Effects of disruption of gut-liver-brain autonomic reflexes on various organs due to the progression of liver disease pathology

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02906
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Keio University
• Principal Investigator: Teratani Toshiaki 慶應義塾大学, 医学部(信濃町), 特任准教授 (40624408)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝肺相関 / 迷走神経

Outline of Final Research Achievements

Since the liver is an organ responsible for metabolism and detoxification, impaired liver function and liver disease are deeply involved in organ function and pathogenesis, including the digestive organs, spleen, heart, lungs, and kidneys. In particular, the respiratory disorder that occurs with liver disease is called hepatopulmonary syndrome, which threatens the patient's life itself in addition to decreasing the patient's quality of life. Although vasodilators accumulated due to chronic hepatic insufficiency have been considered the cause of hepatopulmonary syndrome, a detailed pathogenetic mechanism has not been demonstrated to date. Therefore, we analyzed the effects of the liver-brain axis on lung homeostasis in a mouse model. Resection of the hepatic branch of the vagus nerve increased group 2 innate lymphoid cells in the lung. These results suggest that liver lesions affect lung function and other functions through the afferent vagus nerve.

Free Research Field

消化器学

Academic Significance and Societal Importance of the Research Achievements

肝臓内を走行する神経ネットワークの維持に肝星細胞が重要な役割を果たしていることが明確となった。
そのため、肝臓病の発症および進展に伴う肝星細胞の形質変化が、肝臓-脳軸を脆弱にすることで、肺や代謝臓器に対して様々な影響を齎すと想定された。さらに、栄養応答性の求心性迷走神経が代謝疾患制御における重要なターゲットであることが本研究により示唆された。これらのデータは、肝臓病を背景とした肺疾患や代謝疾患に対して有効な治療法提案に繋がると考えられた。