AI Article Synopsis
- Achalasia is an esophageal disorder with unclear causes, and the study investigates how changes in smooth muscle contractions and inflammation contribute to its development, along with the role of esophageal microbiota.
- Analysis of esophageal samples from patients showed that those with achalasia had significantly lower levels of myosin light chain phosphorylation compared to healthy controls, along with increased levels of certain inflammatory cytokines.
- The findings suggest that both the hypophosphorylation of myosin light chains and changes in the esophageal microbiota may play a role in the impaired contractility and worsening of achalasia symptoms.
Article Abstract
Background: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development.
Methods: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia.
Results: Approximately 30% of 20-kDa myosin light chains (LC) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media.
Conclusions: In LES of patients with achalasia, hypophosphorylation of LC, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia.
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| http://dx.doi.org/10.1007/s00535-024-02088-w | DOI Listing |
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