Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study
BackgroundAccumulating evidence suggests that the gut microbiota and its metabolites may be involved in autoimmune hypothyroidism. However, the causal association between gut microbiota, metabolites and autoimmune hypothyroidism remains to be determined.MethodsInstrumental variables were screened fr...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213159/full |
| _version_ | 1827391210824663040 |
|---|---|
| author | Xue Liu Jie Yuan Shuai Liu Mulin Tang Xue Meng Xinhui Wang Yuchen Li Yuwei Chai Chunjia Kou Qingqing Yang Juyi Li Li Zhang Qingbo Guan Qingbo Guan Qingbo Guan Qingbo Guan Haiqing Zhang Haiqing Zhang Haiqing Zhang Haiqing Zhang |
| author_facet | Xue Liu Jie Yuan Shuai Liu Mulin Tang Xue Meng Xinhui Wang Yuchen Li Yuwei Chai Chunjia Kou Qingqing Yang Juyi Li Li Zhang Qingbo Guan Qingbo Guan Qingbo Guan Qingbo Guan Haiqing Zhang Haiqing Zhang Haiqing Zhang Haiqing Zhang |
| author_sort | Xue Liu |
| collection | DOAJ |
| description | BackgroundAccumulating evidence suggests that the gut microbiota and its metabolites may be involved in autoimmune hypothyroidism. However, the causal association between gut microbiota, metabolites and autoimmune hypothyroidism remains to be determined.MethodsInstrumental variables were screened from the GWAS datasets of 211 gut microbiota taxonomic groups, gut microbiota-derived metabolites, and autoimmune hypothyroidism. Univariable Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) were used to analyse the potential causal relationship between autoimmune hypothyroidism, these metabolites, or these microbiota. During the MR analysis, we alternated multiple MR methods with different model assumptions to assess the consistency and robustness of the findings: inverse variance weighted (IVW), weighted median, MR pleiotropy residual sum and outlier (MRPRESSO) and MR−Egger methods. Reverse MR analysis was performed to assess the possibility of reverse causality. Finally, enrichment analyses were used to investigate potential biofunctions.ResultsThe IVW results of univariable MR showed that the phyla Actinobacteria, genus DefluviitaleaceaeUCG011, genus Eggerthella, family Defluviitaleaceae, genus Subdoligranulum, genus RuminococcaceaeUCG011, and genus Intestinimonas were associated with autoimmune hypothyroidism. After FDR adjustment, the absence of a causal relationship between gut microbiota and autoimmune hypothyroidism (PFDR > 0.05) suggested a possible marginal association. The results on gut metabolites showed that N-(3-furoyl)glycine, pipecolate, phenylalanine, allantoin, indololactate and alanine were associated with autoimmune hypothyroidism. After FDR correction, only indololactate was associated with hypothyroidism (OR=1.592; 95% CI, 1.228-2.065; PFDR= 0.036). Family Defluviitaleaceae and genus DefluviitaleaceaeUCG011 were suggestively significant in the MVMR. The results of reverse MR analysis showed no reverse causality between autoimmune hypothyroidism and the identified gut microbiota. Enrichment analysis revealed that several key regulatory pathways were significantly enriched.ConclusionThis study supported that there were beneficial or detrimental causal effects of gut microbiota and its metabolites on autoimmune hypothyroidism risk, which provides more theoretical support for mechanistic research on the “thyroid–gut” axis. |
| first_indexed | 2024-03-08T17:06:26Z |
| format | Article |
| id | doaj.art-f3d980056f1e40f8bb81a4571b367d02 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T17:06:26Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f3d980056f1e40f8bb81a4571b367d022024-01-04T04:43:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.12131591213159Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization studyXue Liu0Jie Yuan1Shuai Liu2Mulin Tang3Xue Meng4Xinhui Wang5Yuchen Li6Yuwei Chai7Chunjia Kou8Qingqing Yang9Juyi Li10Li Zhang11Qingbo Guan12Qingbo Guan13Qingbo Guan14Qingbo Guan15Haiqing Zhang16Haiqing Zhang17Haiqing Zhang18Haiqing Zhang19Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaDepartment of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, ChinaKey Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaKey Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaDepartment of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaKey Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaShandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, ChinaInstitute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, ChinaDepartment of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaKey Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, ChinaShandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, ChinaInstitute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, ChinaBackgroundAccumulating evidence suggests that the gut microbiota and its metabolites may be involved in autoimmune hypothyroidism. However, the causal association between gut microbiota, metabolites and autoimmune hypothyroidism remains to