nutrients Review Role of Maternal Microbiota and Nutrition in Early-Life Neurodevelopmental Disorders Anissa Daliry * and Evelyn Nunes Goulart da Silva Pereira   Citation: Daliry, A.; Pereira, E.N.G.d.S. Role of Maternal Microbiota and Nutrition in Early-Life Neurodevelopmental Disorders. Nutrients 2021, 13, 3533. https://doi.org/10.3390/nu13103533 Academic Editors: Vicente Andreu-Fernández and Giorgia Sebastiani Received: 8 July 2021 Accepted: 24 August 2021 Published: 9 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil; evyspereira@gmail.com * Correspondence: daliry@ioc.fiocruz.br; Tel.: +55-212562-1312 Abstract: The rise in the prevalence of obesity and other related metabolic diseases has been paralleled by an increase in the frequency of neurodevelopmental problems, which has raised the likelihood of a link between these two phenomena. In this scenario, maternal microbiota is a possible linking mechanistic pathway. According to the “Developmental Origins of Health and Disease” paradigm, environmental exposures (in utero and early life) can permanently alter the body’s structure, physiol- ogy, and metabolism, increasing illness risk and/or speeding up disease progression in offspring, adults, and even generations. Nutritional exposure during early developmental stages may induce susceptibility to the later development of human diseases via interactions in the microbiome, includ- ing alterations in brain function and behavior of offspring, as explained by the gut–brain axis theory. This review provides an overview of the implications of maternal nutrition on neurodevelopmental disorders and the establishment and maturation of gut microbiota in the offspring. Keywords: gut microbiota; neurodevelopmental disorders; obesity; gut–brain axis; maternal diet 1. Introduction Over the last 50 years, the prevalence of adult and childhood obesity has increased worldwide, reaching pandemic proportions [1]. Overweight and obesity affect over 1.9 bil- lion adults, with 650 million of them being obese [2]. Obesity, which is the main risk factor for cardiovascular diseases, cancer, diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD), accounts for more than 70% of early deaths worldwide and is the leading cause of mortality and premature disability [3]. The increase in the prevalence of obesity and other related metabolic diseases has been paralleled by an increase in neurological problems, both in adults and in children [4–7]. Epi- demiologic studies have found a link between maternal metabolic diseases and offspring’s neurodevelopmental and psychiatric morbidity, including intellectual disability, cognitive impairment, autism spectrum disorders (ASD), and attention deficit hyperactivity disorder (ADHD). Obesity in mothers is linked to a 3.6-fold greater risk of intellectual disability or cognitive impairment in their children [8–11]. In addition, a positive association between high maternal body mass index (BMI) and ASD in offspring is widely observed (odds ratio range from 1.5 to 1.7) [12–15]. This risk is increased by preterm birth [14], high gestational weight gain [15], gestational or pre-gestational diabetes [12,13] and preeclamp- sia [16]. Large cohort studies have shown that ADHD symptoms in offspring increase in a dose-dependent manner accordingly to maternal pre-pregnancy BMI increase, from overweight to obese [17]. Other studies have reported a 1.6- to 2.8-fold greater risk of ADHD in offspring of obese mothers [18–20]. The exact etiology underlying neurodevelopmental disorders remains a challenge, but several genetic and nongenetic (exposome) factors are known to interact early in life to influence the risk for developing neurological diseases [21]. During pregnancy and early life, several environmental factors could influence the risk for developing neurode- velopmental disorders, including dietary pattern (healthy or unhealthy), socioeconomic Nutrients 2021, 13, 3533. https://doi.org/10.3390/nu13103533 https://www.mdpi.com/journal/nutrients