Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral-gut and gut-oral axes through bidirectional Mendelian randomization.
Mendelian randomization
gut microbiome
gut-oral axis
oral-gut axis
periodontitis
Journal
Journal of clinical periodontology
ISSN: 1600-051X
Titre abrégé: J Clin Periodontol
Pays: United States
ID NLM: 0425123
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
revised:
05
11
2023
received:
29
04
2023
accepted:
07
11
2023
medline:
29
11
2023
pubmed:
29
11
2023
entrez:
28
11
2023
Statut:
aheadofprint
Résumé
This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis. We used genetic instruments from the genome-wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q-test was performed to detect heterogeneity. The MR-Egger regression intercept and MR pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to test potential horizontal pleiotropy. Leave-one-out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta-analysis. We confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014. The demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut-oral and oral-gut axes.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : the Natural Science Foundation Project of Chongqing, China
ID : CSTB2022NSCQ-MSX0084
Organisme : National Natural Science Foundation of China
ID : 81700982
Organisme : the Chongqing Medical Reserve Talent Studio for Young People
ID : ZQNYXGDRCGZS2019004
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Aas, J. A., Paster, B. J., Stokes, L. N., Olsen, I., & Dewhirst, F. E. (2005). Defining the normal bacterial flora of the oral cavity. Journal of Clinical Microbiology, 43(11), 5721-5732.
Aggor, F. E., Bertolini, M., Zhou, C., Taylor, T. C., Abbott, D. A., Musgrove, J., Bruno, V. M., Hand, T. W., & Gaffen, S. L. (2022). A gut-oral microbiome-driven axis controls oropharyngeal candidiasis through retinoic acid. JCI Insight, 7(18), e160348.
Atarashi, K., Suda, W., Luo, C., Kawaguchi, T., Motoo, I., Narushima, S., Kiguchi, Y., Yasuma, K., Watanabe, E., Tanoue, T., Thaiss, C. A., Sato, M., Toyooka, K., Said, H. S., Yamagami, H., Rice, S. A., Gevers, D., Johnson, R. C., Segre, J. A., … Honda, K. (2017). Ectopic colonization of oral bacteria in the intestine drives T(H)1 cell induction and inflammation. Science, 358(6361), 359-365.
Balduzzi, S., Rücker, G., & Schwarzer, G. (2019). How to perform a meta-analysis with R: A practical tutorial. Evidence-Based Mental Health, 22(4), 153-160.
Bao, J., Li, L., Zhang, Y., Wang, M., Chen, F., Ge, S., Chen, B., & Yan, F. (2022). Periodontitis may induce gut microbiota dysbiosis via salivary microbiota. International Journal of Oral Science, 14(1), 32.
Baumeister, S. E., Freuer, D., Baurecht, H., Reckelkamm, S. L., Ehmke, B., Holtfreter, B., & Nolde, M. (2022). Understanding the consequences of educational inequalities on periodontitis: A Mendelian randomization study. Journal of Clinical Periodontology, 49(3), 200-209.
Baumeister, S. E., Freuer, D., Nolde, M., Kocher, T., Baurecht, H., Khazaei, Y., Ehmke, B., & Holtfreter, B. (2021). Testing the association between tobacco smoking, alcohol consumption, and risk of periodontitis: A Mendelian randomization study. Journal of Clinical Periodontology, 48(11), 1414-1420.
Ben, E., Matthew, L., Tessa, A., Yi, L., Peter, M., Jon, H., Phil, B., Tom, P., Valeriia, H., George Davey, S., Jie, Z., Philip, H., Tom, R. G., & Gibran, H. (2020). The MRC IEU OpenGWAS data infrastructure. bioRxiv, 2020.08.10.244293.
Bernabe, E., Marcenes, W., Hernandez, C. R., Bailey, J., Abreu, L. G., Alipour, V., Amini, S., Arabloo, J., Arefi, Z., Arora, A., Ayanore, M. A., Bärnighausen, T. W., Bijani, A., Cho, D. Y., Chu, D. T., Crowe, C. S., Demoz, G. T., Demsie, D. G., Dibaji Forooshani, Z. S., . . . Kassebaum, N. J. (2020). Global, regional, and national levels and trends in burden of oral conditions from 1990 to 2017: A systematic analysis for the global burden of disease 2017 study. Journal of Dental Research, 99(4), 362-373.
