State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
Appl Microbiol Biotechnol. 2019 Dec;103(23-24):9673-9686. doi: 10.1007/s00253-019-10211-8. Epub 2019 Nov 12.
The liver is an important digestive gland, and acute liver failure results in high mortality. Probiotics are considered potential adjuvant therapies for liver disease. This study aimed to investigate the beneficial effects of Lactobacillus helveticus R0052 on acute liver injury and the underlying mechanisms. Sprague-Dawley rats were gavaged with L. helveticus R0052 suspensions (3 × 10 CFU) for 1 week. Subsequently, acute liver injury was induced by intraperitoneal D-galactosamine injection on the eighth day. After 24 h, samples (blood, liver, ileum, faeces) were collected and assessed for histological injury, inflammation, intestinal barrier, gut microbiome and metabolome. L. helveticus R0052 alleviated aminotransferase, bilirubin and total bile acid elevation and histological hepatic injuries. Additionally, L. helveticus R0052 exhibited anti-inflammatory properties by downregulating Toll-like receptors, tumour necrosis factor-α and nuclear factor-κb transcription in liver samples and decreasing proinflammatory cytokine plasma concentrations. Additionally, L. helveticus R0052 ameliorated intestinal abnormalities and regulated Toll-like receptors, claudin2 and mucin3 gene transcription in the intestine. These effects were associated with gut microbiome and metabolome modulation by L. helveticus R0052. Probiotic pretreatment enriched Lactobacillus and Bacteroides and depleted Flavonifractor and Acetatifactor in the gut microbiome. Meanwhile, L. helveticus R0052 improved carbohydrate and fatty acid metabolism and reduced lithocholic acid levels. These results indicate that L. helveticus R0052 is promising for alleviating acute liver injury and provide new insights regarding the correlations among the microbiome, the metabolome, the intestinal barrier and liver disease.
肝脏是重要的消化腺，急性肝衰竭导致高死亡率。益生菌被认为是肝脏疾病的潜在辅助治疗方法。本研究旨在探讨瑞士乳杆菌 R0052 对急性肝损伤的有益作用及其潜在机制。Sprague-Dawley 大鼠连续 1 周灌胃瑞士乳杆菌 R0052 悬浮液（3×10 CFU）。第 8 天腹腔注射 D-半乳糖胺诱导急性肝损伤，24 h 后收集血液、肝脏、回肠、粪便样本，评估组织学损伤、炎症、肠道屏障、肠道微生物组和代谢组。瑞士乳杆菌 R0052 可减轻血清转氨酶、胆红素和总胆汁酸升高以及肝组织学损伤。此外，瑞士乳杆菌 R0052 通过下调肝组织 Toll 样受体、肿瘤坏死因子-α和核因子-κb 转录和降低促炎细胞因子血浆浓度发挥抗炎作用。此外，瑞士乳杆菌 R0052 可改善肠道异常，调节肠道 Toll 样受体、闭合蛋白 2 和粘蛋白 3 基因转录。这些作用与瑞士乳杆菌 R0052 调节肠道微生物组和代谢组有关。益生菌预处理可使肠道微生物组中乳杆菌属和拟杆菌属富集，黄杆菌属和乙酸杆菌属减少。同时，瑞士乳杆菌 R0052 可改善碳水化合物和脂肪酸代谢，降低石胆酸水平。这些结果表明瑞士乳杆菌 R0052 有望缓解急性肝损伤，并为肠道微生物组、代谢组、肠道屏障和肝脏疾病之间的相关性提供新的见解。
