani, P. D., & Delzenne, N. M.
- Affiliations
- UCLouvain (BE)
- University of Reading (GB)
- Department of Food and Nutritional Sciences, University of Reading , Reading, UK
- Centre National de la Recherche Scientifique (FR)
- Department of Agricultural, Food and Nutritional Science, University of Alberta , Edmonton, Alberta, Canada
- University of Alberta (CA)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Corresponding author
- Delzenne, Nathalie M
- ORCID
- Venue
- The ISME Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11-27
- Volume
- 10
- Issue
- 6
- Pages
- 1456-1470
- ISSN
- 1751-7362 (ISSN-L)
- 1751-7370
- PMC
- PMC5029183
- OpenAlex
- W2188359693
- Cited by
- 209
- References
- 58
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 19 · 2023: 26 · 2022: 27 · 2021: 27 · 2020: 18 · 2019: 20 · 2018: 18 · 2017: 15 · 2016: 5 · 2015: 1
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The ISME Journal (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CentAUR (University of Reading) (submittedVersion, cc-by-nc-sa)
- Digital Access to Libraries (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- University of Minnesota
- Fonds De La Recherche Scientifique - FNRS
- FP7 Ideas: European Research Council (336452)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Nursing › Nutrition and Dietetics › Microbial Metabolites in Food Biotechnology
- Keywords
- cancer cachexia, synbiotics, gut microbiota, acute leukemia, Lactobacillus reuteri, inulin-type fructans, Enterobacteriaceae, Parabacteroides goldsteinii, cecal microbiota, muscle atrophy, intestinal homeostasis, intestinal barrier function, intestinal immunity, survival
- MeSH terms
- Gastrointestinal Microbiome, Acute Disease, Animals, Cachexia, Colonic Neoplasms, Disease Models, Animal, Enterobacteriaceae, Female, Fructans, Homeostasis, Inflammation, Intestines, Inulin, Lactobacillus, Leukemia, Mice, Inbred BALB C, Bacteroidetes, Cell Proliferation, Mice, Metabolomics, Synbiotics
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