Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation
IntroductionInflammatory bowel diseases (IBDs) are associated with both immune abnormalities and dysbiosis, characterized by a loss of Faecalibacterium prausnitzii (F. prausnitzii). However, the reason for F. prausnitzii deficiency remains unclear.Methods16S rDNA sequencing and IgA enzyme-linked im...
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040774/full |
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| author | Kairuo Wang Kairuo Wang Yixuan Guo Yixuan Guo Yixuan Guo Yuanyuan Liu Yuanyuan Liu Yuanyuan Liu Xiao Cui Xiao Cui Xiao Cui Xiang Gu Xiang Gu Xiang Gu Lixiang Li Lixiang Li Lixiang Li Yanqing Li Yanqing Li Yanqing Li Ming Li Ming Li Ming Li Ming Li |
| author_facet | Kairuo Wang Kairuo Wang Yixuan Guo Yixuan Guo Yixuan Guo Yuanyuan Liu Yuanyuan Liu Yuanyuan Liu Xiao Cui Xiao Cui Xiao Cui Xiang Gu Xiang Gu Xiang Gu Lixiang Li Lixiang Li Lixiang Li Yanqing Li Yanqing Li Yanqing Li Ming Li Ming Li Ming Li Ming Li |
| author_sort | Kairuo Wang |
| collection | DOAJ |
| description | IntroductionInflammatory bowel diseases (IBDs) are associated with both immune abnormalities and dysbiosis, characterized by a loss of Faecalibacterium prausnitzii (F. prausnitzii). However, the reason for F. prausnitzii deficiency remains unclear.Methods16S rDNA sequencing and IgA enzyme-linked immunosorbent assay (ELISA) were applied to identify bacterial community and IgA changes in ulcerative colitis (UC) patients. Forced immunization with F. prausnitzii in rabbits was conducted. To screen for potential IgA-reactive proteins in F. prausnitzii lysates, we performed western blotting and mass spectrometry analyses. Pyruvate: ferredoxin oxidoreductase (PFOR) was cloned and purified, then the immunoreactivity of PFOR was verified in peripheral blood mononuclear cells (PBMCs) through PCR, ELISpot assay and single-cell sequencing (scRNA-seq). Finally, the UC fecal dysbiosis was re-analyzed in the context of the phylogenetic tree of PFOR.ResultsF. prausnitzii was underrepresented in UC patients with elevated F. prausnitzii-reactive IgA in the fecal supernatant. Forced immunization with F. prausnitzii in rabbits led to high interferon-γ (IFN-γ) transcription in the colon, along with beta diversity disturbance and intestinal inflammation. PFOR was identified as an IgA-binding antigen of F. prausnitzii and the immunoreactivity was validated in PBMCs, which showed elevated expression of inflammatory cytokines. The scRNA-seq revealed enhanced signals in both T regulatory cells (Tregs) and monocytes after PFOR incubation. Furthermore, phylogenetic analysis revealed that PFOR was a common but conserved protein among the gut bacteria.DiscussionOur results collectively suggest that PFOR is a bioactive protein in the immune system and may contribute to host-microbial crosstalk. Conserved but bioactive microbial proteins, such as PFOR, warrant more attention in future host-microbial interaction studies. |
| first_indexed | 2024-04-13T07:04:53Z |
| format | Article |
| id | doaj.art-daf05ed4788949f5b21d2b7e257ba21d |
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| language | English |
| last_indexed | 2024-04-13T07:04:53Z |
| publishDate | 2022-12-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-daf05ed4788949f5b21d2b7e257ba21d2022-12-22T02:57:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10407741040774Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammationKairuo Wang0Kairuo Wang1Yixuan Guo2Yixuan Guo3Yixuan Guo4Yuanyuan Liu5Yuanyuan Liu6Yuanyuan Liu7Xiao Cui8Xiao Cui9Xiao Cui10Xiang Gu11Xiang Gu12Xiang Gu13Lixiang Li14Lixiang Li15Lixiang Li16Yanqing Li17Yanqing Li18Yanqing Li19Ming Li20Ming Li21Ming Li22Ming Li23Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaLaboratory of Translational Gastroenterology, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaRobot Engineering Laboratory for Precise Diagnosis and Therapy of Gastrointestinal Tumor, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaShandong Provincial Clinical Research Center for digestive disease, Qilu Hospital, Shandong University, Jinan, Shandong, ChinaIntroductionInflammatory bowel diseases (IBDs) are associated with both immune abnormalities and dysbiosis, characterized by a loss of Faecalibacterium prausnitzii (F. prausnitzii). However, the reason for F. prausnitzii deficiency remains unclear.Methods16S rDNA sequencing and IgA enzyme-linked immunosorbent assay (ELISA) were applied to identify bacterial community and IgA changes in ulcerative colitis (UC) patients. Forced immunization with F. prausnitzii in rabbits was conducted. To screen for potential IgA-reactive proteins in F. prausnitzii lysates, we performed western blotting and mass spectrometry analyses. Pyruvate: ferredoxin oxidoreductase (PFOR) was cloned and purified, then the immunoreactivity of PFOR was verified in peripheral blood mononuclear cells (PBMCs) through PCR, ELISpot assay and single-cell sequencing (scRNA-seq). Finally, the UC fecal dysbiosis was re-analyzed in the context of the phylogenetic tree of PFOR.ResultsF. prausnitzii was underrepresented in UC patients with elevated F. prausnitzii-reactive IgA in the fecal supernatant. Forced immunization with F. prausnitzii in rabbits led to high interferon-γ (IFN-γ) transcription in the colon, along with beta diversity disturbance and intestinal inflammation. PFOR was identified as an IgA-binding antigen of F. prausnitzii and the immunoreactivity was validated in PBMCs, which showed elevated expression of inflammatory cytokines. The scRNA-seq revealed enhanced signals in both T regulatory cells (Tregs) and monocytes after PFOR incubation. Furthermore, phylogenetic analysis revealed that PFOR was a common but conserved protein among the gut bacteria.DiscussionOur results collectively suggest that PFOR is a bioactive protein in the immune system and may contribute to host-microbial crosstalk. Conserved but bioactive microbial proteins, such as PFOR, warrant more attention in future host-microbial interaction studies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040774/fullulcerative colitisFaecalibacterium prausnitziipyruvate: ferredoxin (flavodoxin) oxidoreductaseimmunoglobin Adysbiosis |
| spellingShingle | Kairuo Wang Kairuo Wang Yixuan Guo Yixuan Guo Yixuan Guo Yuanyuan Liu Yuanyuan Liu Yuanyuan Liu Xiao Cui Xiao Cui Xiao Cui Xiang Gu Xiang Gu Xiang Gu Lixiang Li Lixiang Li Lixiang Li Yanqing Li Yanqing Li Yanqing Li Ming Li Ming Li Ming Li Ming Li Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation Frontiers in Immunology ulcerative colitis Faecalibacterium prausnitzii pyruvate: ferredoxin (flavodoxin) oxidoreductase immunoglobin A dysbiosis |
| title | Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation |
| title_full | Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation |
| title_fullStr | Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation |
| title_full_unstemmed | Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation |
| title_short | Pyruvate: Ferredoxin oxidoreductase is involved in IgA-related microbiota dysbiosis and intestinal inflammation |
| title_sort | pyruvate ferredoxin oxidoreductase is involved in iga related microbiota dysbiosis and intestinal inflammation |
| topic | ulcerative colitis Faecalibacterium prausnitzii pyruvate: ferredoxin (flavodoxin) oxidoreductase immunoglobin A dysbiosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040774/full |
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