Bowden, J., Davey Smith, G., Haycock, P. C., & Burgess, S. (2016). Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genetic Epidemiology, 40(4), 304-314.
Burgess, S., Davey Smith, G., Davies, N. M., Dudbridge, F., Gill, D., Glymour, M. M., Hartwig, F. P., Holmes, M. V., Minelli, C., Relton, C. L., & Theodoratou, E. (2019). Guidelines for performing Mendelian randomization investigations. Wellcome Open Research, 4, 186.
Burgess, S., & Thompson, S. G. (2015). Multivariable Mendelian randomization: The use of pleiotropic genetic variants to estimate causal effects. American Journal of Epidemiology, 181(4), 251-260.
Burgess, S., & Thompson, S. G. (2017). Interpreting findings from Mendelian randomization using the MR-Egger method. European Journal of Epidemiology, 32(5), 377-389.
Caton, J. G., Armitage, G., Berglundh, T., Chapple, I. L. C., Jepsen, S., Kornman, K. S., Mealey, B. L., Papapanou, P. N., Sanz, M., & Tonetti, M. S. (2018). A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. Journal of Clinical Periodontology, 45(Suppl 20), S1-s8.
Chen, L., Yang, H., Li, H., He, C., Yang, L., & Lv, G. (2022). Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study. Hepatology, 75(4), 785-796.
Chen, S. Y., Weng, M. H., Li, Z. Y., Wang, G. Y., & Yen, G. C. (2022). Protective effects of camellia and olive oils against cognitive impairment via gut microbiota-brain communication in rats. Food & Function, 13(13), 7168-7180.
Cobo, F., Franco-Acosta, A., Lara-Oya, A., & Pérez-Carrasco, V. (2023). Bacteremia caused by Alistipes finegoldii in a patient with peritonitis. Enfermedades Infecciosas y Microbiología Clínica (English Ed), 41(2), 131-132.
Curtis, M. A., Diaz, P. I., & Van Dyke, T. E. (2020). The role of the microbiota in periodontal disease. Periodontology 2000, 83(1), 14-25.
De Maesschalck, C., Van Immerseel, F., Eeckhaut, V., De Baere, S., Cnockaert, M., Croubels, S., Haesebrouck, F., Ducatelle, R., & Vandamme, P. (2014). Faecalicoccus acidiformans gen. nov., sp. nov., isolated from the chicken caecum, and reclassification of Streptococcus pleomorphus (Barnes et al. 1977), Eubacterium biforme (Eggerth 1935) and Eubacterium cylindroides (Cato et al. 1974) as Faecalicoccus pleomorphus comb. nov., Holdemanella biformis gen. nov., comb. nov. and Faecalitalea cylindroides gen. nov., comb. nov., respectively, within the family Erysipelotrichaceae. International Journal of Systematic and Evolutionary Microbiology, 64(Pt 11), 3877-3884.
de Mello-Neto, J. M., Elangovan, G., Ervolino, E., Johnson, N. W., Gustafsson, A., & da Silva Figueredo, C. M. (2023). Higher expression of Th1/Th2-related cytokines in the intestine of Wistar rats with ligature-induced periodontitis. Journal of Periodontal Research, 58(3), 588-595.
Deeks, J. J., Higgins, J. P. T., Altman, D. G., & Cochrane Statistical Methods Group. (2019). Analysing data and undertaking meta-analyses. In Cochrane handbook for systematic reviews of interventions (pp. 241-284). John Wiley & Sons Ltd.
Donaldson, G. P., Lee, S. M., & Mazmanian, S. K. (2016). Gut biogeography of the bacterial microbiota. Nature Reviews. Microbiology, 14(1), 20-32.
Dong, J., Gong, Y., Chu, T., Wu, L., Li, S., Deng, H., Hu, R., & Wang, Y. (2022). Mendelian randomization highlights the causal association of obesity with periodontal diseases. Journal of Clinical Periodontology, 49(7), 662-671.
