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

• Published in: Scientific reports Vol. 7; no. 1; pp. 14472 - 12
• Main Authors: Malaisé, Yann, Menard, Sandrine, Cartier, Christel, Gaultier, Eric, Lasserre, Frédéric, Lencina, Corinne, Harkat, Cherryl, Geoffre, Nancy, Lakhal, Laïla, Castan, Isabelle, Olier, Maïwenn, Houdeau, Eric, Guzylack-Piriou, Laurence
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-11-2017; Nature Publishing Group
• Subjects: 13/106; 13/21; 13/31; 38/77; 631/250/347; 631/326; 631/443/319/1642; 64/60; 82/80; Adipose tissue; Animals; Animals, Newborn; Benzhydryl Compounds - adverse effects; Bisphenol A; Body weight; Body weight gain; Consumer products; Diabetes mellitus; Digestive system; Dysbacteriosis; Dysbiosis - etiology; Dysbiosis - physiopathology; Environmental Pollutants - adverse effects; Epidemiology; Feces - chemistry; Feces - microbiology; Female; Gastrointestinal Microbiome; Gastrointestinal tract; Glucose - metabolism; Helper cells; Homeostasis; Humanities and Social Sciences; Immune response; Immune system; Immune System - drug effects; Immune System - growth & development; Immune System - microbiology; Immune System - physiopathology; Immunoglobulin A; Immunoglobulin A - metabolism; Inflammation; Inflammation - etiology; Inflammation - microbiology; Inflammation - physiopathology; Insulin; Intestinal microflora; Intestine; Lamina propria; Life Sciences; Longitudinal Studies; Lymphocytes T; Macrophages; Male; Metabolic disorders; Mice, Inbred C3H; multidisciplinary; Obesity; Obesity - etiology; Obesity - microbiology; Obesity - physiopathology; Perinatal exposure; Phenols - adverse effects; Pregnancy; Prenatal Exposure Delayed Effects; Science; Science (multidisciplinary); Spleen; Time Factors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-15196-w

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.