Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function
IntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolite...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1096565/full |
| _version_ | 1797844949195030528 |
|---|---|
| author | Hong Ki Min Hyun Sik Na Hyun Sik Na Hyun Sik Na Hyun Sik Na JooYeon Jhun JooYeon Jhun JooYeon Jhun Seon-Yeong Lee Seon-Yeong Lee Sun Shim Choi Go Eun Park Jeong Su Lee Jeong Su Lee Jeong Su Lee Jeong Su Lee In Gyu Um In Gyu Um In Gyu Um In Gyu Um Seung Yoon Lee Seung Yoon Lee Seung Yoon Lee Seung Yoon Lee Hochan Seo Tae-Seop Shin Yoon-Keun Kim Jennifer Jooha Lee Seung-Ki Kwok Mi-La Cho Mi-La Cho Mi-La Cho Mi-La Cho Sung-Hwan Park |
| author_facet | Hong Ki Min Hyun Sik Na Hyun Sik Na Hyun Sik Na Hyun Sik Na JooYeon Jhun JooYeon Jhun JooYeon Jhun Seon-Yeong Lee Seon-Yeong Lee Sun Shim Choi Go Eun Park Jeong Su Lee Jeong Su Lee Jeong Su Lee Jeong Su Lee In Gyu Um In Gyu Um In Gyu Um In Gyu Um Seung Yoon Lee Seung Yoon Lee Seung Yoon Lee Seung Yoon Lee Hochan Seo Tae-Seop Shin Yoon-Keun Kim Jennifer Jooha Lee Seung-Ki Kwok Mi-La Cho Mi-La Cho Mi-La Cho Mi-La Cho Sung-Hwan Park |
| author_sort | Hong Ki Min |
| collection | DOAJ |
| description | IntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis.MethodUsing 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes.ResultsAs a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, Bacteroides and Streptococcus were more abundant in axSpA patients than in HCs, whereas Faecalibacterium (F). prausnitzii, a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether F. prausnitzii was associated with health conditions by inoculating F. prausnitzii (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4+ T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4+ T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4+ IL-17A+ T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by F. prausnitzii inoculation. Butyrate reduced CD4+ IL-17A+ T cell differentiation and osteoclastogenesis.DiscussionWe found that CD4+ IL-17A+ T cell polarization was reduced, when F. prausnitzii or butyrate were introduced into curdlan-induced SpA mice or CD4+ T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly F. prausnitzii, may be associated with axSpA pathogenesis. |
| first_indexed | 2024-04-09T17:30:39Z |
| format | Article |
| id | doaj.art-a6a26fd7283f46ab95db75404de0a658 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T17:30:39Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a6a26fd7283f46ab95db75404de0a6582023-04-18T06:12:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.10965651096565Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating functionHong Ki Min0Hyun Sik Na1Hyun Sik Na2Hyun Sik Na3Hyun Sik Na4JooYeon Jhun5JooYeon Jhun6JooYeon Jhun7Seon-Yeong Lee8Seon-Yeong Lee9Sun Shim Choi10Go Eun Park11Jeong Su Lee12Jeong Su Lee13Jeong Su Lee14Jeong Su Lee15In Gyu Um16In Gyu Um17In Gyu Um18In Gyu Um19Seung Yoon Lee20Seung Yoon Lee21Seung Yoon Lee22Seung Yoon Lee23Hochan Seo24Tae-Seop Shin25Yoon-Keun Kim26Jennifer Jooha Lee27Seung-Ki Kwok28Mi-La Cho29Mi-La Cho30Mi-La Cho31Mi-La Cho32Sung-Hwan Park33Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDivision of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Republic of KoreaDivision of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaMD Healthcare Inc., Seoul, Republic of KoreaMD Healthcare Inc., Seoul, Republic of KoreaMD Healthcare Inc., Seoul, Republic of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaThe Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDivision of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaIntroductionDysbiosis is an environmental factor that affects the induction of axial spondyloarthritis (axSpA) pathogenesis. In the present study, we investigated differences in the gut microbiota of patients with axSpA and revealed an association between specific gut microbiota and their metabolites, and SpA pathogenesis.MethodUsing 16S rRNA sequencing data derived from feces samples of 33 axSpA patients and 20 healthy controls (HCs), we examined the compositions of their gut microbiomes.ResultsAs a result, axSpA patients were found to have decreased α-diversity compared to HCs, indicating that axSpA patients have less diverse microbiomes. In particular, at the species level, Bacteroides and Streptococcus were more abundant in axSpA patients than in HCs, whereas Faecalibacterium (F). prausnitzii, a butyrate-producing bacteria, was more abundant in HCs. Thus, we decided to investigate whether F. prausnitzii was associated with health conditions by inoculating F. prausnitzii (0.1, 1, and 10 μg/mL) or by administrating butyrate (0.5 mM) into CD4+ T cells derived from axSpA patients. The levels of IL-17A and IL-10 in the CD4+ T cell culture media were then measured. We also assessed osteoclast