Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria?

Abstract

Genomic sequencing, bioinformatics, and initial speciation ( e.g. , relative abundance) of the commensal microbiome have revolutionized the way we think about the “human” body in health and disease. The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases, including those impacting the esophagus. Although relatively stable, there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome (EM) and the host. These changes are thought to be a product of age, diet, antibiotic and other medication use, oral hygiene, smoking, and/or expression of antibiotic products (bacteriocins) by other flora. These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation, systemic inflammation, and ultimately disease progression. Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is, therefore, not merely the result of esophageal mucosal exposure to corrosives ( i.e. , acid). Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade. Here, we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief ( i.e. , acid suppression).

Detecting potential causal relationship between gut microbiota and gastroesophageal reflux disease: a Mendelian randomization study

“…In contrast, microbial dysbiosis has been implicated in the pathogenesis of various diseases, including in ammation and cancers 34 . The role of GM in the development of different diseases has been extensively investigated and has garnered signi cant attention in relation to GERD pathogenesis 35 . The human GM, a complex assemblage of microorganisms residing in the digestive tract, comprises over 1500 species distributed across more than 50 phyla, with approximately 30-40 species accounting for 99% of bacterial presence 36 .…”

Epidemiology of Eosinophilic Esophagitis in Patients with Cystic Fibrosis: A Population-Based 5-Year Study

“…This raises the intriguing question of whether this unique group of patients with both conditions, CF with EoE, have a higher degree of atopy when compared to those with EoE or CF alone. The exact reason for this association between EoE, CF and atopic diseases is unclear but altered esophageal microbiome, dysregulated interactions between microbiota and gut mucosal immunity, could be a potential link between these conditions [ 12 13 14 15 16 17 ]. Similarly, prolonged antibiotic exposure in CF patients could predispose to atopic disorders via Th2 skewing [ 18 19 ].…”

Progress on the Mechanism of Visceral Hypersensitivity in Nonerosive Reflux Disease

“…This increase in sulfate-reducing Proteobacteria spp. and Bacteroidetes spp., along with hydrogen-producing Dorea spp., may be involved in the presence of NERD VH [ 51 ]. Gram-negative bacterial products activate TLRs that, on the esophageal endothelial cells, cause an inflammatory cascade and a microbial-brain-gut axis, which may also be the mechanisms of NERD VH [ 52 ].…”