Eosinophilic Esophagitis and Microbiota: State of the Art

Abstract

Eosinophilic esophagitis (EoE) is a chronic, food-triggered, immune-mediated disease of the oesophagus, clinically characterized by symptoms referred to oesophagal dysfunction, and histologically defined by an eosinophil productive inflammation of the oesophagal mucosa, among other cell types. The involvement of an adaptive Th2-type response to food antigens in EoE was known since 2000; several cytokines and chemokines promote food-specific responses, during which local production of IgE, but also IgG4 derived from plasma cells in lamina propria of oesophagal mucosa might play an important role. Evidence pointing towards a possible role for the innate immunity in EoE has arisen recently. Together, this evidence gives rise to a potential role that the innate immune system in general, and also the microbial pattern recognition receptors (PRRs) might play in EoE pathogenesis. Among PRRs, Toll-like receptors (TLRs) are type-I transmembrane receptors expressed both on epithelial and lamina propria cells with the capacity to distinguish between pathogen and commensal microbes. As TLRs in the different intestinal epithelia represent the primary mechanism of epithelial recognition of bacteria, this evidence underlines that oesophagal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease. The oesophagal mucosa hosts a resident microbiota, although in a smaller population as compared with other districts of the gastrointestinal tract. Few studies have focused on the composition of the microbiota of the normal oesophagus alone. Still, additional information has come from studies investigating the oesophagal microbiota in disease and including healthy patients as controls. Our review aims to describe all the evidence on the oesophagal and intestinal microbiota in patients with EoE to identify the specific features of dysbiosis in this condition.

Type 2 Inflammation in Eosinophilic Esophagitis: From Pathophysiology to Therapeutic Targets

“…The finding that premature delivery, cesarean birth, early antibiotic exposure, lack of breastfeeding and lack of early microbial exposure are risk factors for the development of EoE ( Radano et al, 2014 ; Jensen and Dellon, 2018 ) has revived the idea of the Hygiene Hypothesis also in EoE ( Mennini et al, 2021 ).…”

Role of Short Chain Fatty Acids and Apolipoproteins in the Regulation of Eosinophilia-Associated Diseases

“…Similar to other eosinophilia-associated diseases, microbiome research in the field of eosinophilic esophagitis has increased in recent years. On the one hand, several reports indicated that patients with EoE have a certain esophageal microbiome distinct from that of non-EoE controls [ 249 , 250 , 251 , 252 , 253 , 254 , 255 ]; however, thus far the causal relationship that regulates these changes is still uncertain (reviewed in [ 256 ]). On the other hand, no significant differences in the esophageal microbiome were observed between newly diagnosed EoE cases and non-EoE controls in adults, while use of proton pump inhibitors was significantly associated with five taxa including Absconditabacteria at the phylum level and Burkholderia at the genus level [ 257 ].…”

The Gut Microbiome and Its Implication in the Mucosal Digestive Disorders

“…The EoE activity seems not to directly affect the bacteria load of the esophageal mucosa but it is associated with changes in microbiota diversity. It involves a shift from a majority of Gram-positive bacteria to an increase in Gram negative bacteria, similar to microbiota changes of composition seen in reflux related disease [ 31 , 46 ]. Pseudomonadota such as Neisseria , Corynebacterium and Haemophilus spp.…”