Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure
IntroductionHeart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many dis...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1255971/full |
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| author | Jian-Zheng Yang Kai-Kai Zhang Hong-Wu Shen Hong-Wu Shen Yi Liu Xiu-Wen Li Li-Jian Chen Jia-Li Liu Jia-Hao Li Dong Zhao Qi Wang Chu-Song Zhou |
| author_facet | Jian-Zheng Yang Kai-Kai Zhang Hong-Wu Shen Hong-Wu Shen Yi Liu Xiu-Wen Li Li-Jian Chen Jia-Li Liu Jia-Hao Li Dong Zhao Qi Wang Chu-Song Zhou |
| author_sort | Jian-Zheng Yang |
| collection | DOAJ |
| description | IntroductionHeart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated.MethodsIn this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1−/−) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF.ResultsCompared with the WT-ISO group, Sigmar1−/− aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1−/− exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar−/−-ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues.ConclusionTaken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation. |
| first_indexed | 2024-03-12T11:49:12Z |
| format | Article |
| id | doaj.art-fd460bb4f39f410ca154680560abda6f |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-12T11:49:12Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-fd460bb4f39f410ca154680560abda6f2023-08-31T11:52:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-08-011410.3389/fmicb.2023.12559711255971Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failureJian-Zheng Yang0Kai-Kai Zhang1Hong-Wu Shen2Hong-Wu Shen3Yi Liu4Xiu-Wen Li5Li-Jian Chen6Jia-Li Liu7Jia-Hao Li8Dong Zhao9Qi Wang10Chu-Song Zhou11Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaKey Laboratory of Evidence Science (China University of Political Science and Law), Ministry of Education, Beijing, ChinaSecurity Department, University of Electronic Science and Technology of China, Chengdu, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaKey Laboratory of Evidence Science (China University of Political Science and Law), Ministry of Education, Beijing, ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Spine Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaIntroductionHeart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated.MethodsIn this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1−/−) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF.ResultsCompared with the WT-ISO group, Sigmar1−/− aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1−/− exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar−/−-ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues.ConclusionTaken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1255971/fullheart failuresigma-1 receptorgut microbiotauntargeted metabolomicstranscriptomicsinflammation |
| spellingShingle | Jian-Zheng Yang Kai-Kai Zhang Hong-Wu Shen Hong-Wu Shen Yi Liu Xiu-Wen Li Li-Jian Chen Jia-Li Liu Jia-Hao Li Dong Zhao Qi Wang Chu-Song Zhou Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure Frontiers in Microbiology heart failure sigma-1 receptor gut microbiota untargeted metabolomics transcriptomics inflammation |
| title | Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure |
| title_full | Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure |
| title_fullStr | Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure |
| title_full_unstemmed | Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure |
| title_short | Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure |
| title_sort | sigma 1 receptor knockout disturbs gut microbiota remodels serum metabolome and exacerbates isoprenaline induced heart failure |
| topic | heart failure sigma-1 receptor gut microbiota untargeted metabolomics transcriptomics inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1255971/full |
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