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Gan G, Lu B, Zhang R, et al. Chronic apical periodontitis exacerbates atherosclerosis in apolipoprotein E-deficient mice and leads to changes in the diversity of gut microbiota. Int Endod J. 2021;doi: 10.1111/iej.13655.
Gan, G., Lu, B., Zhang, R., Luo, Y., Chen, S., Lei, H., Li, Y., Cai, Z., & Huang, X. (2021). Chronic apical periodontitis exacerbates atherosclerosis in apolipoprotein E-deficient mice and leads to changes in the diversity of gut microbiota. International endodontic journal, . https://doi.org/10.1111/iej.13655
Gan, Guowu, et al. "Chronic apical periodontitis exacerbates atherosclerosis in apolipoprotein E-deficient mice and leads to changes in the diversity of gut microbiota." International endodontic journal vol. (2021). doi: https://doi.org/10.1111/iej.13655
Gan G, Lu B, Zhang R, Luo Y, Chen S, Lei H, Li Y, Cai Z, Huang X. Chronic apical periodontitis exacerbates atherosclerosis in apolipoprotein E-deficient mice and leads to changes in the diversity of gut microbiota. Int Endod J. 2021 Oct 29; doi: 10.1111/iej.13655. Epub 2021 Oct 29. PMID: 34714545.
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Int Endod J. 2021 Oct 29; doi: 10.1111/iej.13655. Epub 2021 Oct 29.

Chronic apical periodontitis exacerbates atherosclerosis in apolipoprotein E-deficient mice and leads to changes in the diversity of gut microbiota.

International endodontic journal

Guowu Gan, Beibei Lu, Ren Zhang, Yufang Luo, Shuai Chen, Huaxiang Lei, Yijun Li, Zhiyu Cai, Xiaojing Huang

Affiliations

  1. Fujian Key Laboratory of Oral Diseases & Fujian Provincial Engineering Research Center of Oral Biomaterial & Stomatological Key lab of Fujian College and University, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
  2. Institute of Stomatology, Research Center of Dental and Craniofacial Implants, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
  3. Department of Stomatology, Fujian Medical University Union Hospital, Fuzhou, China.

PMID: 34714545 DOI: 10.1111/iej.13655

Abstract

AIM: To investigate the impact of chronic apical periodontitis (CAP) on atherosclerosis and gut microbiota by establishing a Porphyromonas gingivalis (P. gingivalis)-induced CAP in an apolipoprotein E-deficient (apoE

METHODOLOGY: Twenty-eight male apoE

RESULTS: CAP was observed in 98.2% of molars. A significant increase in atherosclerotic plaque formation in the aortic arches was found in the CAP groups (CAP: 2.001% ± 0.27%, control: 0.927% ± 0.22%, p = .005). No significant difference was observed between sevum level of HDL-C (CAP: 2.295 ± 0.31 mmol/L, Control: 3.037 ± 0.55 mmol/L, p = .264) or LDL-C (CAP: 17.066 ± 3.95 mmol/L, Control: 10.948 ± 1.69 mmol/L, p = .177) in CAP group and Control group. There were no significant differences in TG (CAP: 1.076 ± 0.08 mmol/L, control: 1.034 ± 0.13 mmol/L, p = .794) or TC (CAP: 6.372 ± 0.98 mmol/L, control: 6.679 ± 0.75 mmol/L, p = .72) levels between the two groups (p > .05). The alpha diversity was elevated in the CAP group. In terms of beta diversity, the CAP and control groups were clearly distinguished by the microbial community.

CONCLUSION: In a mouse experimental model, pulp infection with P. gingivalis -induced CAP, thus aggravating the development of atherosclerosis. Meanwhile, CAP increased alpha diversity and altered the beta diversity of the gut microbiota.

© 2021 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.

