title: Prebiotic milk oligosaccharides prevent development of obese phenotype, impairment of gut permeability, and microbial dysbiosis in high fat-fed mice.
abstract: Microbial dysbiosis and increased intestinal permeability are targets for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO). Prebiotic milk oligosaccharides (MO) have been shown to benefit the host intestine but have not been used in DIO. We hypothesized that supplementation with bovine MO would prevent the deleterious effect of HF diet on the gut microbiota and intestinal permeability and attenuate development of the obese phenotype. C57BL/6 mice were fed a control diet, HF (40% fat/kcal), or HF + prebiotic [6%/kg bovine milk oligosaccharides (BMO) or inulin] for 1, 3, or 6 wk. Gut microbiota and intestinal permeability were assessed in the ileum, cecum, and colon. Addition of BMO to the HF diet significantly attenuated weight gain, decreased adiposity, and decreased caloric intake; inulin supplementation also lowered weight gain and adiposity, but this did not reach significance. BMO and inulin completely abolished the HF diet-induced increase in paracellular and transcellular permeability in the small and large intestine. Both BMO and inulin increased abundance of beneficial microbesBifidobacteriumandLactobacillusin the ileum. However, inulin supplementation altered phylogenetic diversity and decreased species richness. We conclude that addition of BMO to the HF diet completely prevented increases in intestinal permeability and microbial dysbiosis and was partially effective to prevent weight gain in DIO.NEW & NOTEWORTHYThis study provides the first report of the effects of prebiotic bovine milk oligosaccharides on the host phenotype of high-fat diet-induced obesity in mice.
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, California.
authors.forename: M Kristina
authors.identifier: http://orcid.org/0000-0003-0293-7043
authors.initials: MK
authors.lastname: Hamilton
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, California.
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Ronveaux
authors.affiliation: Department of Nutrition, University of California Davis, Davis, California.|National Institutes of Health West Coast Metabolomics Center, University of California Davis, Davis, California.
authors.forename: Bret M
authors.initials: BM
authors.lastname: Rust
authors.affiliation: Department of Nutrition, University of California Davis, Davis, California.|National Institutes of Health West Coast Metabolomics Center, University of California Davis, Davis, California.|Obesity and Metabolism Research Unit, United States Department of Agriculture Davis, Western Human Nutrition Research Center, Davis, California.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, California.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hawley
authors.affiliation: Department of Food Science and Technology, University of California Davis, Davis, California.|Foods for Health Institute, University of California Davis, Davis, California; and.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barile
authors.affiliation: Department of Food Science and Technology, University of California Davis, Davis, California.|Foods for Health Institute, University of California Davis, Davis, California; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Mills
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, California; heraybould@ucdavis.edu.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Raybould
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D064806:Dysbiosis / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology / Q000503:physiopathology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000737:chemistry*; D009765:Obesity / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009844:Oligosaccharides / Q000008:administration & dosage*; D056692:Prebiotics / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D009844:Oligosaccharides; D056692:Prebiotics
keywords: adiposity; epithelial permeability; obesity; prebiotic