Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Department of General Internal Medicine, Fukui-ken Saiseikai Hospital, Fukui, Japan.
Front Cell Infect Microbiol. 2024 Apr 8;14:1371429. doi: 10.3389/fcimb.2024.1371429. eCollection 2024.
Achieving sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) reduces all-cause mortality. However, the mechanisms and risk factors for liver fibrosis and portal hypertension post-SVR remain incompletely understood. In the gut-liver axis, mucosa-associated microbiota (MAM) substantially influence immune and metabolic functions, displaying spatial heterogeneity at the anatomical intestinal site. We analyzed MAM composition and function to isolate the locoregional MAM involved in chronic liver disease progression in HCV post-SVR patients.
We collected MAM samples from three intestinal sites (terminal ileum, ascending colon, and sigmoid colon) via brushing during colonoscopy in 23 HCV post-SVR patients and 25 individuals without liver disease (controls). The 16S rRNA of bacterial DNA in specimens collected with a brush and in feces was sequenced. The molecular expression of intestinal tissues and hepatic tissues were evaluated by quantitative real-time PCR.
In the post-SVR group, the microbial β-diversity of MAM, especially in the ascending colon, differed from the control group and was associated with liver fibrosis progression. In PICRUSt analysis, MAM in the ascending colon in the liver cirrhosis (LC) group showed compromised functions associated with the intestinal barrier and bile acid production, and FGF19 expression was markedly decreased in the terminal ileum biopsy tissue in the LC group. At the genus level, six short-chain fatty acid (SCFA)-producing bacterial genera, , , , , , and were reduced in the ascending colon of post-SVR LC patients.
In patients of HCV post-SVR, we identified the association between the degree of liver fibrosis and dysbiosis of mucosa-associated SCFA-producing bacterial genera that may be related to intestinal barrier and bile acid production in the ascending colon.
慢性丙型肝炎病毒（HCV）感染者实现持续病毒学应答（SVR）可降低全因死亡率。然而，SVR 后肝纤维化和门静脉高压的机制和危险因素仍不完全清楚。在肠道-肝脏轴中，黏膜相关微生物群（MAM）极大地影响免疫和代谢功能，在解剖学肠道部位显示出空间异质性。我们分析了 MAM 的组成和功能，以分离 SVR 后 HCV 患者慢性肝病进展中涉及的局部 MAM。
我们通过结肠镜检查在 23 例 SVR 后 HCV 患者和 25 例无肝病的个体（对照组）的三个肠道部位（回肠末端、升结肠和乙状结肠）通过刷洗收集 MAM 样本。用刷子收集的标本和粪便中的细菌 DNA 的 16S rRNA 进行测序。通过定量实时 PCR 评估肠道组织和肝组织的分子表达。
在 SVR 后组中，MAM 的微生物 β 多样性，特别是在升结肠，与对照组不同，与肝纤维化进展相关。在 PICRUSt 分析中，肝硬化（LC）组升结肠的 MAM 显示与肠道屏障和胆汁酸生成相关的功能受损，LC 组回肠末端活检组织中 FGF19 的表达明显降低。在属水平上，六个产生短链脂肪酸（SCFA）的细菌属， ， ， ， ， 和 在 SVR 后 LC 患者的升结肠中减少。
在 SVR 后 HCV 患者中，我们确定了肝纤维化程度与黏膜相关产生 SCFA 的细菌属失调之间的关联，这可能与升结肠的肠道屏障和胆汁酸生成有关。