Keywords: Porphyromonas gingivalis ; animal model; atherosclerosis; chronic apical periodontitis; gut microbiota

References

  1. Aimetti, M., Romano, F. & Nessi, F. (2007) Microbiologic analysis of periodontal pockets and carotid atheromatous plaques in advanced chronic periodontitis patients. Journal of Periodontology, 78, 1718-1723. - PubMed
  2. An, G.K., Morse, D.E., Kunin, M., Goldberger, R.S. & Psoter, W.J. (2016) Association of radiographically diagnosed apical periodontitis and cardiovascular disease: a hospital records-based study. Journal of Endodontics, 42, 916-920. - PubMed
  3. Ao, M., Miyauchi, M., Inubushi, T., Kitagawa, M., Furusho, H., Ando, T. et al. (2014) Infection with Porphyromonas gingivalis exacerbates endothelial injury in obese mice. PLoS One, 9, e110519. - PubMed
  4. Arimatsu, K., Yamada, H., Miyazawa, H., Minagawa, T., Nakajima, M., Ryder, M.I. et al. (2014) Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Scientific Reports, 4, 4828. - PubMed
  5. Berlin-Broner, Y., Alexiou, M., Levin, L. & Febbraio, M. (2020) Characterization of a mouse model to study the relationship between apical periodontitis and atherosclerosis. International Endodontic Journal, 53, 812-823. - PubMed
  6. Berlin-Broner, Y., Febbraio, M. & Levin, L. (2017) Apical periodontitis and atherosclerosis: is there a link? Review of the literature and potential mechanism of linkage. Quintessence International, 48, 527-534. - PubMed
  7. Beverly, J.K. & Budoff, M.J. (2020) Atherosclerosis: pathophysiology of insulin resistance, hyperglycemia, hyperlipidemia, and inflammation. Journal of Diabetes, 12, 102-104. - PubMed
  8. Bokulich, N.A., Kaehler, B.D., Rideout, J.R., Dillon, M., Bolyen, E., Knight, R. et al. (2018) Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2's q2-feature-classifier plugin. Microbiome, 6, 90. - PubMed
  9. Brandsma, E., Kloosterhuis, N.J., Koster, M., Dekker, D.C., Gijbels, M.J.J., van der Velden, S. et al. (2019) A proinflammatory gut microbiota increases systemic inflammation and accelerates atherosclerosis. Circulation Research, 124, 94-100. - PubMed
  10. Brown, P.M., Kennedy, D.J., Morton, R.E. & Febbraio, M. (2015) CD36/SR-B2-TLR2 dependent pathways enhance Porphyromonas gingivalis mediated atherosclerosis in the Ldlr KO mouse model. PLoS One, 10, e0125126. - PubMed
  11. Bui, F.Q., Almeida-da-Silva, C.L.C., Huynh, B., Trinh, A., Liu, J., Woodward, J. et al. (2019) Association between periodontal pathogens and systemic disease. Biomedical Journal, 42, 27-35. - PubMed
  12. Callahan, B.J., McMurdie, P.J., Rosen, M.J., Han, A.W., Johnson, A.J. & Holmes, S.P. (2016) DADA2: High-resolution sample inference from Illumina amplicon data. Nature Methods, 13, 581-583. - PubMed
  13. Campbell, L.A. & Rosenfeld, M.E. (2015) Infection and atherosclerosis development. Archives of Medical Research, 46, 339-350. - PubMed
  14. Centa, M., Ketelhuth, D.F.J., Malin, S. & Gistera, A. (2019) Quantification of atherosclerosis in mice. Journal of Visualized Experiments, 59828. - PubMed
  15. Chan, Y.K., Brar, M.S., Kirjavainen, P.V., Chen, Y., Peng, J., Li, D. et al. (2016) High fat diet induced atherosclerosis is accompanied with low colonic bacterial diversity and altered abundances that correlates with plaque size, plasma A-FABP and cholesterol: a pilot study of high fat diet and its intervention with Lactobacillus rhamnosus GG (LGG) or telmisartan in ApoE(−/−) mice. BMC Microbiology, 16, 264. - PubMed
  16. Chauhan, N., Mittal, S., Tewari, S., Sen, J. & Laller, K. (2019) Association of apical periodontitis with cardiovascular disease via noninvasive assessment of endothelial function and subclinical atherosclerosis. Journal of Endodontics, 45, 681-690. - PubMed
  17. Chen, S., Lei, H., Luo, Y., Jiang, S., Zhang, M., Lv, H. et al. (2019) Micro-CT analysis of chronic apical periodontitis induced by several specific pathogens. International Endodontic Journal, 52, 1028-1039. - PubMed
