Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice
Abstract Background Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; how...
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BMC
2025-04-01
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| Series: | Cellular & Molecular Biology Letters |
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| Online Access: | https://doi.org/10.1186/s11658-025-00716-8 |
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| author | Quanren Pan Fengbiao Guo Jiaxuan Chen Haimin Huang Yanyan Huang Shuzhen Liao Zengzhi Xiao Xi Wang Liuyong You Lawei Yang Xuemei Huang Haiyan Xiao Hua-Feng Liu Qingjun Pan |
| author_facet | Quanren Pan Fengbiao Guo Jiaxuan Chen Haimin Huang Yanyan Huang Shuzhen Liao Zengzhi Xiao Xi Wang Liuyong You Lawei Yang Xuemei Huang Haiyan Xiao Hua-Feng Liu Qingjun Pan |
| author_sort | Quanren Pan |
| collection | DOAJ |
| description | Abstract Background Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; however, the long-term efficacy and mechanisms of early hUC-MSC therapeutic benefits in SLE need further investigation. Methods Here, lupus-prone MRL/MpJ-Fas lpr (MRL/lpr) mice were divided into three groups: the control (Ctrl) group received saline injections, while the MSC and MSC-fecal microbiota transplantation (FMT) groups received early hUC-MSC transplants at weeks 6, 8, and 10. The MSC-FMT group also underwent FMT from the Ctrl group between weeks 9 and 13. Results Our results showed that early MSC treatment extended therapeutic effects up to 12 weeks, reducing autoantibodies, proinflammatory cytokines, B cells, and improving lupus nephritis. It also modulated the gut microbiota, increasing the abundance of beneficial bacteria, such as Lactobacillus johnsonii and Romboutsia ilealis, which led to higher levels of plasma tryptophan and butyrate metabolites. These metabolites activate the aryl hydrocarbon receptor (AHR), upregulate the Cyp1a1 and Cyp1b1 gene, enhance the zonula occludens 1 (ZO-1) protein, promote intestinal repair, and mitigate SLE progression. Notably, FMT from lupus mice significantly reversed hUC-MSC benefits, suggesting that the modulation of the gut microbiota plays a crucial role in the therapeutic response observed in MRL/lpr mice. Conclusions This research innovatively explores the early therapeutic window for MSCs in SLE, highlighting the partial mechanisms through which hUC-MSCs modulate the gut microbiota–tryptophan–AHR axis, thereby ameliorating SLE symptoms. Graphical Abstract |
| format | Article |
| id | doaj-art-5822634f4a1045d1828c2fcfa618bc97 |
| institution | OA Journals |
| issn | 1689-1392 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj-art-5822634f4a1045d1828c2fcfa618bc972025-08-20T02:17:56ZengBMCCellular & Molecular Biology Letters1689-13922025-04-0130112710.1186/s11658-025-00716-8Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr miceQuanren Pan0Fengbiao Guo1Jiaxuan Chen2Haimin Huang3Yanyan Huang4Shuzhen Liao5Zengzhi Xiao6Xi Wang7Liuyong You8Lawei Yang9Xuemei Huang10Haiyan Xiao11Hua-Feng Liu12Qingjun Pan13Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Clinical Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityDepartment of Anesthesiology, First People’s Hospital of FoshanDepartment of Cellular Biology and Anatomy, James and Jean Culver Vision Discovery Institute, Medical College of Georgia, Augusta UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityGuangdong Provincial Key Laboratory of Autophagy and Major Chronic Noncommunicable Diseases, Department of Nephrology, Affiliated Hospital of Guangdong Medical UniversityAbstract Background Systemic lupus erythematosus (SLE), influenced by gut microbiota dysbiosis, is characterized by autoimmune and inflammatory responses. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is an effective and safe treatment for refractory or severe SLE; however, the long-term efficacy and mechanisms of early hUC-MSC therapeutic benefits in SLE need further investigation. Methods Here, lupus-prone MRL/MpJ-Fas lpr (MRL/lpr) mice were divided into three groups: the control (Ctrl) group received saline injections, while the MSC and MSC-fecal microbiota transplantation (FMT) groups received early hUC-MSC transplants at weeks 6, 8, and 10. The MSC-FMT group also underwent FMT from the Ctrl group between weeks 9 and 13. Results Our results showed that early MSC treatment extended therapeutic effects up to 12 weeks, reducing autoantibodies, proinflammatory cytokines, B cells, and improving lupus nephritis. It also modulated the gut microbiota, increasing the abundance of beneficial bacteria, such as Lactobacillus johnsonii and Romboutsia ilealis, which led to higher levels of plasma tryptophan and butyrate metabolites. These metabolites activate the aryl hydrocarbon receptor (AHR), upregulate the Cyp1a1 and Cyp1b1 gene, enhance the zonula occludens 1 (ZO-1) protein, promote intestinal repair, and mitigate SLE progression. Notably, FMT from lupus mice significantly reversed hUC-MSC benefits, suggesting that the modulation of the gut microbiota plays a crucial role in the therapeutic response observed in MRL/lpr mice. Conclusions This research innovatively explores the early therapeutic window for MSCs in SLE, highlighting the partial mechanisms through which hUC-MSCs modulate the gut microbiota–tryptophan–AHR axis, thereby ameliorating SLE symptoms. Graphical Abstracthttps://doi.org/10.1186/s11658-025-00716-8Mesenchymal stem cellsSystemic lupus erythematosusGut microbiotaTryptophan metabolismButanoate metabolismAryl hydrocarbon receptor |
| spellingShingle | Quanren Pan Fengbiao Guo Jiaxuan Chen Haimin Huang Yanyan Huang Shuzhen Liao Zengzhi Xiao Xi Wang Liuyong You Lawei Yang Xuemei Huang Haiyan Xiao Hua-Feng Liu Qingjun Pan Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice Cellular & Molecular Biology Letters Mesenchymal stem cells Systemic lupus erythematosus Gut microbiota Tryptophan metabolism Butanoate metabolism Aryl hydrocarbon receptor |
| title | Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice |
| title_full | Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice |
| title_fullStr | Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice |
| title_full_unstemmed | Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice |
| title_short | Exploring the role of gut microbiota modulation in the long-term therapeutic benefits of early MSC transplantation in MRL/lpr mice |
| title_sort | exploring the role of gut microbiota modulation in the long term therapeutic benefits of early msc transplantation in mrl lpr mice |
| topic | Mesenchymal stem cells Systemic lupus erythematosus Gut microbiota Tryptophan metabolism Butanoate metabolism Aryl hydrocarbon receptor |
| url | https://doi.org/10.1186/s11658-025-00716-8 |
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