Inflammatory Signatures of Maternal Obesity as Risk Factors for Neurodevelopmental Disorders: Role of Maternal Microbiota and Nutritional Intervention Strategies

Abstract

Obesity is a main risk factor for the onset and the precipitation of many non-communicable diseases. This condition, which is associated with low-grade chronic systemic inflammation, is of main concern during pregnancy leading to very serious consequences for the new generations. In addition to the prominent role played by the adipose tissue, dysbiosis of the maternal gut may also sustain the obesity-related inflammatory milieu contributing to create an overall suboptimal intrauterine environment. Such a condition here generically defined as "inflamed womb" may hold long-term detrimental effects on fetal brain development, increasing the vulnerability to mental disorders. In this review, we will examine the hypothesis that maternal obesity-related gut dysbiosis and the associated inflammation might specifically target fetal brain microglia, the resident brain immune macrophages, altering neurodevelopmental trajectories in a sex-dependent fashion. We will also review some of the most promising nutritional strategies capable to prevent or counteract the effects of maternal obesity through the modulation of inflammation and oxidative stress or by targeting the maternal microbiota.

Keywords: gut microbiota; high-fat diet; inflammation; maternal obesity; microglia; nutritional intervention strategies; oxidative stress.

Figure 1

Obesogenic diets before and during pregnancy may trigger a dramatic loss of the homeostatic balance between the beneficial and potentially pathogenic bacteria in maternal gut leading to a condition of dysbiosis. This enhances gut inflammation that weakens the intestinal barrier (leaky gut) eventually resulting in the transplacental passage of bacteria and microbial compounds in the womb providing an immunogenic challenge to the fetus. SCFAs the main end-product of bacterial metabolism hold anti-inflammatory properties; they are tightly regulated during pregnancy to provide optimal fetal development. Obesity-related dysbiosis and inflammation may alter levels of SCFAs reaching the fetus. Finally, although still debated, the colonization of the fetal gut by maternally-derived bacteria (fetal gut seeding) in a condition of maternal dysbiosis might negatively affect the development of the gut-brain axis. The above-mentioned mechanisms may all contribute to provide a suboptimal intrauterine environment characterized by elevated systemic inflammation (inflamed womb) in turn affecting homeostasis in the developing fetal brain (inflamed brain) with microglia being a preferential target. Developing nutraceutical strategies, based on safe and feasible compounds (NAC, MFGM, LC-PUFA), aimed at counteracting gestational weight gain, reducing inflammation and oxidative stress is of paramount importance to support optimal brain development and to promote mental health throughout life. This image is original and has been created with BioRender.