title: N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota.
abstract: BACKGROUND
  Early life stress is a risk factor for many psychiatric disorders ranging from depression to anxiety. Stress, especially during early life, can induce dysbiosis in the gut microbiota, the key modulators of the bidirectional signalling pathways in the gut-brain axis that underline several neurodevelopmental and psychiatric disorders. Despite their critical role in the development and function of the central nervous system, the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the regulation of gut-microbiota in early-life stress has not been explored.
  
  
  RESULTS
  Here, we show that long-term supplementation of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (80% EPA, 20% DHA) n-3 PUFAs mixture could restore the disturbed gut-microbiota composition of maternally separated (MS) female rats. Sprague-Dawley female rats were subjected to an early-life stress, maternal separation procedure from postnatal days 2 to 12. Non-separated (NS) and MS rats were administered saline, EPA/DHA 0.4 g/kg/day or EPA/DHA 1 g/kg/day, respectively. Analysis of the gut microbiota in adult rats revealed that EPA/DHA changes composition in the MS, and to a lesser extent the NS rats, and was associated with attenuation of the corticosterone response to acute stress.
  
  
  CONCLUSIONS
  In conclusion, EPA/DHA intervention alters the gut microbiota composition of both neurodevelopmentally normal and early-life stressed animals. This study offers insights into the interaction between n-3 PUFAs and gut microbes, which may play an important role in advancing our understanding of disorders of mood and cognitive functioning, such as anxiety and depression.
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: Matteo M
authors.initials: MM
authors.lastname: Pusceddu
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
authors.forename: Sahar
authors.initials: S
authors.lastname: El Aidy
authors.affiliation: Teagasc, Moorepark, Cork, Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Crispie
authors.affiliation: Teagasc, Moorepark, Cork, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: O'Sullivan
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; Teagasc, Moorepark, Cork, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Cotter
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland; Teagasc, Moorepark, Cork, Ireland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Stanton
authors.affiliation: Teagasc, Moorepark, Cork, Ireland.
authors.forename: Philip
authors.initials: P
authors.lastname: Kelly
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D008297:Male; D008426:Maternal Deprivation; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D015525:Fatty Acids, Omega-3