Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime

Q. Leyrolle, F. Decoeur, G. Briere, C. Amadieu, A. R. A. A. Quadros, I. Voytyuk, C. Lacabanne, A. Benmamar-Badel, J. Bourel, A. Aubert, A. Sere, F. Chain, L. Schwendimann, B. Matrot, T. Bourgeois, S. Grégoire, J. G. Leblanc, A. De Moreno De Leblanc, P. Langella, G. R. Fernandes, L. Bretillon, C. Joffre, R. Uricaru, P. Thebault, P. Gressens, J. M. Chatel, S. Layé, A. Nadjar
Neuropsychopharmacol.. 2020-08-11; :
DOI: 10.1038/s41386-020-00793-7

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Leyrolle Q(1)(2), Decoeur F(1), Briere G(1)(3), Amadieu C(1), Quadros ARAA(1), Voytyuk I(1), Lacabanne C(1), Benmamar-Badel A(1), Bourel J(1), Aubert A(1), Sere A(1), Chain F(4), Schwendimann L(2), Matrot B(2), Bourgeois T(2), Grégoire S(5), Leblanc JG(6), De Moreno De Leblanc A(6), Langella P(4), Fernandes GR(7), Bretillon L(5), Joffre C(1), Uricaru R(3), Thebault P(3), Gressens P(2)(8), Chatel JM(4), Layé S(9), Nadjar A(10).

Author information:
(1)University Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France.
(2)Université de Paris, NeuroDiderot, Inserm, F-75019, Paris, France.
(3)CNRS, Bordeaux INP, LaBRI, UMR 5800, F-33400, Talence, France.
(4)Micalis Institute, INRAE, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
(5)Centre des Sciences du Goût et de l’Alimentation, AgroSup Dijon, CNRS, INRAE, Université Bourgogne Franche-Comté, Dijon, France.
(6)CERELA-CONICET, San Miguel de Tucuman, 4000, Tucuman, Argentina.
(7)Rene Rachou Institute – Oswaldo Cruz Foundation, Belo Horizonte, MG, Brazil.
(8)Centre for the Developing Brain, Department of Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, SE1 7EH, UK.
(9)University Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France. .
(10)University Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000, Bordeaux, France. .

Maternal immune activation (MIA) and poor maternal nutritional habits are risk factors for the occurrence of neurodevelopmental disorders (NDD). Human studies show the deleterious impact of prenatal inflammation and low n-3 polyunsaturated fatty acid (PUFA) intake on neurodevelopment with long-lasting consequences on behavior. However, the mechanisms linking maternal nutritional status to MIA are
still unclear, despite their relevance to the etiology of NDD. We demonstrate here that low maternal n-3 PUFA intake worsens MIA-induced early gut dysfunction, including modification of gut microbiota composition and higher local inflammatory reactivity. These deficits correlate with alterations of microglia-neuron crosstalk pathways and have long-lasting effects, both at transcriptional and behavioral levels. This work highlights the perinatal period as a critical time window, especially regarding the role of the gut-brain axis in neurodevelopment, elucidating the link between MIA, poor nutritional habits, and NDD.

Auteurs Bordeaux Neurocampus