Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, China.
Department of Gastroenterology, the Second Hospital of Shandong University, Jinan, China.
FASEB J. 2024 Oct 31;38(20):e70134. doi: 10.1096/fj.202401565RR.
Acute pancreatitis (AP) is a serious health problem that dysregulates intestinal microbiota. Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier in AP, but its effect on intestinal microbiota remains clear. To investigate the impact of Ang-(1-7) on AP-induced intestinal microbiota disorder and metabolites. We collected blood and fecal samples from 31 AP patients within 48 h after admission to the hospital, including 11 with mild AP (MAP), 14 with moderately severe AP (MSAP), six with severe AP (SAP). Mice were divided into four groups: control, AP, AP + Ang-(1-7) via tail vein injection, and AP + Ang-(1-7) via oral administration. The samples of mice were collected 12 h after AP. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. Fecal microbiota and metabolites analysis was performed via 16S rDNA sequencing and nontargeted metabolomics analysis, respectively. In patients, the abundance of beneficial bacteria (Negativicutes) decreased and pathogenic bacteria (Clostridium bolteae and Ruminococcus gnavus) increased in SAP compared with MAP. Ang-(1-7) levels were associated with changes in the microbiota. There were differences in the intestinal microbiota between control and AP mice. Ang-(1-7) attenuated intestinal microbiota dysbiosis in AP mice, reflecting in the increase in beneficial bacteria (Odoribacter and Butyricimonas) than AP, as well as pancreatic and intestinal injuries. Oral administration of Ang-(1-7) reversing AP-induced decreases in metabolisms: secondary bile acids, emodin, and naringenin. Ang-(1-7) may improve intestinal microbiota dysbiosis and modulate fecal metabolites in AP, thereby reducing the damage of AP.
急性胰腺炎（AP）是一种严重的健康问题，会导致肠道微生物群失调。血管紧张素（Ang）-（1-7）在 AP 中的肠道屏障中发挥保护作用，但它对肠道微生物群的影响尚不清楚。为了研究 Ang-（1-7）对 AP 引起的肠道微生物群紊乱和代谢物的影响。我们收集了 31 名入院后 48 小时内的 AP 患者的血液和粪便样本，其中 11 名患有轻度 AP（MAP），14 名患有中度严重 AP（MSAP），6 名患有严重 AP（SAP）。小鼠分为四组：对照组、AP 组、尾静脉注射 Ang-（1-7）的 AP 组和口服 Ang-（1-7）的 AP 组。AP 后 12 小时收集小鼠样本。采用 Schmidt 和 Chiu 评分分析胰腺和肠道组织病理学评分。通过 16S rDNA 测序和非靶向代谢组学分析分别进行粪便微生物群和代谢物分析。在患者中，与 MAP 相比，SAP 中有益菌（Negativicutes）的丰度降低，而致病菌（Clostridium bolteae 和 Ruminococcus gnavus）增加。Ang-（1-7）水平与微生物群的变化相关。对照组和 AP 小鼠的肠道微生物群存在差异。Ang-（1-7）减轻了 AP 小鼠的肠道微生物群失调，反映在有益菌（Odoribacter 和 Butyricimonas）的增加，而胰腺和肠道损伤减轻。口服 Ang-（1-7）逆转了 AP 引起的代谢物减少：次级胆汁酸、大黄素和柚皮素。Ang-（1-7）可能通过改善 AP 中的肠道微生物群失调和调节粪便代谢物来减轻 AP 的损害。