Fine, N., Chadwick, J. W., Sun, C., Parbhakar, K. K., Khoury, N., Barbour, A., Goldberg, M., Tenenbaum, H. C., & Glogauer, M. (2021). Periodontal inflammation primes the systemic innate immune response. Journal of Dental Research, 100(3), 318-325.
Frémont, M., Coomans, D., Massart, S., & de Meirleir, K. (2013). High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients. Anaerobe, 22, 50-56.
Fukui, H. (2017). Gut microbiome-based therapeutics in liver cirrhosis: Basic consideration for the next step. Journal of Clinical and Translational Hepatology, 5(3), 249-260.
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N. N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., … Ohno, H. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 504(7480), 446-450.
Gacesa, R., Kurilshikov, A., Vich Vila, A., Sinha, T., Klaassen, M. A. Y., Bolte, L. A., Andreu-Sánchez, S., Chen, L., Collij, V., Hu, S., Dekens, J. A. M., Lenters, V. C., Björk, J. R., Swarte, J. C., Swertz, M. A., Jansen, B. H., Gelderloos-Arends, J., Jankipersadsing, S., Hofker, M., … Weersma, R. K. (2022). Environmental factors shaping the gut microbiome in a Dutch population. Nature, 604(7907), 732-739.
Gaffen, S. L., & Moutsopoulos, N. M. (2020). Regulation of host-microbe interactions at oral mucosal barriers by type 17 immunity. Science Immunology, 5(43), eaau4594.
Greco, M. F., Minelli, C., Sheehan, N. A., & Thompson, J. R. (2015). Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Statistics in Medicine, 34(21), 2926-2940.
Gu, Z. (2022). Complex heatmap visualization. iMeta, 1(3), e43.
Gu, Z., Gu, L., Eils, R., Schlesner, M., & Brors, B. (2014). circlize implements and enhances circular visualization in R. Bioinformatics, 30(19), 2811-2812.
Hajishengallis, G., Lamont, R. J., & Koo, H. (2023). Oral polymicrobial communities: Assembly, function, and impact on diseases. Cell Host & Microbe, 31(4), 528-538.
Harrington, C. R., Lucchini, S., Ridgway, K. P., Wegmann, U., Eaton, T. J., Hinton, J. C. D., Gasson, M. J., & Narbad, A. (2008). A short-oligonucleotide microarray that allows improved detection of gastrointestinal tract microbial communities. BMC Microbiology, 8, 195.
Hartwig, F. P., Davey Smith, G., & Bowden, J. (2017). Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. International Journal of Epidemiology, 46(6), 1985-1998.
Haskey, N., Estaki, M., Ye, J., Shim, R. K., Singh, S., Dieleman, L. A., Jacobson, K., & Gibson, D. L. (2023). A Mediterranean diet pattern improves intestinal inflammation concomitant with reshaping of the bacteriome in ulcerative colitis: A randomized controlled trial. Journal of Crohn's & Colitis, 17(10), 1569-1578.
Hemani, G., Bowden, J., & Davey Smith, G. (2018). Evaluating the potential role of pleiotropy in Mendelian randomization studies. Human Molecular Genetics, 27(R2), R195-r208.
Hemani, G., Tilling, K., & Davey Smith, G. (2017). Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genetics, 13(11), e1007081.
Hemani, G., Zheng, J., Elsworth, B., Wade, K. H., Haberland, V., Baird, D., Laurin, C., Burgess, S., Bowden, J., Langdon, R., Tan, V. Y., Yarmolinsky, J., Shihab, H. A., Timpson, N. J., Evans, D. M., Relton, C., Martin, R. M., Davey Smith, G., Gaunt, T. R., & Haycock, P. C. (2018). The MR-base platform supports systematic causal inference across the human phenome. eLife, 7, 7.
Jepsen, K., Falk, W., Brune, F., Cosgarea, R., Fimmers, R., Bekeredjian-Ding, I., & Jepsen, S. (2022). Prevalence and antibiotic susceptibility trends of selected Enterobacteriaceae, Enterococci, and Candida albicans in the subgingival microbiota of German periodontitis patients: A retrospective surveillance study. Antibiotics (Basel), 11(3), 385-397.
