Postnatal prebiotic supplementation in rats affects adult anxious behaviour, hippocampus, electrophysiology, metabolomics, and gut microbiota
Sonia O. Spitzer,
Andrzej Tkacz,
Helene M. Savignac,
Matthew Cooper,
Natasa Giallourou,
Edward O. Mann,
David M. Bannerman,
Jonathan R. Swann,
Daniel C. Anthony,
Philip S. Poole,
Philip W.J. Burnet
Affiliations
Sonia O. Spitzer
Department of Psychiatry, University of Oxford, Warneford Lane, Oxford, OX3 7JX, UK
Andrzej Tkacz
Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK
Helene M. Savignac
Quadram Institute, Rosalind Franklin Road, Norwich Research Park, Norwich NR4 7UQ, UK
Matthew Cooper
Department of Physiology, Anatomy and Genomics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK; Oxford Ion Channel Initiative, University of Oxford, Oxford OX1 3PT, UK
Natasa Giallourou
Department of Metabolism, Digestion and Reproduction, Imperial College, South Kensington Campus, London SW7 2AZ, UK
Edward O. Mann
Department of Physiology, Anatomy and Genomics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK; Oxford Ion Channel Initiative, University of Oxford, Oxford OX1 3PT, UK
David M. Bannerman
Oxford Ion Channel Initiative, University of Oxford, Oxford OX1 3PT, UK; Department of Experimental Psychology, University of Oxford, Anna Watts Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford OX2 6GG, UK
Jonathan R. Swann
Department of Metabolism, Digestion and Reproduction, Imperial College, South Kensington Campus, London SW7 2AZ, UK; School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
Daniel C. Anthony
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
Philip S. Poole
Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK
Philip W.J. Burnet
Department of Psychiatry, University of Oxford, Warneford Lane, Oxford, OX3 7JX, UK; Corresponding author
Summary: We have shown previously that prebiotic (Bimuno galacto-oligosacharides, B-GOS®) administration to neonatal rats increased hippocampal NMDAR proteins. The present study has investigated the effects of postnatal B-GOS® supplementation on hippocampus-dependent behavior in young, adolescent, and adult rats and applied electrophysiological, metabolomic and metagenomic analyses to explore potential underlying mechanisms. The administration of B-GOS® to suckling, but not post-weaned, rats reduced anxious behavior until adulthood. Neonatal prebiotic intake also reduced the fast decay component of hippocampal NMDAR currents, altered age-specific trajectories of the brain, intestinal, and liver metabolomes, and reduced abundance of fecal Enterococcus and Dorea bacteria. Our data are the first to show that prebiotic administration to rats during a specific postnatal period has long-term effects on behavior and hippocampal physiology. The study also suggests that early-life prebiotic intake may affect host brain function through the reduction of stress-related gut bacteria rather than increasing the proliferation of beneficial microbes.
