The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia
© 2024. Japanese Society of Gastroenterology..
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 (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 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 LC20, 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Journal of gastroenterology - 59(2024), 5 vom: 12. Apr., Seite 361-375 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ikeda, Hiroko [VerfasserIn] |
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| Links: |
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| Themen: |
Culture Media, Conditioned |
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| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 22.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00535-024-02088-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369620933 |
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| 100 | 1 | |a Ikeda, Hiroko |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The interplay between alterations in esophageal microbiota associated with Th17 immune response and impaired LC20 phosphorylation in achalasia |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 22.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. Japanese Society of Gastroenterology. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a RESULTS: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 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 | ||
| 520 | |a CONCLUSIONS: In LES of patients with achalasia, hypophosphorylation of LC20, 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Myosin light chain phosphorylation | |
| 650 | 4 | |a Protein kinase C-potentiated phosphatase-inhibitor protein of 17 kDa | |
| 650 | 4 | |a Th-17 | |
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| 650 | 7 | |a Culture Media, Conditioned |2 NLM | |
| 700 | 1 | |a Ihara, Eikichi |e verfasserin |4 aut | |
| 700 | 1 | |a Takeya, Kosuke |e verfasserin |4 aut | |
| 700 | 1 | |a Mukai, Koji |e verfasserin |4 aut | |
| 700 | 1 | |a Onimaru, Manabu |e verfasserin |4 aut | |
| 700 | 1 | |a Ouchida, Kenoki |e verfasserin |4 aut | |
| 700 | 1 | |a Hata, Yoshitaka |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Xiaopeng |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Yoshimasa |e verfasserin |4 aut | |
| 700 | 1 | |a Sasaki, Taisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Saito, Fumiyo |e verfasserin |4 aut | |
| 700 | 1 | |a Eto, Masumi |e verfasserin |4 aut | |
| 700 | 1 | |a Nakayama, Jiro |e verfasserin |4 aut | |
| 700 | 1 | |a Oda, Yoshinao |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Masafumi |e verfasserin |4 aut | |
| 700 | 1 | |a Inoue, Haruhiro |e verfasserin |4 aut | |
| 700 | 1 | |a Ogawa, Yoshihiro |e verfasserin |4 aut | |
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