title: Neonatal environment exerts a sustained influence on the development of the intestinal microbiota and metabolic phenotype.
abstract: The postnatal environment, including factors such as weaning and acquisition of the gut microbiota, has been causally linked to the development of later immunological diseases such as allergy and autoimmunity, and has also been associated with a predisposition to metabolic disorders. We show that the very early-life environment influences the development of both the gut microbiota and host metabolic phenotype in a porcine model of human infants. Farm piglets were nursed by their mothers for 1 day, before removal to highly controlled, individual isolators where they received formula milk until weaning at 21 days. The experiment was repeated, to create two batches, which differed only in minor environmental fluctuations during the first day. At day 1 after birth, metabolic profiling of serum by (1)H nuclear magnetic resonance spectroscopy demonstrated significant, systemic, inter-batch variation which persisted until weaning. However, the urinary metabolic profiles demonstrated that significant inter-batch effects on 3-hydroxyisovalerate, trimethylamine-N-oxide and mannitol persisted beyond weaning to at least 35 days. Batch effects were linked to significant differences in the composition of colonic microbiota at 35 days, determined by 16 S pyrosequencing. Different weaning diets modulated both the microbiota and metabolic phenotype independently of the persistent batch effects. We demonstrate that the environment during the first day of life influences development of the microbiota and metabolic phenotype and thus should be taken into account when interrogating experimental outcomes. In addition, we suggest that intervention at this early time could provide 'metabolic rescue' for at-risk infants who have undergone aberrant patterns of initial intestinal colonisation.
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Merrifield
authors.affiliation: Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.|Infection and Immunity, School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, North Somerset, UK.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Lewis
authors.affiliation: Nestlé Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Berger
authors.affiliation: Korrigan Sciences Ltd., Maidenhead, UK.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Silke S
authors.initials: SS
authors.lastname: Heinzmann
authors.affiliation: Nestlé Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Charton
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: Lutz
authors.initials: L
authors.lastname: Krause
authors.affiliation: Institute of Social & Cultural Anthropology, Oxford University, Oxford, UK.
authors.forename: Nadine S
authors.initials: NS
authors.lastname: Levin
authors.affiliation: Nestlé Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland.
authors.forename: Swantje
authors.initials: S
authors.lastname: Duncker
authors.affiliation: Nestlé Research Centre, Vers-chez-les-Blanc, Lausanne, Switzerland.
authors.forename: Annick
authors.initials: A
authors.lastname: Mercenier
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Infection and Immunity, School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, North Somerset, UK.
authors.forename: Mick
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Biomolecular Medicine, Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D003106:Colon / Q000254:growth & development / Q000378:metabolism / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development / Q000382:microbiology*; D010641:Phenotype; D013552:Swine / Q000254:growth & development / Q000382:microbiology* / Q000502:physiology; D014886:Weaning