  18. Conti, L.C., Segura-Egea, J.J., Cardoso, C.B.M., Benetti, F., Azuma, M.M., Oliveira, P.H.C. et al. (2020) Relationship between apical periodontitis and atherosclerosis in rats: lipid profile and histological study. International Endodontic Journal, 53, 1387-1397. - PubMed
  19. Daugherty, A. & Rateri, D.L. (2005) Development of experimental designs for atherosclerosis studies in mice. Methods, 36, 129-138. - PubMed
  20. Daugherty, A., Tall, A.R., Daemen, M., Falk, E., Fisher, E.A., García-Cardeña, G et al. (2017) Recommendation on design, execution, and reporting of animal atherosclerosis studies: a scientific statement from the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology, 37, e131-e157. - PubMed
  21. Getz, G.S. & Reardon, C.A. (2012) Animal models of atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology, 32, 1104-1115. - PubMed
  22. Getz, G.S. & Reardon, C.A. (2015) Use of mouse models in atherosclerosis research. Methods in Molecular Biology, 1339, 1-16. - PubMed
  23. Getz, G.S. & Reardon, C.A. (2016) Do the Apoe−/− and Ldlr−/− mice yield the same insight on atherogenesis? Arteriosclerosis, Thrombosis, and Vascular Biology, 36, 1734-1741. - PubMed
  24. Gibson, F.C., Hong, C., Chou, H.-H., Yumoto, H., Chen, J., Lien, E. et al. (2004) Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation, 109, 2801-2806. - PubMed
  25. Gistera, A. & Hansson, G.K. (2017) The immunology of atherosclerosis. Nature Reviews Nephrology, 13, 368-380. - PubMed
  26. Gobalakrishnan, S., Asirvatham, S.S. & Janarthanam, V. (2016) Effect of silybin on lipid profile in hypercholesterolaemic rats. Journal of Clinical and Diagnostic Research, 10, FF01-05. - PubMed
  27. González-Navarro, B., Segura-Egea, J.J., Estrugo-Devesa, A., Pintó-Sala, X., Jane-Salas, E., Jiménez-Sánchez, M.C. et al. (2020) Relationship between apical periodontitis and metabolic syndrome and cardiovascular events: a cross-sectional study. Journal of Clinical Medicine, 9,3205. - PubMed
  28. Ishibashi, S., Goldstein, J.L., Brown, M.S., Herz, J. & Burns, D.K. (1994) Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. Journal of Clinical Investigation, 93, 1885-1893. - PubMed
  29. Jimenez-Sanchez, M.C., Cabanillas-Balsera, D., Areal-Quecuty, V., Velasco-Ortega, E., Martin-Gonzalez, J. & Segura-Egea, J.J. (2020) Cardiovascular diseases and apical periodontitis: association not always implies causality. Medicina Oral Patologia Oral Y Cirugia Bucal, 25, e652-e659. - PubMed
  30. Kalatzis-Sousa, N.G., Spin-Neto, R., Wenzel, A., Tanomaru-Filho, M. & Faria, G. (2017) Use of micro-computed tomography for the assessment of periapical lesions in small rodents: a systematic review. International Endodontic Journal, 50, 352-366. - PubMed
  31. Koeth, R.A., Wang, Z., Levison, B.S., Buffa, J.A., Org, E., Sheehy, B.T. et al. (2013) Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine, 19, 576-585. - PubMed
  32. Koren, O., Spor, A., Felin, J., Fak, F., Stombaugh, J., Tremaroli, V. et al. (2011) Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proceedings of the National Academy of Sciences of the United States of America, 108(Suppl. 1), 4592-4598. - PubMed
  33. Kramer, C.D., Simas, A.M., He, X., Ingalls, R.R., Weinberg, E.O. & Genco, C.A. (2017) Distinct roles for dietary lipids and Porphyromonas gingivalis infection on atherosclerosis progression and the gut microbiota. Anaerobe, 45, 19-30. - PubMed
  34. López-López, J., Jané-Salas, E., Estrugo-Devesa, A., Castellanos-Cosano, L., Martín-González, J., Velasco-Ortega, E. et al. (2012) Frequency and distribution of root-filled teeth and apical periodontitis in an adult population of Barcelona, Spain. International Dental Journal, 62, 40-46. - PubMed
  35. Love, M.I., Huber, W. & Anders, S. (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15, 550. - PubMed
  36. Mandal, S., Van Treuren, W., White, R.A., Eggesbo, M., Knight, R. & Peddada, S.D. (2015) Analysis of composition of microbiomes: a novel method for studying microbial composition. Microbial Ecology in Health and Disease, 26, 27663. - PubMed
