Per- and polyfluoroalkyl substances exposure and its influence on the intestinal barrier: An overview on the advances

Highlights

• PFAS entering the gastrointestinal tract can disrupt the intestinal barrier system.

• Some PFAS alternatives showed certain intestinal toxicity in animal experiments.

• Effects of PFAS on the intestinal barrier need more human studies to consolidate.

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a class of artificially synthetic organic compounds that are hardly degraded in the natural environment. PFAS have been widely used for many decades, and the persistence and potential toxicity of PFAS are an emerging concern in the world. PFAS exposed via diet can be readily absorbed by the intestine and enter the circulatory system or accumulate directly at intestinal sites, which could interact with the intestine and cause the destruction of intestinal barrier. This review summarizes current relationships between PFAS exposure and intestinal barrier damage with a focus on more recent toxicological studies. Exposure to PFAS could cause inflammation in the gut, destruction of the gut epithelium and tight junction structure, reduction of the mucus layer, and induction of the toxicity of immune cells. PFAS accumulation could also induce microbial disorders and metabolic products changes. In addition, there are limited studies currently, and most available studies converge on the health risk of PFAS exposure for human intestinal disease. Therefore, more efforts are deserved to further understand potential associations between PFAS exposure and intestinal dysfunction and enable better assessment of exposomic toxicology and health risks for humans in the future.

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.