Kageyama, A., & Benno, Y. (2001). Rapid detection of human fecal Eubacterium species and related genera by nested PCR method. Microbiology and Immunology, 45(4), 315-318.
Kamat, M. A., Blackshaw, J. A., Young, R., Surendran, P., Burgess, S., Danesh, J., Butterworth, A. S., & Staley, J. R. (2019). PhenoScanner V2: An expanded tool for searching human genotype-phenotype associations. Bioinformatics, 35(22), 4851-4853.
Kato, T., Yamazaki, K., Nakajima, M., Date, Y., Kikuchi, J., Hase, K., Ohno, H., & Yamazaki, K. (2018). Oral Administration of Porphyromonas gingivalis alters the gut microbiome and serum metabolome. mSphere, 3(5), e00460.
Kawamoto, D., Borges, R., Ribeiro, R. A., de Souza, R. F., Amado, P. P. P., Saraiva, L., Horliana, A. C. R. T., Faveri, M., & Mayer, M. P. A. (2021). Oral dysbiosis in severe forms of periodontitis is associated with gut dysbiosis and correlated with salivary inflammatory mediators: A preliminary study. Frontiers in Oral Health, 2, 722495.
Kechagias, K. S., Kalliala, I., Bowden, S. J., Athanasiou, A., Paraskevaidi, M., Paraskevaidis, E., Dillner, J., Nieminen, P., Strander, B., Sasieni, P., Veroniki, A. A., & Kyrgiou, M. (2022). Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: Systematic review and meta-analysis. BMJ, 378, e070135.
Kitamoto, S., Nagao-Kitamoto, H., Jiao, Y., Gillilland, M. G., III, Hayashi, A., Imai, J., Sugihara, K., Miyoshi, M., Brazil, J. C., Kuffa, P., Hill, B. D., Rizvi, S. M., Wen, F., Bishu, S., Inohara, N., Eaton, K. A., Nusrat, A., Lei, Y. L., Giannobile, W. V., & Kamada, N. (2020). The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis. Cell, 182(2), 447-462.e14.
Kurilshikov, A., Medina-Gomez, C., Bacigalupe, R., Radjabzadeh, D., Wang, J., Demirkan, A., le Roy, C. I., Raygoza Garay, J. A., Finnicum, C. T., Liu, X., Zhernakova, D. V., Bonder, M. J., Hansen, T. H., Frost, F., Rühlemann, M. C., Turpin, W., Moon, J. Y., Kim, H. N., Lüll, K., … Zhernakova, A. (2021). Large-scale association analyses identify host factors influencing human gut microbiome composition. Nature Genetics, 53(2), 156-165.
Kurki, M. I., Karjalainen, J., Palta, P., Sipilä, T. P., Kristiansson, K., Donner, K. M., Reeve, M. P., Laivuori, H., Aavikko, M., Kaunisto, M. A., Loukola, A., Lahtela, E., Mattsson, H., Laiho, P., Della Briotta Parolo, P., Lehisto, A. A., Kanai, M., Mars, N., Rämö, J., … Palotie, A. (2023). FinnGen provides genetic insights from a well-phenotyped isolated population. Nature, 613(7944), 508-518.
Lam, G. A., Albarrak, H., McColl, C. J., Pizarro, A., Sanaka, H., Gomez-Nguyen, A., Cominelli, F., & Paes Batista da Silva, A. (2022). The oral-gut Axis: Periodontal diseases and gastrointestinal disorders. Inflammatory Bowel Diseases, 29, 1153-1164.
Lee, Y. H., Kalailingam, P., Delcour, J. A., Fogliano, V., & Thanabalu, T. (2023). Olive-derived antioxidant dietary fiber modulates gut microbiota composition and attenuates atopic dermatitis like inflammation in mice. Molecular Nutrition & Food Research, 67(10), e2200127.
Liu, K., Wu, P., Zou, J., Fan, H., Hu, H., Cheng, Y., He, F., Liu, J., & You, Z. (2022). Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis. Human Genetics, 142, 1139-1148.
