Gut dysbiosis and impairment of immune system homeostasis in perinatally-exposed mice to Bisphenol A precede obese phenotype development

Abstract

Epidemiology evidenced the Bisphenol A (BPA), a chemical found in daily consumer products, as an environmental contributor to obesity and type II diabetes (T2D) in Humans. However, the BPA-mediated effects supporting these metabolic disorders are still unknown. Knowing that obesity and T2D are associated with low-grade inflammation and gut dysbiosis, we performed a longitudinal study in mice to determine the sequential adverse effects of BPA on immune system and intestinal microbiota that could contribute to the development of metabolic disorders. We observed that perinatal exposure to BPA (50 µg/kg body weight/day) induced intestinal and systemic immune imbalances at PND45, through a decrease of Th1/Th17 cell frequencies in the lamina propria concomitant to an increase of splenic Th1/Th17 immune responses. These early effects are associated with an altered glucose sensitivity, a defect of IgA secretion into faeces and a fall of faecal bifidobacteria relative to control mice. Such BPA-mediated events precede infiltration of pro-inflammatory M1 macrophages in gonadal white adipose tissue appearing with ageing, together with a decreased insulin sensitivity and an increased weight gain. Our findings provide a better understanding of the sequential events provoked by perinatal exposure to BPA that could support metabolic disorder development in later life.

The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model

“…Exposure to an endocrine-disrupting chemical such as BPA promotes adipogenesis and weight gain. This made BPA as a potential determinant of obesity 56 . This study also confirms the obesogenic impacts on male mice after BPA exposure.…”

Perinatal oral exposure to low doses of bisphenol A, S or F impairs gut barrier and immune functions in female offspring mice

“…This theory is called "the developmental origins of health and disease" [32]. We previously showed that gestational and lactational exposure to environmental relevant doses of BPA causes adverse effects on immune function in offspring mice [24,25], but no study has investigated the effect of BPS and BPF and its consequences on the immune system of offspring mice. During the neonatal period, the immune system, the intestinal epithelium and the microbiota form one entity, in which all parameters influence each other for their respective development until the equilibrium/homeostasis is reached.…”

“…1). Perinatal experiment was conducted as previously described [25]. Briefly, nulliparous female C3H/HeN mice (Janvier, Roubaix, France) were mated with male for 5 days and then individually isolated.…”

“…Indeed, we showed in previous studies that perinatal exposure to BPA increased the risk of food intolerance at adulthood, as well as the susceptibility to intestinal infection and/or to exacerbated mucosal inflammation [24]. More recently, we reported that perinatal exposure to BPA induced intestinal and systemic immune imbalances in male offspring mice at adulthood, through a decrease of Th1/Th17 cell frequencies in the small intestine lamina propria (siLP) concomitant to an increase of splenic Th1/Th17 immune responses [25]. In comparison, the same BPA perinatal exposure led in female offspring mice to a defect in dendritic cell maturation in the siLP and spleen associated with a decrease of activated and regulatory T cells in the siLP.…”

Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases

“…It has been proposed that EDCs may increase the susceptibility to these disorders by altering the adipose tissue, pancreas, liver, gastrointestinal tract, muscle, and brain homeostatic and hedonic pathways [4]. However, few studies have reported that the effects of EDCs on the gut microbiota can increase the risk of metabolic disorders such as obesity and diabetes [5,6].…”