Chengdong Wu, Yan Mi, Jixuan Song, Min Zhang, Caili Wang
{"title":"人脐带间充质干细胞对糖尿病肾病大鼠肠道微生物群的调节作用。","authors":"Chengdong Wu, Yan Mi, Jixuan Song, Min Zhang, Caili Wang","doi":"10.30498/ijb.2025.472772.3975","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation is increasingly recognized as a key factor in the progression of diabetic kidney disease (DKD). By discovering that the regulation of gut microbiota plays an important role in diabetic kidney disease, human umbilical cord mesenchymal stem cells (HU-MSCs) explore the mechanism of fibrosis in diabetic kidney disease through the regulation of chronic inflammation, providing new clinical insights for the prediction, diagnosis, and treatment of diabetic kidney disease.</p><p><strong>Objectives: </strong>This study explores the regulatory effects of HU-MSCs on gut microbiota and their protective role on the intestinal barrier in diabetic nephropathy rats.</p><p><strong>Material and method: </strong>Diabetic kidney disease (DKD) was induced in SD rats via intraperitoneal injection of streptozotocin. Three groups were established: control group, diabetic kidney disease (DKD) group, and treatment group (DKD+HU-MSCs) (10 rats each). After diabetic kidney disease (DKD) modeling, rats in the treatment group (DKD+HU-MSCs) received 2×10<sup>6</sup> HU-MSCs via tail vein injection weekly for four weeks. Blood, urine, kidney, and colon tissues were collected post-treatment. Pathological changes were observed microscopically; immunohistochemistry detected tight junction proteins ZO-1 and Occludin in colon tissues. DiR-labeled HU-MSCs distribution was assessed with <i>in vivo</i> imaging, and immunohistochemistry evaluated human mesenchymal stem cell markers CD44 and CD90. Fecal samples underwent metagenomic sequencing for gut microbiota analysis.</p><p><strong>Results: </strong>HU-MSCs transplantation significantly reduced Blood Urea Nitrogen (BUN), Serum Creatinine (SCr), and 24-hour urinary protein levels (all P < 0.05) and improved renal pathology. Markers CD44 and CD90 were present in DKD rat colon tissues. Tight junction proteins Occludin and ZO-1 were decreased in DKD rats but increased following HU-MSCs treatment. Metagenomic analysis showed enhanced abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) with HU-MSCs. Urinary protein was positively correlated with Prevotella and negatively with Ligilactobacillus (p < 0.05).</p><p><strong>Conclusions: </strong>HU-MSCs may improve intestinal barrier function in diabetic kidney disease (DKD) rats by restoring gut microbiota structure and increasing intestinal tight junction proteins, offering a potential pathway for enhancing renal function.</p>","PeriodicalId":14492,"journal":{"name":"Iranian Journal of Biotechnology","volume":"23 1","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128948/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Regulatory Effect of Human Umbilical Cord Mesenchymal Stem Cells on the Gut Microbiota in Diabetic Nephropathy Rats.\",\"authors\":\"Chengdong Wu, Yan Mi, Jixuan Song, Min Zhang, Caili Wang\",\"doi\":\"10.30498/ijb.2025.472772.3975\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chronic inflammation is increasingly recognized as a key factor in the progression of diabetic kidney disease (DKD). By discovering that the regulation of gut microbiota plays an important role in diabetic kidney disease, human umbilical cord mesenchymal stem cells (HU-MSCs) explore the mechanism of fibrosis in diabetic kidney disease through the regulation of chronic inflammation, providing new clinical insights for the prediction, diagnosis, and treatment of diabetic kidney disease.</p><p><strong>Objectives: </strong>This study explores the regulatory effects of HU-MSCs on gut microbiota and their protective role on the intestinal barrier in diabetic nephropathy rats.</p><p><strong>Material and method: </strong>Diabetic kidney disease (DKD) was induced in SD rats via intraperitoneal injection of streptozotocin. Three groups were established: control group, diabetic kidney disease (DKD) group, and treatment group (DKD+HU-MSCs) (10 rats each). After diabetic kidney disease (DKD) modeling, rats in the treatment group (DKD+HU-MSCs) received 2×10<sup>6</sup> HU-MSCs via tail vein injection weekly for four weeks. Blood, urine, kidney, and colon tissues were collected post-treatment. Pathological changes were observed microscopically; immunohistochemistry detected tight junction proteins ZO-1 and Occludin in colon tissues. DiR-labeled HU-MSCs distribution was assessed with <i>in vivo</i> imaging, and immunohistochemistry evaluated human mesenchymal stem cell markers CD44 and CD90. Fecal samples underwent metagenomic sequencing for gut microbiota analysis.