title: The prebiotics 3'Sialyllactose and 6'Sialyllactose diminish stressor-induced anxiety-like behavior and colonic microbiota alterations: Evidence for effects on the gut-brain axis.
abstract: There are extensive bidirectional interactions between the gut microbiota and the central nervous system (CNS), and studies demonstrate that stressor exposure significantly alters gut microbiota community structure. We tested whether oligosaccharides naturally found in high levels in human milk, which have been reported to impact brain development and enhance the growth of beneficial commensal microbes, would prevent stressor-induced alterations in gut microbial community composition and attenuate stressor-induced anxiety-like behavior. Mice were fed standard laboratory diet, or laboratory diet containing the human milk oligosaccharides 3'Sialyllactose (3'SL) or 6'Sialyllactose (6'SL) for 2 weeks prior to being exposed to either a social disruption stressor or a non-stressed control condition. Stressor exposure significantly changed the structure of the colonic mucosa-associated microbiota in control mice, as indicated by changes in beta diversity. The stressor resulted in anxiety-like behavior in both the light/dark preference and open field tests in control mice. This effect was associated with a reduction in immature neurons in the dentate gyrus as indicated by doublecortin (DCX) immunostaining. These effects were not evident in mice fed milk oligosaccharides; stressor exposure did not significantly change microbial community structure in mice fed 3'SL or 6'SL. In addition, 3'SL and 6'SL helped maintain normal behavior on tests of anxiety-like behavior and normal numbers of DCX+ immature neurons. These studies indicate that milk oligosaccharides support normal microbial communities and behavioral responses during stressor exposure, potentially through effects on the gut microbiota-brain axis.
authors.affiliation: Division of Biosciences, The College of Dentistry, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA. Electronic address: andrew.tarr@tufts.edu.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tarr
authors.affiliation: Division of Biosciences, The College of Dentistry, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Galley
authors.affiliation: Division of Biosciences, The College of Dentistry, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Sydney E
authors.initials: SE
authors.lastname: Fisher
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, 2400 W. Lloyd Expressway, Evansville, IN 47721, USA.
authors.forename: Maciej
authors.initials: M
authors.lastname: Chichlowski
authors.affiliation: Mead Johnson Pediatric Nutrition Institute, 2400 W. Lloyd Expressway, Evansville, IN 47721, USA; Division of Nutritional Sciences, University of Illinois Urbana-Champaign, 905 S. Goodwin Ave., Urbana, IL 61801, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Berg
authors.affiliation: Division of Biosciences, The College of Dentistry, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA; Department of Pediatrics, The Ohio State University Wexner Medical Center, Medical Center Dr., Columbus, OH 43210, USA; Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43206, USA. Electronic address: michael.bailey2@nationwidechildrens.org.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bailey
mesh_terms: D000818:Animals; D001007:Anxiety / Q000382:microbiology*; D015992:Body Mass Index; D001921:Brain / Q000382:microbiology*; D049109:Cell Proliferation; D003345:Corticosterone / Q000097:blood; D000089662:Doublecortin Protein; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D007785:Lactose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000382:microbiology; D009844:Oligosaccharides / Q000008:administration & dosage*; D013154:Spleen / Q000382:microbiology; D013315:Stress, Psychological / Q000382:microbiology*
chemical_list: C421467:3'-sialyllactose; C403777:6'-sialyllactose; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D015850:Interleukin-6; D009844:Oligosaccharides; D007785:Lactose; D003345:Corticosterone
keywords: Anxiety-like behavior; Doublecortin; Gut–brain axis; Hippocampus; Human milk oligosaccharides; Microbiota; Neurogenesis; Prebiotic; Sialyllactose