formation by administrating butyrate to the axSpA-derived peripheral blood mononuclear cells. The CD4+ IL-17A+ T cell differentiation, IL-17A levels were decreased, whereas IL-10 was increased by F. prausnitzii inoculation. Butyrate reduced CD4+ IL-17A+ T cell differentiation and osteoclastogenesis.DiscussionWe found that CD4+ IL-17A+ T cell polarization was reduced, when F. prausnitzii or butyrate were introduced into curdlan-induced SpA mice or CD4+ T cells of axSpA patient. Consistently, butyrate treatment was associated with the reduction of arthritis scores and inflammation levels in SpA mice. Taken together, we concluded that the reduced abundance of butyrate-producing microbes, particularly F. prausnitzii, may be associated with axSpA pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1096565/fullspondyloarthropathiesdysbiosisgastrointestinal microbiomeFaecalibacterium prausnitziibutyrate |
| spellingShingle | Hong Ki Min Hyun Sik Na Hyun Sik Na Hyun Sik Na Hyun Sik Na JooYeon Jhun JooYeon Jhun JooYeon Jhun Seon-Yeong Lee Seon-Yeong Lee Sun Shim Choi Go Eun Park Jeong Su Lee Jeong Su Lee Jeong Su Lee Jeong Su Lee In Gyu Um In Gyu Um In Gyu Um In Gyu Um Seung Yoon Lee Seung Yoon Lee Seung Yoon Lee Seung Yoon Lee Hochan Seo Tae-Seop Shin Yoon-Keun Kim Jennifer Jooha Lee Seung-Ki Kwok Mi-La Cho Mi-La Cho Mi-La Cho Mi-La Cho Sung-Hwan Park Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function Frontiers in Immunology spondyloarthropathies dysbiosis gastrointestinal microbiome Faecalibacterium prausnitzii butyrate |
| title | Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function |
| title_full | Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function |
| title_fullStr | Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function |
| title_full_unstemmed | Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function |
| title_short | Identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome-derived butyrate with immune-modulating function |
| title_sort | identification of gut dysbiosis in axial spondyloarthritis patients and improvement of experimental ankylosing spondyloarthritis by microbiome derived butyrate with immune modulating function |
| topic | spondyloarthropathies dysbiosis gastrointestinal microbiome Faecalibacterium prausnitzii butyrate |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1096565/full |
| work_keys_str_mv | AT hongkimin identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT hyunsikna identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT hyunsikna identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT hyunsikna identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT hyunsikna identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jooyeonjhun identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jooyeonjhun identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jooyeonjhun identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seonyeonglee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seonyeonglee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT sunshimchoi identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT goeunpark identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jeongsulee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jeongsulee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jeongsulee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jeongsulee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT ingyuum identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT ingyuum identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT ingyuum identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT ingyuum identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seungyoonlee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seungyoonlee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seungyoonlee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seungyoonlee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT hochanseo identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT taeseopshin identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT yoonkeunkim identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT jenniferjoohalee identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT seungkikwok identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT milacho identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT milacho identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT milacho identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT milacho identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction AT sunghwanpark identificationofgutdysbiosisinaxialspondyloarthritispatientsandimprovementofexperimentalankylosingspondyloarthritisbymicrobiomederivedbutyratewithimmunemodulatingfunction |