Increased Gut Permeability and Bacterial Translocation after Chronic Chlorpyrifos Exposure in Rats

Abstract

The epithelium's barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs), multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier) during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC)-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR) and localization (using immunofluorescence) of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs). In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning) but not at day 60 (adulthood). At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal epithelium may be a risk factor for digestive inflammatory diseases.

Use of molecular typing to investigate bacterial translocation from the intestinal tract of chlorpyrifos-exposed rats

“…In conclusion, our earlier morphological and molecular analyses showed that long-lasting exposure to CPF (an organophosphate insecticide observed as food residues) altered the maturation of the rat intestine and was associated with intestinal dysbiosis and BT towards sterile organs [4, 5]. In the present study, we confirmed the occurrence of BT and validated the use of molecular typing in rats exposed to CPF in utero and during lactation.…”

“…Several previous studies have investigated the effect of CPF on the intestinal wall (ileum and colon) [4, 5]. Exposure to CPF decreases the mRNA expression of genes encoding the tight junction proteins (including claudin-4 and zonula-1); this increases intestinal permeability, enables BT and activates the immune system.…”

“…Tirelli et al [3] have shown that CPF increases membrane permeability in an enterocyte cell culture model. Furthermore, Joly Condette et al [4] showed for the first time that low-dose chlorpyrifos exposure in vivo causes morphological changes in the intestinal epithelium, alters intestinal permeability and increases bacterial translocation (BT, as detected by culture-based methods). In rats, this phenomenon is associated with (and probably caused by) failure of the intestine’s barrier function and an imbalance of in the intestinal microbiota [5].…”

Changes in Composition and Function of Human Intestinal Microbiota Exposed to Chlorpyrifos in Oil as Assessed by the SHIME® Model

“…In 2012, another study indicated that CPF is biotransformed by cytochrome P450 in the upper part of the small intestine [9]. Lastly, Joly Condette et al’s rat study showed for the first time that exposure to a low dose of pesticide causes morphological changes in the intestinal epithelium, increases intestinal permeability and bacterial translocation, and is associated with an imbalance in the intestinal microbiota [10,11]. …”

Human Oral Buccal Microbiomes Are Associated with Farmworker Status and Azinphos-Methyl Agricultural Pesticide Exposure

“…Hispanics have a disproportionate disease burden for many common diseases related to vasculature (i.e., diabetes and cardiovascular disease) (82)(83)(84)(85)(86)(87)(88)(89)(90) that have also been shown to have microbiome-related disease variables in many other experimental contexts (91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104). Dental health, bacterial infection, and peripheral vascular disease have many independent associations (105), and some of the etiology could be affected by systemic loosening of tight junctions as induced by organophosphates (78). In many other contexts, environmental pollutants have been shown to affect the microbiome (106), and here we show in humans the association between the composition of the microbiome and agricultural pesticide exposure.…”