Pesticides and Their Impairing Effects on Epithelial Barrier Integrity, Dysbiosis, Disruption of the AhR Signaling Pathway and Development of Immune-Mediated Inflammatory Diseases

Abstract

The environmental and occupational risk we confront from agricultural chemicals increases as their presence in natural habitats rises to hazardous levels, building a major part of the exposome. This is of particular concern in low- and middle-income countries, such as Brazil, known as a leading producer of agricultural commodities and consumer of pesticides. As long as public policies continue to encourage the indiscriminate use of pesticides and governments continue to support this strategy instead of endorsing sustainable agricultural alternatives, the environmental burden that damages epithelial barriers will continue to grow. Chronic exposure to environmental contaminants in early life can affect crucial barrier tissue, such as skin epithelium, airways, and intestine, causing increased permeability, leaking, dysbiosis, and inflammation, with serious implications for metabolism and homeostasis. This vicious cycle of exposure to environmental factors and the consequent damage to the epithelial barrier has been associated with an increase in immune-mediated chronic inflammatory diseases. Understanding how the harmful effects of pesticides on the epithelial barrier impact cellular interactions mediated by endogenous sensors that coordinate a successful immune system represents a crucial challenge. In line with the epithelial barrier hypothesis, this narrative review reports the available evidence on the effects of pesticides on epithelial barrier integrity, dysbiosis, AhR signaling, and the consequent development of immune-mediated inflammatory diseases.

Pesticides: Unintended Impact on the Hidden World of Gut Microbiota

“…Intestinal epithelial cells act as an essential barrier in delimiting the invasion of host tissues by bacteria and other microbes and coordinating the functions of the subepithelial immune cells. Pesticides have been implicated in disrupting the epithelial barriers of the host, possibly by the disruption of tight junctions, such as claudins, and adherent junctions, like cadherins, in a ROS-dependent manner, thereby leading to increased permeability of the epithelial barrier [ 75 ]. For example, in an early study conducted by Tirelli et al, chlorpyrifos was shown to affect the epithelial barrier, as demonstrated using colon tissue-derived Caco2 cell lines, which showed a marked decrease in the expression of tight junction molecules [ 76 ].…”

Pesticide-Induced Inflammation at a Glance

“…Epithelial barriers are continuously exposed to various aggressors, and the gastrointestinal epithelial barrier's homeostasis relies on the balance of immune response, its components, and a healthy microbiota [25]. There is evidence that pesticides, such as CPF, can impact the intestinal barrier, as Huang et al (2019) described a significant increase in TNF-α messenger RNA (mRNA) expression in the colon, suggesting that CPF intensified colon inflammation [26].…”

The impact of outdoor pollution and extreme temperatures on asthma‐related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma

“…26,34,36 Organophosphorus (OP) insecticides can enhance AHR by disrupting the negative feedback control of cholinergic regulation in the lungs. 34,37,38 As a direct result of climate change extreme temperatures (heat waves and cold spells) are increasing in intensity, frequency, and duration causing significant stress in all living organisms. The biological impact of extreme temperatures (structural changes, enzyme function disruption, and damage through reactive oxygen or nitrogen species) can be mitigated through adaptive mechanisms such as the generation of heat shock proteins, antioxidants, and others; however, these mechanisms may likely become inadequate with further global warming.…”

“…In the form of aerosols or gases, pesticides damage the epithelial barrier and stimulate irritant receptors in the airways with neurogenic inflammation that adds to the chronic inflammation in asthma leading to exacerbation or loss of control 26,34,36 . Organophosphorus (OP) insecticides can enhance AHR by disrupting the negative feedback control of cholinergic regulation in the lungs 34,37,38 …”