Raising the Alarm: Environmental Factors in the Onset and Maintenance of Chronic (Low-Grade) Inflammation in the Gastrointestinal Tract.

Chronic inflammatory disease of the gastrointestinal (GI) tract is defined by several pathophysiological characteristics, such as dysbiosis of the microbiota, epithelial barrier hyperpermeability, systemic dissemination of endotoxins and chronic inflammation. In addition to well-reported environmental factors in non-communicable disease, such as smoking, diet, and exercise, humans are frequently exposed to myriads more environmental factors, from pesticides to food additives. Such factors are ubiquitous across both our diet and indoor/outdoor environments. A major route of human exposure to these factors is ingestion, which frequently occurs due to their intentional addition (intentional food additives) and/or unintentional contamination (unintentional food contaminants) of food products-often linked to environmental pollution. Understanding how this persistent, diverse exposure impacts GI health is of paramount importance, as deterioration of the GI barrier is proposed to be the first step towards systemic inflammation and chronic disease. Therefore, we aim to evaluate the impact of ingestion of environmental factors on inflammatory processes in the GI tract. In this review, we highlight human exposure to intentional food additives (e.g. emulsifiers, bulking agents) and unintentional food contaminants (e.g. persistent organic pollutants, pesticides, microplastics), then present evidence for their association with chronic disease, modification of the GI microbiota, increased permeability of the GI barrier, systemic dissemination of endotoxins, local (and distal) pro-inflammatory signalling, and induction of oxidative stress and/or endoplasmic reticulum stress. We also propose a link to NLRP3-inflammasome activation. These findings highlight the contribution of common environmental factors towards deterioration of GI health and the induction of pathophysiology associated with onset and maintenance of chronic inflammation in the GI tract.