PMID- 26426902 OWN - NLM STAT- MEDLINE DCOM- 20160614 LR - 20220321 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 10 DP - 2015 TI - N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota. PG - e0139721 LID - 10.1371/journal.pone.0139721 [doi] LID - e0139721 AB - 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. METHODS AND 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. FAU - Pusceddu, Matteo M AU - Pusceddu MM AD - Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland. FAU - El Aidy, Sahar AU - El Aidy S AD - APC Microbiome Institute, University College Cork, Cork, Ireland; Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands. FAU - Crispie, Fiona AU - Crispie F AD - Teagasc, Moorepark, Cork, Ireland. FAU - O'Sullivan, Orla AU - O'Sullivan O AD - Teagasc, Moorepark, Cork, Ireland. FAU - Cotter, Paul AU - Cotter P AD - APC Microbiome Institute, University College Cork, Cork, Ireland; Teagasc, Moorepark, Cork, Ireland. FAU - Stanton, Catherine AU - Stanton C AD - Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland; Teagasc, Moorepark, Cork, Ireland. FAU - Kelly, Philip AU - Kelly P AD - Teagasc, Moorepark, Cork, Ireland. FAU - Cryan, John F AU - Cryan JF AD - APC Microbiome Institute, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland. FAU - Dinan, Timothy G AU - Dinan TG AD - Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; APC Microbiome Institute, University College Cork, Cork, Ireland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151001 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Fatty Acids, Omega-3) SB - IM EIN - PLoS One. 2015;10(10):e0142228. PMID: 26517367 MH - Animals MH - Behavior, Animal/*drug effects MH - Fatty Acids, Omega-3/*pharmacology MH - Female MH - Gastrointestinal Microbiome/*drug effects MH - Male MH - *Maternal Deprivation MH - Neuropsychological Tests MH - Rats MH - Rats, Sprague-Dawley MH - Stress, Psychological/*drug therapy/microbiology PMC - PMC4591340 COIS- Competing Interests: The authors have the following interests. The APC has conducted research funded by Pfizer, GlaxoSmithKline, Proctor and Gamble, Mead Johnson, Suntory and Cremo. TGD also has grant support from the Health Research Board Ireland (HRA_POR/2011/23 HRA_POR/2012/32, and HRA-POR-2014-647) and European FP7 and has been an invited speaker at meetings organised by Servier, Lundbeck, Janssen, Astra-Zeneca. JFC has received grant support from the Health Research Board of Ireland (Grant number HRA_POR/2012/32), Science Foundation Ireland (Investigator Award Grant No. 12/IA/1537), European Community's Seventh Framework Programme (Grant number FP7/2007-2013 under Grant Agreement no. 278948 (TACTICS-Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndrome)). JFC has been an invited speaker at meetings organised by Mead Johnson and Yakult. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors. EDAT- 2015/10/02 06:00 MHDA- 2016/06/15 06:00 PMCR- 2015/10/01 CRDT- 2015/10/02 06:00 PHST- 2015/07/10 00:00 [received] PHST- 2015/09/16 00:00 [accepted] PHST- 2015/10/02 06:00 [entrez] PHST- 2015/10/02 06:00 [pubmed] PHST- 2016/06/15 06:00 [medline] PHST- 2015/10/01 00:00 [pmc-release] AID - PONE-D-15-30329 [pii] AID - 10.1371/journal.pone.0139721 [doi] PST - epublish SO - PLoS One. 2015 Oct 1;10(10):e0139721. doi: 10.1371/journal.pone.0139721. eCollection 2015.