Liu, X., Tong, X., Zou, Y., Lin, X., Zhao, H., Tian, L., Jie, Z., Wang, Q., Zhang, Z., Lu, H., Xiao, L., Qiu, X., Zi, J., Wang, R., Xu, X., Yang, H., Wang, J., Zong, Y., Liu, W., … Zhang, T. (2022). Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome. Nature Genetics, 54(1), 52-61.
Lord, J., Jermy, B., Green, R., Wong, A., Xu, J., Legido-Quigley, C., Dobson, R., Richards, M., & Proitsi, P. (2021). Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 118(16), e2009808118.
Louis, P., & Flint, H. J. (2017). Formation of propionate and butyrate by the human colonic microbiota. Environmental Microbiology, 19(1), 29-41.
Lourenςo, T. G. B., Spencer, S. J., Alm, E. J., & Colombo, A. P. V. (2018). Defining the gut microbiota in individuals with periodontal diseases: An exploratory study. Journal of Oral Microbiology, 10(1), 1487741.
Lun, H., Yang, W., Zhao, S., Jiang, M., Xu, M., Liu, F., & Wang, Y. (2019). Altered gut microbiota and microbial biomarkers associated with chronic kidney disease. Microbiology, 8(4), e00678.
Luo, S., Li, W., Li, Q., Zhang, M., Wang, X., Wu, S., & Li, Y. (2023). Causal effects of gut microbiota on the risk of periodontitis: A two-sample Mendelian randomization study. Frontiers in Cellular and Infection Microbiology, 13, 1160993.
Minguela, J. I., Aurrekoetxea, B., & Ferro, M. (2021). Peritonitis due to Alistipes finegoldii in a patient on peritoneal dialysis. Therapeutic Apheresis and Dialysis, 25(6), 1014-1016.
Nagao, J. I., Kishikawa, S., Tanaka, H., Toyonaga, K., Narita, Y., Negoro-Yasumatsu, K., Tasaki, S., Arita-Morioka, K. I., Nakayama, J., & Tanaka, Y. (2022). Pathobiont-responsive Th17 cells in gut-mouth axis provoke inflammatory oral disease and are modulated by intestinal microbiome. Cell Reports, 40(10), 111314.
Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T. (2017). Gut microbiota and IBD: Causation or correlation? Nature Reviews. Gastroenterology & Hepatology, 14(10), 573-584.
Nolde, M., Holtfreter, B., Kocher, T., Alayash, Z., Reckelkamm, S. L., Ehmke, B., Baurecht, H., & Baumeister, S. E. (2022). No bidirectional relationship between depression and periodontitis: A genetic correlation and Mendelian randomization study. Frontiers in Immunology, 13, 918404.
Page, R. C., & Eke, P. I. (2007). Case definitions for use in population-based surveillance of periodontitis. Journal of Periodontology, 78(7 Suppl), 1387-1399.
Parker, B. J., Wearsch, P. A., Veloo, A. C. M., & Rodriguez-Palacios, A. (2020). The genus Alistipes: Gut bacteria with emerging implications to inflammation, cancer, and mental health. Frontiers in Immunology, 11, 906.
Pujo, J., Petitfils, C., le Faouder, P., Eeckhaut, V., Payros, G., Maurel, S., Perez-Berezo, T., van Hul, M., Barreau, F., Blanpied, C., Chavanas, S., van Immerseel, F., Bertrand-Michel, J., Oswald, E., Knauf, C., Dietrich, G., Cani, P. D., & Cenac, N. (2021). Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis. Gut, 70(6), 1088-1097.
Sato, K., Yamazaki, K., Kato, T., Nakanishi, Y., Tsuzuno, T., Yokoji-Takeuchi, M., Yamada-Hara, M., Miura, N., Okuda, S., Ohno, H., & Yamazaki, K. (2021). Obesity-related gut microbiota aggravates alveolar bone destruction in experimental periodontitis through elevation of uric acid. MBio, 12(3), e0077121.
Saygun, I., Nizam, N., Keskiner, I., Bal, V., Kubar, A., Açıkel, C., Serdar, M., & Slots, J. (2011). Salivary infectious agents and periodontal disease status. Journal of Periodontal Research, 46(2), 235-239.
