Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice
Abstract Rotavirus (RV) remains a significant cause of infantile morbidity and mortality, while oral RV vaccines offer inconsistent protection. This study investigates whether gut microbiota influence immune responses to orally and intramuscularly (IM) administered RV strains. Using murine models, w...
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| Format: | Article |
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Nature Portfolio
2025-04-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01126-9 |
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| author | Zhenda Shi Sung-Sil Moon Jun Zou Yanling Wang Noopur Bhatnagar Vu L. Ngo Xiaoqian Wang Houping Wang Theresa K. Bessey Jennifer J. Hull Yuhuan Wang Sang-Moo Kang Andrew T. Gewirtz Baoming Jiang |
| author_facet | Zhenda Shi Sung-Sil Moon Jun Zou Yanling Wang Noopur Bhatnagar Vu L. Ngo Xiaoqian Wang Houping Wang Theresa K. Bessey Jennifer J. Hull Yuhuan Wang Sang-Moo Kang Andrew T. Gewirtz Baoming Jiang |
| author_sort | Zhenda Shi |
| collection | DOAJ |
| description | Abstract Rotavirus (RV) remains a significant cause of infantile morbidity and mortality, while oral RV vaccines offer inconsistent protection. This study investigates whether gut microbiota influence immune responses to orally and intramuscularly (IM) administered RV strains. Using murine models, we identified microbiota constituents, including segmented filamentous bacteria, reducing oral RV infection and RV antibody generation. Such blockade of RV-induced responses was associated with elevated expression of intestinal Reg3β and Reg3γ and was recapitulated by intraperitoneal administration of cognate recombinant proteins. IM administration following oral RV inoculations enhanced antibody production and defense against RV challenge. We further showed microbiota composition also influenced the efficacy of a single IM RV inoculation. Antibiotic-induced microbiota depletion boosted IM RV efficacy in poorly responding animals. Such enhancement of IM RV-induced immunity appeared to be associated with increased expression of serum RANTES and Eotaxin. The phenotype was recapitulated by directly adjuvating these chemokines to the IM inoculum. |
| format | Article |
| id | doaj-art-18f5e41730ce4d08abb2d6196d5dfa57 |
| institution | OA Journals |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-18f5e41730ce4d08abb2d6196d5dfa572025-08-20T02:24:26ZengNature Portfolionpj Vaccines2059-01052025-04-0110111010.1038/s41541-025-01126-9Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in miceZhenda Shi0Sung-Sil Moon1Jun Zou2Yanling Wang3Noopur Bhatnagar4Vu L. Ngo5Xiaoqian Wang6Houping Wang7Theresa K. Bessey8Jennifer J. Hull9Yuhuan Wang10Sang-Moo Kang11Andrew T. Gewirtz12Baoming Jiang13Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionInstitute for Biomedical Sciences, Georgia State UniversityInstitute for Biomedical Sciences, Georgia State UniversityInstitute for Biomedical Sciences, Georgia State UniversityInstitute for Biomedical Sciences, Georgia State UniversityDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionInstitute for Biomedical Sciences, Georgia State UniversityInstitute for Biomedical Sciences, Georgia State UniversityDivision of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and PreventionAbstract Rotavirus (RV) remains a significant cause of infantile morbidity and mortality, while oral RV vaccines offer inconsistent protection. This study investigates whether gut microbiota influence immune responses to orally and intramuscularly (IM) administered RV strains. Using murine models, we identified microbiota constituents, including segmented filamentous bacteria, reducing oral RV infection and RV antibody generation. Such blockade of RV-induced responses was associated with elevated expression of intestinal Reg3β and Reg3γ and was recapitulated by intraperitoneal administration of cognate recombinant proteins. IM administration following oral RV inoculations enhanced antibody production and defense against RV challenge. We further showed microbiota composition also influenced the efficacy of a single IM RV inoculation. Antibiotic-induced microbiota depletion boosted IM RV efficacy in poorly responding animals. Such enhancement of IM RV-induced immunity appeared to be associated with increased expression of serum RANTES and Eotaxin. The phenotype was recapitulated by directly adjuvating these chemokines to the IM inoculum.https://doi.org/10.1038/s41541-025-01126-9 |
| spellingShingle | Zhenda Shi Sung-Sil Moon Jun Zou Yanling Wang Noopur Bhatnagar Vu L. Ngo Xiaoqian Wang Houping Wang Theresa K. Bessey Jennifer J. Hull Yuhuan Wang Sang-Moo Kang Andrew T. Gewirtz Baoming Jiang Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice npj Vaccines |
| title | Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice |
| title_full | Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice |
| title_fullStr | Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice |
| title_full_unstemmed | Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice |
| title_short | Gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice |
| title_sort | gut microbiota modulate immune responses to orally and parenterally administered rotavirus in mice |
| url | https://doi.org/10.1038/s41541-025-01126-9 |
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