Abstract

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.

Highlights

  • Over the past decade, gut microbiota has appeared as a fully-fledged component involved in host energy homeostasis

  • There is a clear need to test the effectiveness of potential probiotics and prebiotics in this context [28]

  • We assessed for the first time the effect of sugar beet pectic oligosaccharides (POS) on gut microbiota composition and function in vivo, in a mouse model of leukemia

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Summary

Introduction

Gut microbiota has appeared as a fully-fledged component involved in host energy homeostasis. Recent studies have highlighted that changes in gut microbial ecosystem are associated with specific diseases and life steps, such as inflammatory bowel diseases, obesity, diabetes, autism, pregnancy and ageing [1, 2]. Developing tools able to influence the composition and metabolic activity of the gut microbiota—such as prebiotics—might lead to innovative therapeutic approaches. We have recently proposed to define prebiotics as nondigestible compounds that, through its metabolization by microorganisms in the gut, modulates composition and/or activity of the gut microbiota, conferring a beneficial physiological effect on the host [3]. New prebiotic compounds arouse a high therapeutic interest because different prebiotics could differentially impact the gut microbial ecosystem, thereby leading to specific health benefits in pathological contexts

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