Scassellati, C., Marizzoni, M., Cattane, N., Lopizzo, N., Mombelli, E., Riva, M. A., & Cattaneo, A. (2021). The complex molecular picture of gut and oral microbiota-brain-depression system: What we know and what we need to know. Frontiers in Psychiatry, 12, 722335.
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003). Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11), 2498-2504.
She, Y. Y., Kong, X. B., Ge, Y. P., Liu, Z. Y., Chen, J. Y., Jiang, J. W., Jiang, H. B., & Fang, S. L. (2020). Periodontitis and inflammatory bowel disease: A meta-analysis. BMC Oral Health, 20(1), 67.
Shungin, D., Cornelis, M. C., Divaris, K., Holtfreter, B., Shaffer, J. R., Yu, Y. H., Barros, S. P., Beck, J. D., Biffar, R., Boerwinkle, E. A., Crout, R. J., Ganna, A., Hallmans, G., Hindy, G., Hu, F. B., Kraft, P., McNeil, D. W., Melander, O., Moss, K. L., … Franks, P. W. (2015). Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium. International Journal of Epidemiology, 44(2), 638-650.
Shungin, D., Haworth, S., Divaris, K., Agler, C. S., Kamatani, Y., Keun Lee, M., Grinde, K., Hindy, G., Alaraudanjoki, V., Pesonen, P., Teumer, A., Holtfreter, B., Sakaue, S., Hirata, J., Yu, Y. H., Ridker, P. M., Giulianini, F., Chasman, D. I., Magnusson, P. K. E., … Johansson, I. (2019). Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data. Nature Communications, 10(1), 2773.
Skrivankova, V. W., Richmond, R. C., Woolf, B. A. R., Yarmolinsky, J., Davies, N. M., Swanson, S. A., VanderWeele, T. J., Higgins, J. P. T., Timpson, N. J., Dimou, N., Langenberg, C., Golub, R. M., Loder, E. W., Gallo, V., Tybjaerg-Hansen, A., Davey Smith, G., Egger, M., & Richards, J. B. (2021). Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: The STROBE-MR statement. JAMA, 326(16), 1614-1621.
Sollis, E., Mosaku, A., Abid, A., Buniello, A., Cerezo, M., Gil, L., Groza, T., Güneş, O., Hall, P., Hayhurst, J., Ibrahim, A., Ji, Y., John, S., Lewis, E., MacArthur, J. A. L., McMahon, A., Osumi-Sutherland, D., Panoutsopoulou, K., Pendlington, Z., … Harris, L. W. (2023). The NHGRI-EBI GWAS catalog: Knowledgebase and deposition resource. Nucleic Acids Research, 51(D1), D977-d985.
Tao, J., An, Y., Xu, L., Wang, Y., Wang, C., Li, P., Li, M., Yan, D., Wang, M., Zhong, G., & Wu, M. (2023). The protective role of microbiota in the prevention of MPTP/P-induced Parkinson's disease by resveratrol. Food & Function, 14(10), 4647-4661.
Thanassoulis, G., & O'Donnell, C. J. (2009). Mendelian randomization: nature's randomized trial in the post-genome era. JAMA, 301(22), 2386-2388.
Tonetti, M. S., Greenwell, H., & Kornman, K. S. (2018). Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. Journal of Periodontology, 89(Suppl 1), S159-s172.
Tuganbaev, T., Yoshida, K., & Honda, K. (2022). The effects of oral microbiota on health. Science, 376(6596), 934-936.
Verbanck, M., Chen, C. Y., Neale, B., & do, R. (2018). Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nature Genetics, 50(5), 693-698.
Wang, Z., Li, S., Tan, D., Abudourexiti, W., Yu, Z., Zhang, T., Ding, C., & Gong, J. (2023). Association between inflammatory bowel disease and periodontitis: A bidirectional two-sample Mendelian randomization study. Journal of Clinical Periodontology, 50(6), 736-743.
Waters, J. L., & Ley, R. E. (2019). The human gut bacteria Christensenellaceae are widespread, heritable, and associated with health. BMC Biology, 17(1), 83.
Wickham, H. (2016). ggplot2: Elegant graphics for data analysis. Springer-Verlag.