长期暴露于无机砷[As(III) 和 As(V)]影响约2亿人，并与某些类型的癌症发生率增加有关。饮用水是暴露的主要途径，因此，在流行病区，肠道粘膜会不断接触到金属loid。然而，关于无机As对肠道毒性的研究很少。本研究的目的是评估长期暴露于As(III)对肠道粘膜及其相关微生物群落的毒性。为此，BALB/c小鼠通过饮水暴露于As(III)(15和30mg/L) 6个月。As(III)处理会增加反应性氧化物（43-64%）和脂质过氧化物（8-51% ）的水平。还观察到炎症反应的增加，表现为粪便乳铁蛋白（23-29%）和粘膜中的嗜中性粒细胞浸润的增加。As(III)还诱发了结肠前列腺炎性细胞因子水平的增加（24-201%）和某些前列腺炎症信号通路的激活。还观察到减少腺细胞数和粘液产生。此外，As(III)暴露导致了肠道微生物α多样性的变化，但β多样性没有差异。这表明一些分类群的丰度受到As(III)的显着影响，尽管人口的组成并未显示显着的变化。差异分类群的分析与此一致，21个ASV的丰度或变异受到影响，特别是家族Muribaculaceae的ASV。肠道微生物代谢也受到影响，因为观察到粪便中短链脂肪酸的浓度降低。对肠道屏障的不同组成部分的影响可能是As(III)处理小鼠中通透性增加的原因，这表现为粪便白蛋白的增加（48-66%）。此外，30mg/L的As(III)处理动物的血清脂多糖结合蛋白和TNF-α水平增加，表明存在低水平的系统性炎症。 版权所有©2023 Elsevier B.V.

Chronic exposure to inorganic arsenic [As(III) and As(V)] affects about 200 million people, and is linked to a greater incidence of certain types of cancer. Drinking water is the main route of exposure, so, in endemic areas, the intestinal mucosa is constantly exposed to the metalloid. However, studies on the intestinal toxicity of inorganic As are scarce. The objective of this study was to evaluate the toxicity of a chronic exposure to As(III) on the intestinal mucosa and its associated microbiota. For this purpose, BALB/c mice were exposed during 6 months through drinking water to As(III) (15 and 30 mg/L). Treatment with As(III) increased reactive oxygen species (43-64%) and lipid peroxidation (8-51%). A pro-inflammatory response was also observed, evidenced by an increase in fecal lactoferrin (23-29%) and mucosal neutrophil infiltration. As(III) also induced an increase in the colonic levels of pro-inflammatory cytokines (24-201%) and the activation of some pro-inflammatory signaling pathways. Reductions in the number of goblet cells and mucus production were also observed. Moreover, As(III) exposure resulted in changes in gut microbial alpha diversity but no differences in beta diversity. This suggested that the abundance of some taxa was significantly affected by As(III), although the composition of the population did not show significant alterations. Analysis of differential taxa agreed with this, 21 ASVs were affected in abundance or variability, especially ASVs from the family Muribaculaceae. Intestinal microbiota metabolism was also affected, as reductions in fecal concentration of short-chain fatty acids were observed. The effects observed on different components of the intestinal barrier may be responsible of the increased permeability in As(III) treated mice, evidenced by an increase in fecal albumin (48-66%). Moreover, serum levels of Lipopolysaccharide binding proteins and TNF-α were increased in animals treated with 30 mg/L of As(III), suggesting a low-level systemic inflammation.Copyright © 2023 Elsevier B.V. All rights reserved.