Enduring Behavioral Effects Induced by Birth by Caesarean Section in the Mouse
- Creators
- Morais, Livia H.
- Golubeva, Anna V.
- Moloney, Gerard M.
- Moya-Pérez, Angela
- Ventura-Silva, Ana Paula
- Arboleya, Silvia
- Bastiaanssen, Thomaz F. S.
- O'Sullivan, Orla
- Rea, Kieran
- Borre, Yuliya
- Scott, Karen A.
- Patterson, Elaine
- Cherry, Paul
- Stilling, Roman
- Hoban, Alan E.
- El Aidy, Sahar
- Sequeira, Ana M.
- Beers, Sasja
- Moloney, Rachel D.
- Renes, Ingrid B.
- Wang, Shugui
- Knol, Jan
- Ross, R. Paul
- O'Toole, Paul W.
- Cotter, Paul D.
- Stanton, Catherine
- Dinan, Timothy G.
- Cryan, John F.
Abstract
Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown. Here, we demonstrated that birth by C-section results in marked but transient changes in microbiome composition in the mouse, in particular, the abundance of Bifidobacterium spp. was depleted in early life. Mice born by C-section had enduring social, cognitive, and anxiety deficits in early life and adulthood. Interestingly, we found that these specific behavioral alterations induced by the mode of birth were also partially corrected by co-housing with vaginally born mice. Finally, we showed that supplementation from birth with a Bifidobacterium breve strain, or with a dietary prebiotic mixture that stimulates the growth of bifidobacteria, reverses selective behavioral alterations in C-section mice. Taken together, our data link the gut microbiota to behavioral alterations in C-section-born mice and suggest the possibility of developing adjunctive microbiota-targeted therapies that may help to avert long-term negative consequences on behavior associated with C-section birth mode.
Additional Information
© 2020 The Authors. Published by Elsevier Under a Creative Commons license - Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) Received 10 October 2019, Revised 15 March 2020, Accepted 14 July 2020, Available online 20 August 2020. This publication has emanated from research supported in part by a Centre grant from Science Foundation Ireland (SFI) to the APC Microbiome Institute under grant number SFI/12/RC/2273. It was funded by the European Community's Seventh Framework Programme grant MyNewGut under grant agreement no. FP7/2007-2013 and Department of Agriculture, Food & the Marine, Ireland-funded TODDLERFOOD: Food Solutions for Replenishing Disrupted Microbiota in Toddlers (2014–2018) and SMARTFOOD: Science Based "Intelligent"/Functional and Medical Foods for Optimum Brain Health, Targeting Depression and Cognition (2013–2017). L.H.M. was funded by Science Without Borders, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), under the grant agreement number no. 11601-13-2 during manuscript preparation. The authors would like to thank Drs. Ken O'Riordan and Kiran Sandhu for assistance with figures; Dr. Gil Sharon for assisting on the data analyses; and Patrick Fitzgerald, Dr. Emmanuela Morelli, Dr. Gillard Lach, Dr. Ana Paula Ramos-Costa, Sofia Cussotto, Aoife Collery, Anne Marie Cusack, Colette Manley, and staff of the Biological Services Unit, University College Cork for technical support. Author Contributions. L.H.M. designed and performed the research, discussed and analyzed the data, and wrote the paper. G.M.M., A.V.G., A.M.P., and Y.B. designed and performed the research and analyzed the data. O.O.S., A.P.V.-S., K.S., E.P., R.S., A.E.H., T.F.S.B., P.C., S.E.A., S.B., S.A., and A.M.S. performed the research. K.R. assisted on the data analyses. R.P.R., J.K., S.W., I.B.R., P.W.O., P.D.C., and C.S. designed and discussed the data and assisted in writing the manuscript. J.F.C. and T.G.D. conceived the study, supervised, discussed and analyzed the data, and wrote the paper. Declaration of Interests. J.F.C., T.G.D., and C.S. have received research funding from Dupont Nutrition Biosciences APS, Cremo SA, Alkermes Inc., 4D Pharma PLC, Mead Johnson Nutrition, and Nutricia and have spoken at meetings sponsored by food and pharmaceutical companies. R.P.R. is a founder shareholder of Artugen Therapeutics. P.W.O. is a founder shareholder of 4D pharma Cork, Ltd. I.B.R., S.W., and J.K. are employees of Nutricia Research, Utrecht, the Netherlands. All other authors reported no biomedical financial interests or potential conflicts of interest.Attached Files
Published - 1-s2.0-S0960982220310691-main.pdf
Supplemental Material - 1-s2.0-S0960982220310691-mmc1.pdf
Supplemental Material - 1-s2.0-S0960982220310691-mmc2.xlsx
Supplemental Material - 1-s2.0-S0960982220310691-mmc3.xlsx
Supplemental Material - 1-s2.0-S0960982220310691-mmc4.xlsx
Supplemental Material - 1-s2.0-S0960982220310691-mmc5.xlsx
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Additional details
- Eprint ID
- 106471
- Resolver ID
- CaltechAUTHORS:20201105-160426379
- SFI/12/RC/2273
- Science Foundation, Ireland
- FP7/2007-2013/MyNewGut
- European Research Council (ERC)
- Department of Agriculture, Food and the Marine (Ireland)
- Science Without Borders
- 11601-13-2
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
- Created
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2020-11-06Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field