ReviewPer- and polyfluoroalkyl substances exposure and its influence on the intestinal barrier: An overview on the advances
Graphical abstract
Introduction
Per- and polyfluoroalkyl substances (PFAS) refer to a class of synthesized compounds that contain at least one fully fluorinated methyl or methylene carbon atom. Commonly described as “forever chemicals” for their extreme resistance to biodegradation, PFAS have been widely used as water, grease, and stain repellents and surfactants in fire-fighting foam (Glüge et al., 2020). Now that PFAS have been detected in various environmental media, human exposure to PFAS can occur through multiple routes including dietary intake, drinking water, skin absorption and inhalation of household dust (Ragnarsdóttir et al., 2022; Sunderland et al., 2019). It has been reported that ingested PFAS are readily absorbed through the gastrointestinal tract of mammals and humans (Lupton et al., 2012). Consequently, they can be transmitted to the blood and other bodily tissues (e.g., gut, liver, and kidney) and induce subsequent adverse health effects (Costello et al., 2022; Xu et al., 2020b). In addition, given the long half-life of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) (nearly 5 years in humans), the health risks of exposure to PFAS will persist in the long term (Olsen et al., 2007).
The role of intestinal homeostasis in metabolic health and disease has been an active area of study. The intestine represents the largest interface between the human and the environment and performs a variety of homeostatic functions (Gustafsson et al., 2021; Mukherjee and Hooper, 2015). In addition to ensuring the absorption of nutrients, the intestine forms a practical internal barrier to protect the host from harmful substances and microorganisms in the intestinal lumen. The intestinal barrier contains epithelial cells, mucus layer, microbial components and immune cells located in the lamina propria and can be generally divided into four categories, namely physical, chemical, microbiological, and immune barriers (Cui et al., 2019; Hao et al., 2021). However, the integrity of these barriers can be modulated by several exogenous factors, e.g., antibiotics, low-fiber diets, and environmental pollutants, and could further trigger the development of autoimmune, metabolic and aging-related diseases (Albillos et al., 2020).
An increasing number of studies have paid attention to the impacts of PFAS on gut health in recent years. It has been found that PFAS can accumulate in the intestine and cause damage to the intestinal barrier, such as the disruption of tight junctions and increased permeability between epithelial cells, as well as microecosystem disruption (Lai et al., 2018; Shi et al., 2020; Wang et al., 2020a). In addition, PFAS exposure may also be associated with intestinal and extra-intestinal disorders. Nevertheless, although some reviews were found focusing on the degradation of PFAS by microbial (Lim, 2021; Wackett, 2021; Zhang et al., 2021), few studies have reviewed the toxic effects of PFAS on the intestinal barrier function as well as the intestinal microenvironment in animals and humans. Under these circumstances, it is necessary to review the knowledge about the adverse effects of PFAS exposure on the intestinal barrier system, and to dissect the causes and coping strategies of these adverse effects.
Herein, we aimed to summarize the available evidence regarding the sources and routes of human exposure to PFAS, and expound the absorption and transportation of PFAS within the gastrointestinal tract. Subsequently, relevant studies on the adverse effects of PFAS exposure on the intestinal barrier system were interpreted in detail. We also sorted out the associations between PFAS and intestinal diseases and extra-intestinal disorders, and discussed potential intervention strategies. Finally, the research prospects achieved and future perspectives are discussed. The purpose of this review is to give an overview of the current knowledge of health effects and directions for future investigation, and bring forward some hints to mitigate the intestinal toxicity problem of PFAS by manipulating the gut microbiota.
Section snippets
Sources of human exposure
As anthropogenic chemicals, environmental PFAS can come from direct and indirect sources. Fluorochemical manufacturing plants, metal plating, textile and paper coating, semiconductor production, and aqueous film-forming foam applications are considered direct sources of PFAS to the environment (Prevedouros et al., 2006). The production or waste disposal processes in such industries could be directly responsible for the release and contamination of PFAS, spreading it throughout the environment.
Absorption and transport of PFAS within the gastrointestinal tract
PFAS are highly efficiently absorbed in animals and humans (Lupton et al., 2012). The vast majority of PFAS entering the body are absorbed in the gastrointestinal tract, then passed into the bloodstream, and subsequently conveyed to various tissues. A large percentage of the total PFAS is retained in serum, liver, and kidney, and some can also accumulate in the intestine (Pérez et al., 2013). Ultimately, PFAS leave the body by urine or feces. Therefore, the impacts of PFAS on the intestinal
Destruction of the intestinal barriers by PFAS exposure
The intestine is an innate barrier that maintains the homeostasis of the intestinal environment and prevents the invasion of harmful substances and pathogens into the organism. The intestinal barrier is a multilayered structure consisting of interconnected physical, chemical, immune, and microbiological barriers (Fig. 1A). Because of the difficulty in obtaining human intestinal tissue, most of the current studies are focused on toxicological effects of PFAS on intestinal barriers in animals or
Discussion and future prospects
Considering the risks of human health and ecological environment, some long-chain PFAS like PFOA and PFOS have been phased out of production in many regions in the world over the last 10 to 15 years (UN Stockholm Convention, 2019). Therefore, various kinds of alternatives to conventional PFAS have been produced and used widely, such as short-chain homologs (PFBA, PFBS and PFHxA), functionalized perfluoropolyethers (PFPEs), for example, perfluoroether carboxylic (PFECAs), perfluoroether sulfonic
CRediT authorship contribution statement
Jiaoyang Li: Conceptualization, Methodology, Visualization, Writing – original draft. Lei Wang: Conceptualization, Methodology, Writing – review & editing. Xin Zhang: Writing – review & editing. Peng Liu: Visualization. Zhuoma Deji: Writing – review & editing. Yudong Xing: Writing – review & editing. Yan Zhou: Writing – review & editing. Xia Lin: Validation. Zhenzhen Huang: Conceptualization, Methodology, Validation, Writing – review & editing, Funding acquisition, Supervision, Project
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
The authors gratefully acknowledge financial support to the National Natural Science Foundation of China (NO. 81903368).
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The authors contribute equally to this work.