Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemia mice with cachexia

Bindels, L. B., Neyrinck, A. M., Claus, S. P., Le Roy, C. I., Grangette, C., Pot, B., Martinez, I., Walter, J., Cani, P. D. and Delzenne, N. M. (2016) Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemia mice with cachexia. ISME Journal, 10 (6). pp. 1456-1470. ISSN 1751-7370 doi: 10.1038/ismej.2015.209

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/38532
Identification Number/DOI	10.1038/ismej.2015.209
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > NMR (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Food Microbial Sciences Research Group
Publisher	Nature Publishing Group
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