Arsenic Ingested Early in Life Is More Readily Absorbed: Mechanistic Insights from Gut Microbiota, Gut Metabolites, and Intestinal Morphology and Functions

作者：Hongyu Wang, Shan Chen, Rong-Yue Xue, Xin-Ying Lin, Jin-Lei Yang, Yao-Sheng Zhang, Shiwei Li, Albert L. Juhasz, Q. Lena, Dongmei Zhou, Hongbo Li · 发表于：Environmental Science & Technology · 年份：2022 · DOI：10.1021/acs.est.2c04584 · 被引用次数：19 · 研究领域：Arsenic contamination and mitigation、Heavy Metal Exposure and Toxicity、Fluoride Effects and Removal

Early-life arsenic (As) exposure is a particular health concern. However, it is unknown if As ingested early in life is more readily absorbed from the gastrointestinal (GI) tract, i.e., higher in oral bioavailability. Here, weanling (3-week) and adult (6-week-old) female mice were exposed to arsenate in the diet (10 μg g –1 ) over a 3-week period with As oral bioavailability estimated using As urinary excretion as the bioavailability endpoint. The As urinary excretion factor was 1.54-fold higher in weanling mice compared to adult mice (82.2 ± 7.29 versus 53.1 ± 3.73%), while weanling mice also showed 2.28-, 1.50-, 1.48-, and 1.89-fold higher As concentration in small intestine tissue, blood, liver, and kidneys, demonstrating significantly higher As oral bioavailability of early-life exposure. Compared to adult mice, weanling mice significantly differed in gut microbiota, but the difference did not lead to remarkable differences in As biotransformation in the GI tract or tissue and in overall gut metabolite composition. Although the expression of several metabolites (e.g., atrolactic acid, hydroxyphenyllactic acid, and xanthine) was up-regulated in weanling mice, they had limited ability to elevate As solubility in the intestinal tract. Compared to adult mice, the intestinal barrier function and intestinal expression of phosphate transporters responsible for arsenate absorption were similar in weanling mice. However, the small intestine of weanling mice was characterized by mo...