Effects of Early Life Exposure to Di(2-Ethylhexyl) Phthalate on Jejunal Morphology, Sucrase Activity, and Colonic Microbiota Composition in Young Pigs

The diesters of 1,2-benzenedicarboxylic acid (phthalic acid), or phthalates, are multifunctional chemicals used in personal care products, medications, and plastics. Phthalate metabolites are also found in human milk and infant formula. However, their impact on intestinal development and microbiota composition in early life is understudied. Herein, the effect of di-(2-ethylhexyl) phthalate (DEHP) on growth, intestinal morphology, enzyme activity, and microbiota composition was assessed. Piglets (two-day-old, n = 24) were randomized to receive either 20 mg (DEHP20) or 200 mg (DEHP200)/kg body weight (BW)/day in corn oil. A control group (CON, 0 mg phthalate) received the same volume of corn oil as DEHP200. After 21 days, tissue and urine samples were collected. DEHP did not affect weight gain. Urinary DEHP metabolite concentrations increased in a dose-dependent fashion. Jejunal villus length was significantly shorter in the DEHP200 than CON and DEHP20, while villus area was smaller in DEHP200 than DEHP20 but not CON. Crypt depth and area were higher in DEHP200 than DEHP20, but neither differed from CON. Additionally, jejunal sucrase activity was higher in the DEHP200 than CON. Bacterial alpha diversity differed significantly between DEHP groups and CON in the ascending colon, while beta diversity revealed significant differences between DEHP200 and CON and DEHP20. The abundance of Christensenellaceae R-7 group, Romboutsia , Lachnospiraceae UCG-004, Odoribacter , and Sphaerochaeta , among others, differed in DEHP-exposed vs. CON animals. Thus, daily exposure to phthalates during infancy changes the villus structure and disaccharidase activity in the small intestine and these changes may be modulated by the colonic bacterial community.