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

Bindels LB, Neyrinck AM, Salazar N, Taminiau B, Druart C, Muccioli GG, François E, Blecker C, Richel A, Daube G, Mahillon J, de los Reyes-Gavilán CG, Cani PD, Delzenne NM - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus

Changes in microbial diversity and populations in the caecal content, assessed by 454-pyrosequencing.Microbial diversity indexes (A). Principal component analysis based on the relative abundance distribution at the species level (B). Relative abundances of bacterial taxa accounting for more than 1%, at the phylum, family and genus levels (C). Relative abundances of the Bacteroidetes phylum, Bacteroidaceae family, Bacteroides genus and species-like Bacteroides HQ788586 (D). Data with different superscript letters are significantly different.
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pone.0131009.g001: Changes in microbial diversity and populations in the caecal content, assessed by 454-pyrosequencing.Microbial diversity indexes (A). Principal component analysis based on the relative abundance distribution at the species level (B). Relative abundances of bacterial taxa accounting for more than 1%, at the phylum, family and genus levels (C). Relative abundances of the Bacteroidetes phylum, Bacteroidaceae family, Bacteroides genus and species-like Bacteroides HQ788586 (D). Data with different superscript letters are significantly different.

Mentions: The BaF-POS mice exhibited a decreased caecal microbial diversity compared to the BaF mice (Fig 1A). The differences within the intestinal microbial ecosystem between the treatment groups were first assessed by principal component analysis (PCA) of the relative abundances at the genus level (Fig 1B) and 38% of the total variation was explained by the first PCA axis. Indeed, a distinct cluster was observed for mice receiving POS supplementation. To assess specific changes in intestinal microbiota, we compared the relative abundance of bacterial taxa between treatment groups (Fig 1C and S3 Table). We observed a significant phylum-wide shift from Firmicutes to Bacteroidetes upon POS supplementation. At the family level, the abundance of Desulfovibrioceae significantly decreased in BaF mice vs CT mice. This effect was even more pronounced under POS or INU supplementation. Several important changes were observed only after POS supplementation such as a decrease in Ruminococaceae and S24-7 families and in contrast a 31- and 9-fold increase in Prevotellaceae and Bacteroidaceae, respectively, two major families belonging to Bacteroidetes phylum. At a lower taxonomic level, the most prominent difference was obtained with POS supplementation inducing a huge increase in Bacteroides genus (reaching more than 20% of abundance). In contrast, INU supplementation led to a 2-fold decrease in Alistipes spp. belonging to the Rikenellaceae family. Finally, we determined that the most prominent increase at the OTU level after POS treatment corresponded to Bacteroides HQ788586 that gave 99% homology with B. dorei. This 20-fold increase of B. dorei impacts on the relative abundances of the genus, family and phylum to which this microbe belongs (Fig 1D).


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

Bindels LB, Neyrinck AM, Salazar N, Taminiau B, Druart C, Muccioli GG, François E, Blecker C, Richel A, Daube G, Mahillon J, de los Reyes-Gavilán CG, Cani PD, Delzenne NM - PLoS ONE (2015)

Changes in microbial diversity and populations in the caecal content, assessed by 454-pyrosequencing.Microbial diversity indexes (A). Principal component analysis based on the relative abundance distribution at the species level (B). Relative abundances of bacterial taxa accounting for more than 1%, at the phylum, family and genus levels (C). Relative abundances of the Bacteroidetes phylum, Bacteroidaceae family, Bacteroides genus and species-like Bacteroides HQ788586 (D). Data with different superscript letters are significantly different.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476728&req=5

pone.0131009.g001: Changes in microbial diversity and populations in the caecal content, assessed by 454-pyrosequencing.Microbial diversity indexes (A). Principal component analysis based on the relative abundance distribution at the species level (B). Relative abundances of bacterial taxa accounting for more than 1%, at the phylum, family and genus levels (C). Relative abundances of the Bacteroidetes phylum, Bacteroidaceae family, Bacteroides genus and species-like Bacteroides HQ788586 (D). Data with different superscript letters are significantly different.
Mentions: The BaF-POS mice exhibited a decreased caecal microbial diversity compared to the BaF mice (Fig 1A). The differences within the intestinal microbial ecosystem between the treatment groups were first assessed by principal component analysis (PCA) of the relative abundances at the genus level (Fig 1B) and 38% of the total variation was explained by the first PCA axis. Indeed, a distinct cluster was observed for mice receiving POS supplementation. To assess specific changes in intestinal microbiota, we compared the relative abundance of bacterial taxa between treatment groups (Fig 1C and S3 Table). We observed a significant phylum-wide shift from Firmicutes to Bacteroidetes upon POS supplementation. At the family level, the abundance of Desulfovibrioceae significantly decreased in BaF mice vs CT mice. This effect was even more pronounced under POS or INU supplementation. Several important changes were observed only after POS supplementation such as a decrease in Ruminococaceae and S24-7 families and in contrast a 31- and 9-fold increase in Prevotellaceae and Bacteroidaceae, respectively, two major families belonging to Bacteroidetes phylum. At a lower taxonomic level, the most prominent difference was obtained with POS supplementation inducing a huge increase in Bacteroides genus (reaching more than 20% of abundance). In contrast, INU supplementation led to a 2-fold decrease in Alistipes spp. belonging to the Rikenellaceae family. Finally, we determined that the most prominent increase at the OTU level after POS treatment corresponded to Bacteroides HQ788586 that gave 99% homology with B. dorei. This 20-fold increase of B. dorei impacts on the relative abundances of the genus, family and phylum to which this microbe belongs (Fig 1D).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.

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.

No MeSH data available.


Related in: MedlinePlus