Gut epithelial barrier damage caused by dishwasher detergents and rinse aids

Ismail Ogulur; Yagiz Pat; Tamer Aydin; Duygu Yazici; Beate Rückert; Yaqi Peng; Juno Kim; Urszula Radzikowska; Patrick Westermann; Milena Sokolowska; Raja Dhir; Mubeccel Akdis; Kari Nadeau; Cezmi A Akdis

doi:10.1016/j.jaci.2022.10.020

Gut epithelial barrier damage caused by dishwasher detergents and rinse aids

J Allergy Clin Immunol. 2023 Feb;151(2):469-484. doi: 10.1016/j.jaci.2022.10.020. Epub 2022 Dec 1.

Authors

Affiliations

¹ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. Electronic address: ismail.ogulur@siaf.uzh.ch.
² Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Department of Medical Microbiology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin.
³ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
⁴ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
⁵ Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland; Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
⁶ SEED, Inc, Co, Los Angeles, Calif.
⁷ Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif.

PMID: 36464527
DOI: 10.1016/j.jaci.2022.10.020

Abstract

Background: The increased prevalence of many chronic inflammatory diseases linked to gut epithelial barrier leakiness has prompted us to investigate the role of extensive use of dishwasher detergents, among other factors.

Objective: We sought to investigate the effects of professional and household dishwashers, and rinse agents, on cytotoxicity, barrier function, transcriptome, and protein expression in gastrointestinal epithelial cells.

Methods: Enterocytic liquid-liquid interfaces were established on permeable supports, and direct cellular cytotoxicity, transepithelial electrical resistance, paracellular flux, immunofluorescence staining, RNA-sequencing transcriptome, and targeted proteomics were performed.

Results: The observed detergent toxicity was attributed to exposure to rinse aid in a dose-dependent manner up to 1:20,000 v/v dilution. A disrupted epithelial barrier, particularly by rinse aid, was observed in liquid-liquid interface cultures, organoids, and gut-on-a-chip, demonstrating decreased transepithelial electrical resistance, increased paracellular flux, and irregular and heterogeneous tight junction immunostaining. When individual components of the rinse aid were investigated separately, alcohol ethoxylates elicited a strong toxic and barrier-damaging effect. RNA-sequencing transcriptome and proteomics data revealed upregulation in cell death, signaling and communication, development, metabolism, proliferation, and immune and inflammatory responses of epithelial cells. Interestingly, detergent residue from professional dishwashers demonstrated the remnant of a significant amount of cytotoxic and epithelial barrier-damaging rinse aid remaining on washed and ready-to-use dishware.

Conclusions: The expression of genes involved in cell survival, epithelial barrier, cytokine signaling, and metabolism was altered by rinse aid in concentrations used in professional dishwashers. The alcohol ethoxylates present in the rinse aid were identified as the culprit component causing the epithelial inflammation and barrier damage.

Keywords: Alcohol ethoxylates; Caco-2; cytotoxicity; dishwasher detergents; epithelial barrier; inflammation; rinse aid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Detergents* / metabolism
Epithelial Cells* / metabolism
Gastrointestinal Tract
Humans
Intestinal Mucosa / metabolism
RNA / metabolism
Tight Junctions / metabolism
Up-Regulation

Substances

Detergents
RNA