title: Maternal Weaning Modulates Emotional Behavior and Regulates the Gut-Brain Axis.
abstract: Evidence shows that nutritional and environmental stress stimuli during postnatal period influence brain development and interactions between gut and brain. In this study we show that in rats, prevention of weaning from maternal milk results in depressive-like behavior, which is accompanied by changes in the gut bacteria and host metabolism. Depressive-like behavior was studied using the forced-swim test on postnatal day (PND) 25 in rats either weaned on PND 21, or left with their mother until PND 25 (non-weaned). Non-weaned rats showed an increased immobility time consistent with a depressive phenotype. Fluorescence in situ hybridization showed non-weaned rats to harbor significantly lowered Clostridium histolyticum bacterial groups but exhibit marked stress-induced increases. Metabonomic analysis of urine from these animals revealed significant differences in the metabolic profiles, with biochemical phenotypes indicative of depression in the non-weaned animals. In addition, non-weaned rats showed resistance to stress-induced modulation of oxytocin receptors in amygdala nuclei, which is indicative of passive stress-coping mechanism. We conclude that delaying weaning results in alterations to the gut microbiota and global metabolic profiles which may contribute to a depressive phenotype and raise the issue that mood disorders at early developmental ages may reflect interplay between mammalian host and resident bacteria.
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.|School of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG6 6AP, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Farshim
authors.affiliation: School of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, RG6 6AP, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Walton
authors.affiliation: School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading RG6 6AL, Reading, UK.
authors.forename: Bhismadev
authors.initials: B
authors.lastname: Chakrabarti
authors.affiliation: Food Production and Quality Division, School of Agriculture, Policy and Development, University of Reading, Earley Gate, Reading RG6 6AR, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Givens
authors.affiliation: School of Psychology and Clinical Language Sciences, Centre for Integrative Neuroscience and Neurodynamics, University of Reading RG6 6AL, Reading, UK.
authors.forename: Doug
authors.initials: D
authors.lastname: Saddy
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kitchen
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, South Kensington campus, Imperial College London SW7 2AZ, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: R Swann
authors.affiliation: School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.|Institute of Medical and Biomedical Education, St George's University of London, London SW17 0RE, UK.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bailey
mesh_terms: D000339:Affect; D000679:Amygdala / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D047009:Hathewaya histolytica / Q000502:physiology; D003863:Depression / Q000382:microbiology* / Q000503:physiopathology / Q000652:urine; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D041981:Gastrointestinal Tract / Q000254:growth & development / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D015870:Gene Expression; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D055442:Metabolome; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000378:metabolism*; D015398:Signal Transduction; D013315:Stress, Psychological / Q000382:microbiology* / Q000503:physiopathology / Q000652:urine; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014886:Weaning
chemical_list: D018045:Receptors, Oxytocin