</p><p><strong>Results: </strong>HU-MSCs transplantation significantly reduced Blood Urea Nitrogen (BUN), Serum Creatinine (SCr), and 24-hour urinary protein levels (all P < 0.05) and improved renal pathology. Markers CD44 and CD90 were present in DKD rat colon tissues. Tight junction proteins Occludin and ZO-1 were decreased in DKD rats but increased following HU-MSCs treatment. Metagenomic analysis showed enhanced abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) with HU-MSCs. Urinary protein was positively correlated with Prevotella and negatively with Ligilactobacillus (p < 0.05).</p><p><strong>Conclusions: </strong>HU-MSCs may improve intestinal barrier function in diabetic kidney disease (DKD) rats by restoring gut microbiota structure and increasing intestinal tight junction proteins, offering a potential pathway for enhancing renal function.</p>\",\"PeriodicalId\":14492,\"journal\":{\"name\":\"Iranian Journal of Biotechnology\",\"volume\":\"23 1\",\"pages\":\"\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128948/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Iranian Journal of Biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.30498/ijb.2025.472772.3975\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Iranian Journal of Biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.30498/ijb.2025.472772.3975","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
The Regulatory Effect of Human Umbilical Cord Mesenchymal Stem Cells on the Gut Microbiota in Diabetic Nephropathy Rats.
Background: Chronic inflammation is increasingly recognized as a key factor in the progression of diabetic kidney disease (DKD). By discovering that the regulation of gut microbiota plays an important role in diabetic kidney disease, human umbilical cord mesenchymal stem cells (HU-MSCs) explore the mechanism of fibrosis in diabetic kidney disease through the regulation of chronic inflammation, providing new clinical insights for the prediction, diagnosis, and treatment of diabetic kidney disease.
Objectives: This study explores the regulatory effects of HU-MSCs on gut microbiota and their protective role on the intestinal barrier in diabetic nephropathy rats.
Material and method: Diabetic kidney disease (DKD) was induced in SD rats via intraperitoneal injection of streptozotocin. Three groups were established: control group, diabetic kidney disease (DKD) group, and treatment group (DKD+HU-MSCs) (10 rats each). After diabetic kidney disease (DKD) modeling, rats in the treatment group (DKD+HU-MSCs) received 2×106 HU-MSCs via tail vein injection weekly for four weeks. Blood, urine, kidney, and colon tissues were collected post-treatment. Pathological changes were observed microscopically; immunohistochemistry detected tight junction proteins ZO-1 and Occludin in colon tissues. DiR-labeled HU-MSCs distribution was assessed with in vivo imaging, and immunohistochemistry evaluated human mesenchymal stem cell markers CD44 and CD90. Fecal samples underwent metagenomic sequencing for gut microbiota analysis.
Results: HU-MSCs transplantation significantly reduced Blood Urea Nitrogen (BUN), Serum Creatinine (SCr), and 24-hour urinary protein levels (all P < 0.05) and improved renal pathology. Markers CD44 and CD90 were present in DKD rat colon tissues. Tight junction proteins Occludin and ZO-1 were decreased in DKD rats but increased following HU-MSCs treatment. Metagenomic analysis showed enhanced abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) with HU-MSCs. Urinary protein was positively correlated with Prevotella and negatively with Ligilactobacillus (p < 0.05).
Conclusions: HU-MSCs may improve intestinal barrier function in diabetic kidney disease (DKD) rats by restoring gut microbiota structure and increasing intestinal tight junction proteins, offering a potential pathway for enhancing renal function.
期刊介绍：
Iranian Journal of Biotechnology (IJB) is published quarterly by the National Institute of Genetic Engineering and Biotechnology. IJB publishes original scientific research papers in the broad area of Biotechnology such as, Agriculture, Animal and Marine Sciences, Basic Sciences, Bioinformatics, Biosafety and Bioethics, Environment, Industry and Mining and Medical Sciences.
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