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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

Expression of genes involved in subcutaneous adipose tissue metabolism.GPR43, G protein-coupled receptor 43 (A). aP2, adipocyte fatty acid binding protein (B). FAS, fatty acid synthase (C). HSL, hormone-sensitive lipase (D). MGL, monoglycerol lipase (E). ZAG, zinc-a2 glycoprotein (F). CPT1a, carnitine palmitoyltransferase 1a (G). PGC1α, PPARγ coactivator 1 alpha (H). ACO, acyl-CoA oxidase (I). Data with different superscript letters are significantly different.
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pone.0131009.g005: Expression of genes involved in subcutaneous adipose tissue metabolism.GPR43, G protein-coupled receptor 43 (A). aP2, adipocyte fatty acid binding protein (B). FAS, fatty acid synthase (C). HSL, hormone-sensitive lipase (D). MGL, monoglycerol lipase (E). ZAG, zinc-a2 glycoprotein (F). CPT1a, carnitine palmitoyltransferase 1a (G). PGC1α, PPARγ coactivator 1 alpha (H). ACO, acyl-CoA oxidase (I). Data with different superscript letters are significantly different.

Mentions: We analyzed several genes controlling fatty acid synthesis or fatty acid oxidation in the subcutaneous adipose tissue (Fig 5). We observed a lower expression of the fatty acid synthase (FAS) in BaF groups versus CT group. This gene, controlled by SREBP1c, as well as those reflecting PPARγ activation (i.e., adipocyte Protein 2 (aP2), and G protein-coupled receptor 43 (GPR43)) were not affected by dietary treatments (Fig 5A–5C). Interestingly, although not reaching statistical significance, POS administration reduced the expression of the hormone sensitive lipase (HSL) induced after BaF injection without affecting the expression of the monoglycerol lipase (MGL) and the fat catabolic factor zinc-a2 glycoprotein (ZAG) (Fig 5D–5F). Importantly, PPARα dependent genes controlling β-oxidation (carnitine palmitoyltransferase 1a (CPT1a), PPARγ coactivator 1 alpha (PGC1α) and acyl-CoA oxidase (ACO)) were induced in BaF-transplanted mice and blunted in POS treated mice (Fig 5G–5I). The analysis of fatty acid profile in this adipose tissue showed a decrease in saturated fat in BaF groups, mostly palmitate (C16:0), which is in accordance with a lower de novo lipogenesis, and a decrease in oleate (C18:1) (S5 Table). A bacterial metabolite of polyunsaturated fatty acids, namely the conjugated linoleic acid trans-10, cis-12-18:2, was decreased in BaF samples, and the level was restored after INU and POS treatment.


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)

Expression of genes involved in subcutaneous adipose tissue metabolism.GPR43, G protein-coupled receptor 43 (A). aP2, adipocyte fatty acid binding protein (B). FAS, fatty acid synthase (C). HSL, hormone-sensitive lipase (D). MGL, monoglycerol lipase (E). ZAG, zinc-a2 glycoprotein (F). CPT1a, carnitine palmitoyltransferase 1a (G). PGC1α, PPARγ coactivator 1 alpha (H). ACO, acyl-CoA oxidase (I). 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.g005: Expression of genes involved in subcutaneous adipose tissue metabolism.GPR43, G protein-coupled receptor 43 (A). aP2, adipocyte fatty acid binding protein (B). FAS, fatty acid synthase (C). HSL, hormone-sensitive lipase (D). MGL, monoglycerol lipase (E). ZAG, zinc-a2 glycoprotein (F). CPT1a, carnitine palmitoyltransferase 1a (G). PGC1α, PPARγ coactivator 1 alpha (H). ACO, acyl-CoA oxidase (I). Data with different superscript letters are significantly different.
Mentions: We analyzed several genes controlling fatty acid synthesis or fatty acid oxidation in the subcutaneous adipose tissue (Fig 5). We observed a lower expression of the fatty acid synthase (FAS) in BaF groups versus CT group. This gene, controlled by SREBP1c, as well as those reflecting PPARγ activation (i.e., adipocyte Protein 2 (aP2), and G protein-coupled receptor 43 (GPR43)) were not affected by dietary treatments (Fig 5A–5C). Interestingly, although not reaching statistical significance, POS administration reduced the expression of the hormone sensitive lipase (HSL) induced after BaF injection without affecting the expression of the monoglycerol lipase (MGL) and the fat catabolic factor zinc-a2 glycoprotein (ZAG) (Fig 5D–5F). Importantly, PPARα dependent genes controlling β-oxidation (carnitine palmitoyltransferase 1a (CPT1a), PPARγ coactivator 1 alpha (PGC1α) and acyl-CoA oxidase (ACO)) were induced in BaF-transplanted mice and blunted in POS treated mice (Fig 5G–5I). The analysis of fatty acid profile in this adipose tissue showed a decrease in saturated fat in BaF groups, mostly palmitate (C16:0), which is in accordance with a lower de novo lipogenesis, and a decrease in oleate (C18:1) (S5 Table). A bacterial metabolite of polyunsaturated fatty acids, namely the conjugated linoleic acid trans-10, cis-12-18:2, was decreased in BaF samples, and the level was restored after INU and POS treatment.

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