Biomedical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
Chronic Kidney Disease Prevention in Northeastern Thailand, Khon Kaen University, Khon Kaen, Thailand.
PLoS One. 2024 May 30;19(5):e0301907. doi: 10.1371/journal.pone.0301907. eCollection 2024.
Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated the effects of a combination of O. viverrini infection and HFF diet on kidney pathology via changes in the gut microbiome and host proteome in hamsters.
METHODOLOGY/PRINCIPAL FINDINGS: Twenty animals were divided into four groups; 1) fed a normal diet not infected with O. viverrini (normal group), 2) fed an HFF diet and not infected with O. viverrini (HFF), 3) fed a normal diet and infected with O. viverrini (Ov), and 4) fed an HFF diet and infected with O. viverrini (HFFOv). DNA was extracted from fecal samples and the V3-V4 region of the bacterial 16S rRNA gene sequenced on an Illumina MiSeq sequencing platform. In addition, LC/MS-MS analysis was done. Histopathological studies and biochemical assays were also conducted. The results indicated that the HFFOv group exhibited the most severe kidney injury, manifested as elevated KIM-1 expression and accumulation of fibrosis in kidney tissue. The microbiome of the HFFOv group was more diverse than in the HFF group: there were increased numbers of Ruminococcaceae, Lachnospiraceae, Desulfovibrionaceae and Akkermansiaceae, but fewer Eggerthellaceae. In total, 243 host proteins were identified across all groups. Analysis using STITCH predicted that host proteome changes may lead to leaking of the gut, allowing molecules such as soluble CD14 and p-cresol to pass through to promote kidney disease. In addition, differential expression of TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Tab2, involving renal inflammation and injury) are predicted to be associated with kidney disease.
CONCLUSIONS/SIGNIFICANCE: The combination of HFF diet and O. viverrini infection may promote kidney injury through alterations in the gut microbiome and host proteome. This knowledge may suggest an effective strategy to prevent kidney disease beyond the early stages.
华支睾吸虫（O. viverrini，Ov）感染和高脂肪高果糖（HFF）饮食会加重肝、肾疾病。在这里，我们通过研究感染华支睾吸虫和 HFF 饮食对仓鼠肠道微生物群和宿主蛋白质组变化对肾脏病理的影响，来探讨两者结合对肾脏疾病的影响。
方法/主要发现：将 20 只动物分为四组：1）正常饮食未感染华支睾吸虫（正常组），2）HFF 饮食未感染华支睾吸虫（HFF），3）正常饮食感染华支睾吸虫（Ov），4）HFF 饮食感染华支睾吸虫（HFFOv）。从粪便样本中提取 DNA，并在 Illumina MiSeq 测序平台上对细菌 16S rRNA 基因的 V3-V4 区进行测序。此外，还进行了 LC/MS-MS 分析。进行了组织病理学研究和生化测定。结果表明，HFFOv 组表现出最严重的肾损伤，表现为肾组织中 KIM-1 表达升高和纤维化积聚。HFFOv 组的微生物组比 HFF 组更为多样化：厚壁菌门、毛螺菌科、脱硫弧菌科和阿克曼氏菌科的数量增加，而 Eggerthellaceae 的数量减少。总共鉴定了所有组的 243 种宿主蛋白。使用 STITCH 进行的分析表明，宿主蛋白质组的变化可能导致肠道渗漏，使可溶性 CD14 和 p-邻甲酚等分子通过，从而促进肾脏疾病。此外，TGF-β激活激酶 1 和丝裂原活化蛋白激酶激酶激酶 7 结合蛋白 2（Tab2，涉及肾脏炎症和损伤）的差异表达被预测与肾脏疾病有关。
结论/意义：HFF 饮食和华支睾吸虫感染的结合可能通过肠道微生物群和宿主蛋白质组的改变来促进肾脏损伤。这些知识可能提示了一种预防肾脏疾病的有效策略，而不仅仅是在早期阶段。
