Molecular and Environmental Toxicology, University of Wisconsin-Madison, Madison, WI, US; Biotechnology Center, University of Wisconsin-Madison, Madison, WI, US.
Department of Oncology, University of Wisconsin-Madison, Madison, WI, US.
Environ Int. 2024 Aug;190:108805. doi: 10.1016/j.envint.2024.108805. Epub 2024 Jun 10.
The human gut microbiome, the host, and the environment are inextricably linked across the life course with significant health impacts. Consisting of trillions of bacteria, fungi, viruses, and other micro-organisms, microbiota living within our gut are particularly dynamic and responsible for digestion and metabolism of diverse classes of ingested chemical pollutants. Exposure to chemical pollutants not only in early life but throughout growth and into adulthood can alter human hosts' ability to absorb and metabolize xenobiotics, nutrients, and other components critical to health and longevity. Inflammation is a common mechanism underlying multiple environmentally related chronic conditions, including cardiovascular disease, multiple cancer types, and mental health. While growing research supports complex interactions between pollutants and the gut microbiome, significant gaps exist. Few reviews provide descriptions of the complex mechanisms by which chemical pollutants interact with the host microbiome through either direct or indirect pathways to alter disease risk, with a particular focus on inflammatory pathways. This review focuses on examples of several classes of pollutants commonly ingested by humans, including (i) heavy metals, (ii) persistent organic pollutants (POPs), and (iii) nitrates. Digestive enzymes and gut microbes are the first line of absorption and metabolism of these chemicals, and gut microbes have been shown to alter compounds from a less to more toxic state influencing subsequent distribution and excretion. In addition, chemical pollutants may interact with or alter the selection of more harmful and less commensal microbiota, leading to gut dysbiosis, and changes in receptor-mediated signaling pathways that alter the integrity and function of the gut intestinal tract. Arsenic, cadmium, and lead (heavy metals), influence the microbiome directly by altering different classes of bacteria, and subsequently driving inflammation through metabolite production and different signaling pathways (LPS/TLR4 or proteoglycan/TLR2 pathways). POPs can alter gut microbial composition either directly or indirectly depending on their ability to activate key signaling pathways within the intestine (e.g., PCB-126 and AHR). Nitrates and nitrites' effect on the gut and host may depend on their ability to be transformed to secondary and tertiary metabolites by gut bacteria. Future research should continue to support foundational research both in vitro, in vivo, and longitudinal population-based research to better identify opportunities for prevention, gain additional mechanistic insights into the complex interactions between environmental pollutants and the microbiome and support additional translational science.
人体肠道微生物群、宿主和环境在整个生命周期中是紧密相连的，对健康有重大影响。肠道内的微生物群由数万亿细菌、真菌、病毒和其他微生物组成，它们特别具有动态性，负责消化和代谢各种摄入的化学污染物。化学污染物的暴露不仅在生命早期，而且在整个生长过程中，甚至在成年后，都可能改变人体宿主吸收和代谢外来物质、营养物质和其他对健康和长寿至关重要的成分的能力。炎症是多种与环境有关的慢性疾病的共同机制，包括心血管疾病、多种癌症类型和心理健康问题。尽管越来越多的研究支持污染物和肠道微生物群之间的复杂相互作用，但仍存在重大差距。很少有综述描述化学污染物通过直接或间接途径与宿主微生物群相互作用，改变疾病风险的复杂机制，特别是炎症途径。本综述重点介绍了人类通常摄入的几类污染物的例子，包括 (i) 重金属、(ii) 持久性有机污染物 (POPs) 和 (iii) 硝酸盐。消化酶和肠道微生物是这些化学物质吸收和代谢的第一道防线，并且已经表明肠道微生物可以将化合物从较少毒性状态改变为更毒性状态，从而影响随后的分布和排泄。此外，化学污染物可能与或改变选择更有害和较少共生的微生物群，导致肠道菌群失调，并改变受体介导的信号通路，从而改变肠道的完整性和功能。砷、镉和铅（重金属）通过改变不同类别的细菌直接影响微生物组，随后通过代谢产物的产生和不同的信号通路（LPS/TLR4 或蛋白聚糖/TLR2 通路）驱动炎症。POPs 可以通过改变肠道内的关键信号通路，直接或间接地改变肠道微生物的组成（例如，PCB-126 和 AHR）。硝酸盐和亚硝酸盐对肠道和宿主的影响可能取决于它们被肠道细菌转化为次级和三级代谢物的能力。未来的研究应继续支持体外、体内和纵向人群研究的基础研究，以更好地确定预防机会，深入了解环境污染物和微生物组之间的复杂相互作用的机制，并支持更多的转化科学。
