Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero

Abstract

The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.

Prebiotic Supplementation During Gestation Induces a Tolerogenic Environment and a Protective Microbiota in Offspring Mitigating Food Allergy

“…Remarkably, at 6 weeks of age, we still observe tolerance biomarkers in pups antenatally exposed to prebiotics, including an increase of Treg and Breg associated with an increased IL-10 secretion, and an increased Th1 and Th2 response. We have already demonstrated that in utero the consumption of prebiotics promotes a pro-tolerogenic environment (25), and herein we demonstrate that this immune environment endures at least until 6 weeks of life. The increase in Breg numbers might be explained by the increased abundance of Lactobacillus in the fecal microbiota, as this family has been shown to promote the differentiation of Breg in the spleen and in the mesenteric lymph nodes (49).…”

“…Microbial transfers between mother and child might trigger immune responses in the fetus and the newborn that might shape the infant's IS development, the notion of "early life imprinting" of the IS (48). In this context, we already published that prebiotic supplementation during gestation increased the frequency of tolerogenic immune cells (Treg and Breg) in feto-maternal tissues and increased the level of SCFAs in the amniotic fluid (25). Interestingly, the frequency of Breg was also increased in the intestine and femurs of fetuses.…”

“…Pups born from mothers that received either a control diet or GOS/inulin diet, but were not sensitized to wheat, were used as controls (CTL and PB). For the mouse model of FA, 3-week-old female mice were intraperitoneally sensitized with two injections of 10 µg of wheat allergen 25 dissolved in phosphate-buffered saline (PBS; Gibco, Thermo Fisher Scientific, France) v/v of aluminum hydroxide (Anhydrogel 2%, InvivoGen, USA) separated by 10 days. One week after the last injection, mice were orally challenged with 20 mg of wheat allergen by intragastric probe.…”

“…We have recently published that prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that lasts over time ( 25 ). Indeed, this study highlighted the impact of GOS/inulin supplementation during gestation on 1) the modulation of the mother’s gut microbiota, leading to increased SCFA production; 2) the transfer of metabolites such as acetate and amino acids from mother to fetus in the amniotic fluid; 3) the tolerogenic environment induced in utero in feto-maternal tissues; and 4) the establishment of tolerogenic and Breg-mediated immune imprinting in the fetus that remains associated with Treg later in life.…”

Pathogenesis of Children’s Allergic Diseases: Refocusing the Role of the Gut Microbiota

“…Neonates demonstrate a complex microbiota in the gut within the week immediately following birth, with dynamic fluctuations in the composition of the gut microbiota until a stable adult microbiota composition is reached at the age of 2–2.5 years. Research suggests that facultative and aerotolerant bacteria such as lactic acid bacteria, Enterobacteria , and streptococci dominate the initial flora in the neonatal gut, followed by an increasing number of strict anaerobes, including Bifidobacterium, Clostridium, Bacteroides ( Bottacini et al, 2017 ; Milani et al, 2017 ; Brosseau et al, 2021 ).…”