Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation
Abstract Tissue-dwelling helminths affect billions of people around the world. They are potent manipulators of the host immune system, prominently by promoting regulatory T cells (Tregs) and are generally associated with a modified host gut microbiome. However, the role of the gut microbiota in the...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-06-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-023-00410-7 |
| _version_ | 1797795774870847488 |
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| author | Yugui Wang Aijiang Guo Yang Zou Wenjie Mu Shengying Zhang Zhiqi Shi Zhongli Liu Xuepeng Cai Xing-Quan Zhu Shuai Wang |
| author_facet | Yugui Wang Aijiang Guo Yang Zou Wenjie Mu Shengying Zhang Zhiqi Shi Zhongli Liu Xuepeng Cai Xing-Quan Zhu Shuai Wang |
| author_sort | Yugui Wang |
| collection | DOAJ |
| description | Abstract Tissue-dwelling helminths affect billions of people around the world. They are potent manipulators of the host immune system, prominently by promoting regulatory T cells (Tregs) and are generally associated with a modified host gut microbiome. However, the role of the gut microbiota in the immunomodulatory processes for these non-intestinal parasites is still unclear. In the present study, we used an extra-intestinal cestode helminth model-larval Echinococcus multilocularis to explore the tripartite partnership (host-helminth-bacteria) in the context of regulating colonic Tregs in Balb/c mice. We showed that larval E. multilocularis infection in the peritoneal cavity attenuated colitis in Balb/c mice and induced a significant expansion of colonic Foxp3+ Treg populations. Fecal microbiota depletion and transplantation experiments showed that the gut microbiota contributed to increasing Tregs after the helminth infection. Shotgun metagenomic and metabolic analyses revealed that the gut microbiome structure after infection was significantly shifted with a remarkable increase of Lactobacillus reuteri and that the microbial metabolic capability was reprogrammed to produce more Treg cell regulator-short-chain fatty acids in feces. Furthermore, we also prove that the L. reuteri strain elevated in infected mice was sufficient to promote the colonic Treg frequency and its growth was potentially associated with T cell-dependent immunity in larval E. multilocularis infection. Collectively, these findings indicate that the extraintestinal helminth drives expansions of host colonic Tregs through the gut microbes. This study suggests that the gut microbiome serves as a critical component of anti-inflammation effects even for a therapy based on an extraintestinal helminth. |
| first_indexed | 2024-03-13T03:24:07Z |
| format | Article |
| id | doaj.art-55e6a2e0786344cba145a8d48d0e6e99 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-03-13T03:24:07Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-55e6a2e0786344cba145a8d48d0e6e992023-06-25T11:10:27ZengNature Portfolionpj Biofilms and Microbiomes2055-50082023-06-019111210.1038/s41522-023-00410-7Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulationYugui Wang0Aijiang Guo1Yang Zou2Wenjie Mu3Shengying Zhang4Zhiqi Shi5Zhongli Liu6Xuepeng Cai7Xing-Quan Zhu8Shuai Wang9College of Veterinary Medicine, Shanxi Agricultural UniversityState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesCollege of Veterinary Medicine, Shanxi Agricultural UniversityState Key Laboratory of Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural SciencesAbstract Tissue-dwelling helminths affect billions of people around the world. They are potent manipulators of the host immune system, prominently by promoting regulatory T cells (Tregs) and are generally associated with a modified host gut microbiome. However, the role of the gut microbiota in the immunomodulatory processes for these non-intestinal parasites is still unclear. In the present study, we used an extra-intestinal cestode helminth model-larval Echinococcus multilocularis to explore the tripartite partnership (host-helminth-bacteria) in the context of regulating colonic Tregs in Balb/c mice. We showed that larval E. multilocularis infection in the peritoneal cavity attenuated colitis in Balb/c mice and induced a significant expansion of colonic Foxp3+ Treg populations. Fecal microbiota depletion and transplantation experiments showed that the gut microbiota contributed to increasing Tregs after the helminth infection. Shotgun metagenomic and metabolic analyses revealed that the gut microbiome structure after infection was significantly shifted with a remarkable increase of Lactobacillus reuteri and that the microbial metabolic capability was reprogrammed to produce more Treg cell regulator-short-chain fatty acids in feces. Furthermore, we also prove that the L. reuteri strain elevated in infected mice was sufficient to promote the colonic Treg frequency and its growth was potentially associated with T cell-dependent immunity in larval E. multilocularis infection. Collectively, these findings indicate that the extraintestinal helminth drives expansions of host colonic Tregs through the gut microbes. This study suggests that the gut microbiome serves as a critical component of anti-inflammation effects even for a therapy based on an extraintestinal helminth.https://doi.org/10.1038/s41522-023-00410-7 |
| spellingShingle | Yugui Wang Aijiang Guo Yang Zou Wenjie Mu Shengying Zhang Zhiqi Shi Zhongli Liu Xuepeng Cai Xing-Quan Zhu Shuai Wang Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation npj Biofilms and Microbiomes |
| title | Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation |
| title_full | Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation |
| title_fullStr | Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation |
| title_full_unstemmed | Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation |
| title_short | Interaction between tissue-dwelling helminth and the gut microbiota drives mucosal immunoregulation |
| title_sort | interaction between tissue dwelling helminth and the gut microbiota drives mucosal immunoregulation |
| url | https://doi.org/10.1038/s41522-023-00410-7 |
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