Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Collaborative Innovation Center of Endoscopy, Shanghai, China.
Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Microbiol Res. 2023 Nov;276:127470. doi: 10.1016/j.micres.2023.127470. Epub 2023 Aug 7.
The gut microbiota plays a critical role in the appropriate development and maintenance of the enteric nervous system (ENS). Esophageal achalasia (EA) is a rare motility disorder characterized by the selective degeneration of inhibitory neurons in the esophageal myenteric plexus. This study aimed to evaluate the composition of the esophageal microbiota in achalasia and explore the potential microbial mechanisms involved in its pathogenesis.
The lower esophageal mucosal microbiota was analyzed in patients with achalasia and control participants using 16 S rRNA sequencing. The association between the esophageal microbiota and achalasia was validated by inducing esophageal dysbiosis in C57BL/10 J and C57BL/10ScNJ (TLR4KO) mice via chronic exposure to ampicillin sodium in their drinking water.
The esophageal microbiota in EA patients had lower diversity and a predominance of Gram-negative bacteria (Type II microbiota) compared to that in the healthy controls. Additionally, the relative abundance of Rhodobacter decreased significantly in patients with achalasia, which correlated with an enrichment of lipopolysaccharide (LPS) biosynthesis based on the COG database. Antibiotic-treated mice showed an esophageal microbiota characterized by increased abundance of Gram-negative bacteria (Type II microbiome), decreased abundance of Rhodobacter, and enriched LPS biosynthesis. Compared to the control and TLR4KO mice, the antibiotic-treated wild-type mice had higher LES resting pressure, increased LES contraction rate after carbachol stimulation, and decreased relaxation response to L-arginine. Moreover, the number of myenteric neurons decreased, while the number of lamina propria macrophages (LpMs) increased after antibiotic exposure. Furthermore, the TLR4-MYD88-NF-κB pathway was up-regulated, and the production of TNF-α, IL-1β, and IL-6 increased in the antibiotic-treated mice.
Patients with achalasia exhibit esophageal dysbiosis, which may induce aberrant esophageal motility.
肠道微生物群在肠神经系统（ENS）的适当发育和维持中起着关键作用。食管失弛缓症（EA）是一种罕见的运动障碍，其特征是食管肌间神经丛中的抑制性神经元选择性退化。本研究旨在评估食管失弛缓症患者食管微生物组的组成，并探讨其发病机制中涉及的潜在微生物机制。
使用 16S rRNA 测序分析食管失弛缓症患者和对照参与者的下食管黏膜微生物群。通过在饮用水中持续暴露于氨苄西林钠，在 C57BL/10J 和 C57BL/10ScNJ（TLR4KO）小鼠中诱导食管菌群失调，验证食管微生物群与食管失弛缓症的相关性。
与健康对照组相比，EA 患者的食管微生物群多样性较低，革兰氏阴性菌（II 型微生物群）占优势。此外，食管失弛缓症患者中罗得伯氏菌的相对丰度显著降低，这与基于 COG 数据库的内毒素生物合成富集相关。抗生素处理的小鼠表现出以下特征的食管微生物群：革兰氏阴性菌（II 型微生物组）丰度增加，罗得伯氏菌丰度降低，内毒素生物合成丰富。与对照组和 TLR4KO 小鼠相比，抗生素处理的野生型小鼠的 LES 静息压力更高，卡巴胆碱刺激后 LES 收缩率增加，对 L-精氨酸的松弛反应减少。此外，抗生素暴露后，肌间神经元数量减少，固有层巨噬细胞（LpM）数量增加。此外，TLR4-MYD88-NF-κB 通路上调，抗生素处理的小鼠 TNF-α、IL-1β 和 IL-6 的产生增加。
食管失弛缓症患者表现出食管菌群失调，这可能导致异常的食管运动。