  37. Nagendrababu, V., Kishen, A., Murray, P.E., Nekoofar, M.H., Figueiredo, J.A.P., Priya, E. et al. (2021) PRIASE 2021 guidelines for reporting animal studies in Endodontology: a consensus-based development. International Endodontic Journal, 54, 848-857. - PubMed
  38. Nakashima, Y., Plump, A.S., Raines, E.W., Breslow, J.L. & Ross, R. (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arteriosclerosis Thrombosis, 14, 133-140. - PubMed
  39. Persoon, I.F. & Ozok, A.R. (2017) Definitions and epidemiology of endodontic infections. Current Oral Health Reports, 4, 278-285. - PubMed
  40. Petersen, J., Glaßl, E.-M., Nasseri, P., Crismani, A., Luger, A.K., Schoenherr, E. et al. (2014) The association of chronic apical periodontitis and endodontic therapy with atherosclerosis. Clinical Oral Investigations, 18, 1813-1823. - PubMed
  41. Rom, O., Korach-Rechtman, H., Hayek, T., Danin-Poleg, Y., Bar, H., Kashi, Y. et al. (2017) Acrolein increases macrophage atherogenicity in association with gut microbiota remodeling in atherosclerotic mice: protective role for the polyphenol-rich pomegranate juice. Archives of Toxicology, 91, 1709-1725. - PubMed
  42. Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W.S. et al. (2011) Metagenomic biomarker discovery and explanation. Genome Biology, 12, R60. - PubMed
  43. Segura-Egea, J.J., Martin-Gonzalez, J. & Castellanos-Cosano, L. (2015) Endodontic medicine: connections between apical periodontitis and systemic diseases. International Endodontic Journal, 48, 933-951. - PubMed
  44. Shapiro, M.D. & Fazio, S. (2016) From lipids to inflammation: new approaches to reducing atherosclerotic risk. Circulation Research, 118, 732-749. - PubMed
  45. Simas, A.M., Kramer, C.D., Weinberg, E.O. & Genco, C.A. (2021) Oral infection with a periodontal pathogen alters oral and gut microbiomes. Anaerobe, 71, 102399. - PubMed
  46. Suh, J.S., Kim, S., Bostrom, K.I., Wang, C.Y., Kim, R.H. & Park, N.H. (2019) Periodontitis-induced systemic inflammation exacerbates atherosclerosis partly via endothelial-mesenchymal transition in mice. International Journal of Oral Science, 11, 21. - PubMed
  47. Sullivan, M., Gallagher, G. & Noonan, V. (2016) The root of the problem: occurrence of typical and atypical periapical pathoses. Journal of the American Dental Association, 147, 646-649. - PubMed
  48. Tang, W.H.W., Wang, Z., Levison, B.S., Koeth, R.A., Britt, E.B., Fu, X. et al. (2013) Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine, 368, 1575-1584. - PubMed
  49. Tymchuk, C.N., Hartiala, J., Patel, P.I., Mehrabian, M. & Allayee, H. (2006) Nonconventional genetic risk factors for cardiovascular disease. Current Atherosclerosis Reports, 8, 184-192. - PubMed
  50. Vazquez-Baeza, Y., Pirrung, M., Gonzalez, A. & Knight, R. (2013) EMPeror: a tool for visualizing high-throughput microbial community data. Gigascience, 2, 16. - PubMed
  51. Wang, C.Y. & Stashenko, P. (1991) Kinetics of bone-resorbing activity in developing periapical lesions. Journal of Dental Research, 70, 1362-1366. - PubMed
  52. Wang, Z., Klipfell, E., Bennett, B.J., Koeth, R., Levison, B.S., DuGar, B. et al. (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472, 57-63. - PubMed
  53. Yu, V.S., Messer, H.H., Yee, R. & Shen, L. (2012) Incidence and impact of painful exacerbations in a cohort with post-treatment persistent endodontic lesions. Journal of Endodontics, 38, 41-46. - PubMed
  54. Zhang, J., Huang, X., Lu, B., Zhang, C. & Cai, Z. (2016) Can apical periodontitis affect serum levels of CRP, IL-2, and IL-6 as well as induce pathological changes in remote organs? Clinical Oral Investigations, 20, 1617-1624. - PubMed
  55. Zysset-Burri, D.C., Keller, I., Berger, L.E., Neyer, P.J., Steuer, C., Wolf, S. et al. (2019) Retinal artery occlusion is associated with compositional and functional shifts in the gut microbiome and altered trimethylamine-N-oxide levels. Scientific Reports, 9, 15303. - PubMed

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