Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials
Asthma, a chronic airway inflammatory disease driven by complex immune dysregulation, still remains a global health challenge despite its advances in biologic therapies. Butyrate, a major short-chain fatty acids (SCFAs) produced by intestinal microorganisms in the fermentation of dietary fiber, has...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1639606/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849242697052717056 |
|---|---|
| author | Chao Liu Zhu Zeng Mei Chen Yuwei Fan Qingsong Huang Jianying Wu |
| author_facet | Chao Liu Zhu Zeng Mei Chen Yuwei Fan Qingsong Huang Jianying Wu |
| author_sort | Chao Liu |
| collection | DOAJ |
| description | Asthma, a chronic airway inflammatory disease driven by complex immune dysregulation, still remains a global health challenge despite its advances in biologic therapies. Butyrate, a major short-chain fatty acids (SCFAs) produced by intestinal microorganisms in the fermentation of dietary fiber, has recently garnered considerable attention for its multifaceted roles in maintaining immune homeostasis and modulating airway inflammation. This review summarizes the molecular mechanisms and recent advances by which butyrate alleviates asthmatic inflammation, including suppression of excessive activation of type 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, inhibition of mast cells (MCs) degranulation, epigenetic modulation, regulation of receptor-mediated signaling pathways, and interactions along the gut–lung axis. We integrate current knowledge of butyrate’s multidimensional immunoregulatory network in asthma and propose a dual approach—via microbiota-based interventions and targeted modulation of the immune microenvironment—to potentially overcome the limitations of conventional corticosteroid therapies. Despite its promising prospects, its clinical translation still faces many challenges, especially in airway specific delivery, improved bioavailability, and long-term safety. Innovative strategies, including nano-carrier engineering and targeted probiotic preparations are expected to improve their bioavailability and tissue specificity. Future research should focus on clarifying the dose-response relationship, long-term safety, and establishing individualized treatment stratification based on patients’ microbiota-metabolic characteristics. |
| format | Article |
| id | doaj-art-c8608d30e85e47a0bf0fbba126e7180b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-c8608d30e85e47a0bf0fbba126e7180b2025-08-20T03:59:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16396061639606Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentialsChao Liu0Zhu Zeng1Mei Chen2Yuwei Fan3Qingsong Huang4Jianying Wu5Department of Integrated Traditional Chinese and Western Clinical Medicine, School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Integrated Traditional Chinese and Western Clinical Medicine, School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaAsthma, a chronic airway inflammatory disease driven by complex immune dysregulation, still remains a global health challenge despite its advances in biologic therapies. Butyrate, a major short-chain fatty acids (SCFAs) produced by intestinal microorganisms in the fermentation of dietary fiber, has recently garnered considerable attention for its multifaceted roles in maintaining immune homeostasis and modulating airway inflammation. This review summarizes the molecular mechanisms and recent advances by which butyrate alleviates asthmatic inflammation, including suppression of excessive activation of type 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, inhibition of mast cells (MCs) degranulation, epigenetic modulation, regulation of receptor-mediated signaling pathways, and interactions along the gut–lung axis. We integrate current knowledge of butyrate’s multidimensional immunoregulatory network in asthma and propose a dual approach—via microbiota-based interventions and targeted modulation of the immune microenvironment—to potentially overcome the limitations of conventional corticosteroid therapies. Despite its promising prospects, its clinical translation still faces many challenges, especially in airway specific delivery, improved bioavailability, and long-term safety. Innovative strategies, including nano-carrier engineering and targeted probiotic preparations are expected to improve their bioavailability and tissue specificity. Future research should focus on clarifying the dose-response relationship, long-term safety, and establishing individualized treatment stratification based on patients’ microbiota-metabolic characteristics.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1639606/fullbutyratetype 2 innate lymphoid cellshistone deacetylaseshort chain fatty acidsimmunity |
| spellingShingle | Chao Liu Zhu Zeng Mei Chen Yuwei Fan Qingsong Huang Jianying Wu Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials Frontiers in Immunology butyrate type 2 innate lymphoid cells histone deacetylase short chain fatty acids immunity |
| title | Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials |
| title_full | Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials |
| title_fullStr | Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials |
| title_full_unstemmed | Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials |
| title_short | Immunomodulatory roles of butyrate in asthma: mechanisms and therapeutic potentials |
| title_sort | immunomodulatory roles of butyrate in asthma mechanisms and therapeutic potentials |
| topic | butyrate type 2 innate lymphoid cells histone deacetylase short chain fatty acids immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1639606/full |
| work_keys_str_mv | AT chaoliu immunomodulatoryrolesofbutyrateinasthmamechanismsandtherapeuticpotentials AT zhuzeng immunomodulatoryrolesofbutyrateinasthmamechanismsandtherapeuticpotentials AT meichen immunomodulatoryrolesofbutyrateinasthmamechanismsandtherapeuticpotentials AT yuweifan immunomodulatoryrolesofbutyrateinasthmamechanismsandtherapeuticpotentials AT qingsonghuang immunomodulatoryrolesofbutyrateinasthmamechanismsandtherapeuticpotentials AT jianyingwu immunomodulatoryrolesofbutyrateinasthmamechanismsandtherapeuticpotentials |