Non Digestible Oligosaccharides Modulate the Gut Microbiota to Control the Development of Leukemia and Associated Cachexia in Mice

We tested the hypothesis that changing the gut microbiota using pectic oligosaccharides (POS) or inulin (INU) differently modulates the progression of leukemia and related metabolic disorders. Mice were transplanted with Bcr-Abl-transfected proB lymphocytes mimicking leukemia and received either POS or INU in their diet (5%) for 2 weeks. Combination of pyrosequencing, PCR-DGGE and qPCR analyses of the 16S rRNA gene revealed that POS decreased microbial diversity and richness of caecal microbiota whereas it increased Bifidobacterium spp., Roseburia spp. and Bacteroides spp. (affecting specifically B. dorei) to a higher extent than INU. INU supplementation increased the portal SCFA propionate and butyrate, and decreased cancer cell invasion in the liver. POS treatment did not affect hepatic cancer cell invasion, but was more efficient than INU to decrease the metabolic alterations. Indeed, POS better than INU delayed anorexia linked to cancer progression. In addition, POS treatment increased acetate in the caecal content, changed the fatty acid profile inside adipose tissue and counteracted the induction of markers controlling β-oxidation, thereby hampering fat mass loss. Non digestible carbohydrates with prebiotic properties may constitute a new nutritional strategy to modulate gut microbiota with positive consequences on cancer progression and associated cachexia. © 2015 Bindels et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
LBB is a Postdoctoral Researcher from the F.R.S.-FNRS (Fond National de la Recherche Scientifique, Belgium). NS is the recipient of a postdoctoral fellowship from the Spanish Ministry of Education, Culture and Sports. CD benefits from a Danone Institute grant. PDC is a research associate at FRS-FNRS (Fonds de la Recherche Scientifique, Belgium). GGM is a recipient of grants from FRS-FNRS and from FSR (UCL, Belgium). Financial support has been provided by a grant from the Walloon Region (Hydrasanté Project, convention 816875) and by a grant from the Spanish Ministry of Economy and Competitiveness (AGL2010-16525). NMD and PDC are recipients of grants from FNRS, and PDC is a recipient of ERC Starting Grant 2013 (European Research Council, Starting Grant 336452-ENIGMO). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.