Author
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HAMILTON, KRISTINA - University Of California |
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RONVEAUX, CHARLOTTE - University Of California |
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RUST, BRET - University Of California |
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Newman, John |
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HAWLEY, MELISSA - University Of California |
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BARILE, DANIELA - University Of California |
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MILLS, DAVID - University Of California |
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RAYBOULD, H - University Of California |
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Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 3/1/2017 Publication Date: 3/9/2017 Citation: Hamilton, K.M., Ronveaux, C.C., Rust, B., Newman, J.W., Hawley, M., Barile, D., Mills, D., Raybould, H.E. 2017. Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice. American Journal of Physiology - Gastrointestinal and Liver Physiology. 312:G474–G487. https://doi.org/10.1152/ajpgi.00427.2016. DOI: https://doi.org/10.1152/ajpgi.00427.2016 Interpretive Summary: An alteration in the normal microbial community of the intestine can increase gut permeability, and may promote weight gain in models of high-fat (HF) diet-induced obesity (DIO). It is not known however if decreasing intestinal permeability is necessary or sufficient for weight loss. Sugar polymers in milk (i.e. milk oligosaccharides; MO) are considered prebiotics, having beneficial effects on the intestine, but have not been evaluated in DIO models. In this study we hypothesized that consumption of MO from cows (i.e. BMO) will prevent the deleterious effect of HF diet on intestinal permeability and prevent the obese phenotype. To test this, C57BL/6 mice were fed a control diet (LF), HF (40% fat/kcal), or HF + prebiotic (6%/Kg BMO or inulin) for 1, 3 or 6 weeks and gut microbiota content and function along with intestinal permeability, a were assessed in the ileum, cecum and colon. Addition of BMO to the HF diet attenuated weight gain, decreased adiposity and decreased caloric intake; inulin supplementation had no significant effect on weight gain or adiposity. BMO and inulin completely abolished the HF diet-induced increase in paracellular and transcellular permeability in the small and large intestine. BMO prevented HF-diet induced microbial dysbiosis; in contrast, inulin supplementation altered phylogenetic diversity and decreased species richness. Both BMO and inulin increased abundance of beneficial microbes Bifidobacterium and Lactobacillus in the ileum. Addition of BMO to the HF diet completely prevented increases in intestinal permeability and reduced, but did not prevent weight gain in DIO. Technical Abstract: Objective: Microbial dysbiosis and increased intestinal permeability is a target for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO); however, it is not known whether decreased intestinal permeability is necessary or sufficient for weight loss. Prebiotic milk oligosaccharides (MO) have been shown to benefit the host intestine, but have not been used in DIO. We hypothesized that preventing the deleterious effect of HF diet on intestinal permeability by supplementation of bovine MO will prevent the obese phenotype. Design: C57BL/6 mice were fed a control diet (LF), HF (40% fat/kcal), or HF + prebiotic (6%/Kg BMO or inulin) for 1, 3 or 6 weeks. Gut microbiota and intestinal permeability were assessed in the ileum, cecum and colon. Results: Addition of BMO to the HF diet attenuated weight gain, decreased adiposity and decreased caloric intake; inulin supplementation had no significant effect on weight gain or adiposity. BMO and inulin completely abolished the HF diet-induced increase in paracellular and transcellular permeability in the small and large intestine. BMO prevented HF-diet induced microbial dysbiosis; in contrast, inulin supplementation altered phylogenetic diversity and decreased species richness. Both BMO and inulin increased abundance of beneficial microbes Bifidobacterium and Lactobacillus in the ileum. Conclusions: Addition of BMO to the HF diet completely prevented increases in intestinal permeability and was partially effective to prevent weight gain in DIO |
