Maternal dietary omega-3 deficiency worsens the deleterious effects of prenatal inflammation on the gut-brain axis in the offspring across lifetime.
Q LeyrolleF DecoeurG BriereC AmadieuAna Rita Agra de Almeida QuadrosI VoytyukC LacabanneA Benmamar-BadelJ BourelA AubertA SereF ChainL SchwendimannBoris MatrotT BourgeoisS GrégoireJean Guy LeBlancA De Moreno De LeblancP LangellaG R FernandesL BretillonC JoffreR UricaruP ThebaultP GressensJ M ChatelS LayéAgnès NadjarPublished in: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2020)
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.
Keyphrases
- birth weight
- fatty acid
- pregnancy outcomes
- oxidative stress
- pregnant women
- weight gain
- endothelial cells
- gene expression
- white matter
- traumatic brain injury
- type diabetes
- resting state
- adipose tissue
- physical activity
- high glucose
- multiple sclerosis
- high fat diet
- insulin resistance
- body mass index
- induced pluripotent stem cells
- preterm birth
- smoking cessation