be determined.MethodsInstrumental variables were screened from the GWAS datasets of 211 gut microbiota taxonomic groups, gut microbiota-derived metabolites, and autoimmune hypothyroidism. Univariable Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) were used to analyse the potential causal relationship between autoimmune hypothyroidism, these metabolites, or these microbiota. During the MR analysis, we alternated multiple MR methods with different model assumptions to assess the consistency and robustness of the findings: inverse variance weighted (IVW), weighted median, MR pleiotropy residual sum and outlier (MRPRESSO) and MR−Egger methods. Reverse MR analysis was performed to assess the possibility of reverse causality. Finally, enrichment analyses were used to investigate potential biofunctions.ResultsThe IVW results of univariable MR showed that the phyla Actinobacteria, genus DefluviitaleaceaeUCG011, genus Eggerthella, family Defluviitaleaceae, genus Subdoligranulum, genus RuminococcaceaeUCG011, and genus Intestinimonas were associated with autoimmune hypothyroidism. After FDR adjustment, the absence of a causal relationship between gut microbiota and autoimmune hypothyroidism (PFDR > 0.05) suggested a possible marginal association. The results on gut metabolites showed that N-(3-furoyl)glycine, pipecolate, phenylalanine, allantoin, indololactate and alanine were associated with autoimmune hypothyroidism. After FDR correction, only indololactate was associated with hypothyroidism (OR=1.592; 95% CI, 1.228-2.065; PFDR= 0.036). Family Defluviitaleaceae and genus DefluviitaleaceaeUCG011 were suggestively significant in the MVMR. The results of reverse MR analysis showed no reverse causality between autoimmune hypothyroidism and the identified gut microbiota. Enrichment analysis revealed that several key regulatory pathways were significantly enriched.ConclusionThis study supported that there were beneficial or detrimental causal effects of gut microbiota and its metabolites on autoimmune hypothyroidism risk, which provides more theoretical support for mechanistic research on the “thyroid–gut” axis.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213159/fullgut microbiotagut metabolitesautoimmune hypothyroidismmendelian randomizationthyroid-gut axis |
| spellingShingle | Xue Liu Jie Yuan Shuai Liu Mulin Tang Xue Meng Xinhui Wang Yuchen Li Yuwei Chai Chunjia Kou Qingqing Yang Juyi Li Li Zhang Qingbo Guan Qingbo Guan Qingbo Guan Qingbo Guan Haiqing Zhang Haiqing Zhang Haiqing Zhang Haiqing Zhang Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study Frontiers in Immunology gut microbiota gut metabolites autoimmune hypothyroidism mendelian randomization thyroid-gut axis |
| title | Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study |
| title_full | Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study |
| title_fullStr | Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study |
| title_full_unstemmed | Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study |
| title_short | Investigating causal associations among gut microbiota, metabolites and autoimmune hypothyroidism: a univariable and multivariable Mendelian randomization study |
| title_sort | investigating causal associations among gut microbiota metabolites and autoimmune hypothyroidism a univariable and multivariable mendelian randomization study |
| topic | gut microbiota gut metabolites autoimmune hypothyroidism mendelian randomization thyroid-gut axis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1213159/full |
| work_keys_str_mv | AT xueliu investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT jieyuan investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT shuailiu investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT mulintang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT xuemeng investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT xinhuiwang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT yuchenli investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT yuweichai investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT chunjiakou investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT qingqingyang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT juyili investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT lizhang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT qingboguan investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT qingboguan investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT qingboguan investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT qingboguan investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT haiqingzhang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT haiqingzhang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT haiqingzhang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy AT haiqingzhang investigatingcausalassociationsamonggutmicrobiotametabolitesandautoimmunehypothyroidismaunivariableandmultivariablemendelianrandomizationstudy |