Shang Xinchi, Che Xinghua, Ma Kai, Guo Wenxue, Wang Shanshan, Sun Zhi Peng, Xu Wei, Zhang Yongquan
Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin, 150070, China; College of Life Science, Northeast Agricultural University, Harbin, 150036, China.
Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin, 150070, China.
Environ Pollut. 2025 Mar 1;368:125759. doi: 10.1016/j.envpol.2025.125759. Epub 2025 Jan 27.
Cr(VI) is widely used in industry and has high toxicity, making it one of the most common environmental pollutants. Long-term exposure to Cr(VI) can cause metabolic disorders and tissue damage. However, the effects of Cr(VI) on liver and gut microbes in fish have rarely been reported. In this study, 240 fish were randomly divided into 3 groups: the control group, low-dose Cr(VI) group (0.5 mg/L), and high-dose Cr(VI) group (2 mg/L). The mechanism by which Cr(VI) affects the enterohepatic axis of common carp was elucidated via multiomic analysis, serology, histomorphology, and physiological and biochemical indices. The results revealed that Cr(VI) stress led to hepatocyte damage, nuclear lysis, inflammatory cell infiltration, and vacuolated degeneration. The structure of the intestinal villi was severely damaged, and the length and width of the intestinal villi were significantly reduced. We also found that the accumulation of Cr(VI) in tissues increased in a concentration-dependent manner, and the content of Cr(VI) in each tissue increased in the order of gut > gill > liver > muscle. Multiple omics studies have revealed that chronic Cr(VI) stress leads to disturbances in the intestinal flora, with a significant reduction in the abundance of the beneficial bacterium Akkermansia and a significant increase in the abundance of the harmful bacterium Escherichia/Shigella. Intestinal injury and dysbiosis lead to an increase in blood LPS levels, further inducing metabolic disorders in the liver. The metabolites in the liver, including geniposide, leucine, C17 sphingosine, and 9,10-DiHODE, were significantly increased, whereas the beneficial metabolites, such as carnitine propionate and palmitoyl ethanolamide, were significantly reduced. In conclusion, our results suggest that chronic Cr(VI) stress leads to disturbances in gut microbial homeostasis and disturbed fatty acid and amino acid metabolism in the liver. LPS released into the bloodstream reaches the liver through the portal circulation, further exacerbating Cr(VI) stress-induced hepatotoxicity. This study revealed the mechanism of Cr(VI) toxicity to the liver-microbiota-gut axis of common carp. Our study provides new insights into the effects of Cr(VI) on the liver-microbiota-gut axis.
六价铬（Cr(VI)）在工业中广泛使用且毒性很高，使其成为最常见的环境污染物之一。长期接触六价铬会导致代谢紊乱和组织损伤。然而，六价铬对鱼类肝脏和肠道微生物的影响鲜有报道。在本研究中，240条鱼被随机分为3组：对照组、低剂量六价铬组（0.5毫克/升）和高剂量六价铬组（2毫克/升）。通过多组学分析、血清学、组织形态学以及生理和生化指标，阐明了六价铬影响鲤鱼肠肝轴的机制。结果显示，六价铬胁迫导致肝细胞损伤、核溶解、炎性细胞浸润和空泡变性。肠绒毛结构严重受损，肠绒毛的长度和宽度显著减小。我们还发现，六价铬在组织中的积累呈浓度依赖性增加，各组织中六价铬的含量按肠道>鳃>肝脏>肌肉的顺序增加。多项组学研究表明，慢性六价铬胁迫导致肠道菌群紊乱，有益菌阿克曼氏菌的丰度显著降低，有害菌大肠杆菌/志贺氏菌的丰度显著增加。肠道损伤和生态失调导致血液中脂多糖（LPS）水平升高，进而诱导肝脏代谢紊乱。肝脏中的代谢产物，包括栀子苷、亮氨酸、C17鞘氨醇和9,10 - 二羟基十八碳二烯酸（9,10 - DiHODE）显著增加，而有益代谢产物，如丙酸肉碱和棕榈酰乙醇胺则显著减少。总之，我们的结果表明，慢性六价铬胁迫导致肠道微生物稳态紊乱以及肝脏中脂肪酸和氨基酸代谢紊乱。释放到血液中的脂多糖通过门静脉循环到达肝脏，进一步加剧六价铬胁迫诱导的肝毒性。本研究揭示了六价铬对鲤鱼肝脏 - 微生物群 - 肠道轴的毒性机制。我们的研究为六价铬对肝脏 - 微生物群 - 肠道轴的影响提供了新的见解。
