Esophageal viral and bacterial microbiome unbalances characterize achalasia

Abstract

Achalasia is a rare neuromuscular disorder of the esophagus whose pathogenesis is poorly understood. It is characterized by the loss of nerve cells in the esophagus, failure of the lower esophageal sphincter to relax, and impaired esophageal peristalsis. In this study, we re-analyzed transcriptomics data from blood and esophageal tissue samples of achalasia patients publicly available. Blood analysis showed hyperactivation of the immune system and dysfunction of the nervous system, consistent with the hypothesis of immune-mediated pathogenesis leading to neuronal loss. Mucosal tissue analysis e showed a remarkable unbalance in virome and bacteriome compositions in achalasia. In particular, bacterial diversity was reduced across the esophagus in achalasia compared to healthy controls, and in the distal esophagus bacteria associated with the healthy state, such as Firmicutes, Tenericutes, and Bacteroidetes, were less represented if not completely absent. Importantly, the only other component of the microbiota that varied significantly between achalasia and controls was the virome. Bacteriophages that parasite Firmicutes were strongly enriched in the esophagus supporting a predator-prey interaction. In conclusion, our study opens new horizons on a circulating signature of achalasia and the role of viral-bacterial interactions in orchestrating mucosal homeostasis and possibly disease pathogenesis. Key summaryAchalasia is a rare swallowing disorder with unknown causes. The role of gut microbiota, especially viruses, in achalasia is unclear. This study investigated the differences in viral and bacterial communities between achalasia patients and healthy people, and how they affect the esophageal mucosa. The findings may help develop new diagnostic tools and therapies based on novel hypotheses about the pathogenesis of achalasia.