口-肠轴：昼夜节律紊乱影响牙周炎的潜在机制 

李澍 张晔 

暨南大学口腔医学院，广东省广州市，510000； 

摘要：人体内有数万亿个微生物定植，尤其是口腔和肠道是人体内微生物定植最丰富的区域。口腔、肠道微生物 已被证实可以转移并相互影响，口腔-肠道微生物轴的稳态影响着口腔、肠道乃至全身健康。哺乳动物、微生物、 病原体等大多数生物都受环境昼夜节律的调节，因此人体的昼夜节律紊乱会改变口腔及肠道菌群稳态进而破坏此 轴的稳定性，导致口腔和肠道中的有害菌增殖，而这些有害菌与牙周炎的发生密切相关。 

关键词：昼夜节律紊乱；微生物群；口腔-肠道轴；牙周炎；免疫系统 

参考文献

[1]Xian, Peng, et al. "The oral microbiome bank of China." International journal of oral science10.2 (2018): 16.

[2]Morris, Christopher J., Jessica N. Yang, and Frank AJL Scheer. "The impact of the circadian timing system on cardiovascular and metabolic function." Progress in brain research 199 (2012): 337-358.

[3]Gilbert, Jack A., et al. "Current understanding of the human microbiome." Nature medicine 24.4 (2018): 392-400.

[4]Schmidt, Thomas SB, et al. "Extensive transmission of microbes along the gastrointestinal tract." elife 8 (2019): e42693.

[5]Xue, Ying, et al. "Indoleamine 2, 3-dioxygenase expression regulates the survival and proliferation of Fusobacterium nucleatum in THP-1-derived macrophages." Cell death & disease 9.3 (2018): 355.

[6]Schmidt TSB，Hayward MR，Coelho LP，Li SS，Costea PI (2018) European Nucleotide Archive ID PRJEB28422. The Salivary Microbiome in Health and Disease.

[7]Hajishengallis, George, and Richard J. Lamont. "Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology." Molecular oral microbiology 27.6 (2012): 409-419.

[8]Socransky, Sigmund S., and Anne D. Haffajee. "Dental biofilms: difficult therapeutic targets." Periodontology 2000 28.1 (2002): 12-55.

[9]Kitamoto, Sho, et al. "The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis." Cell 182.2 (2020): 447-462.

[10]Nagao, Jun-ichi, et al. "Pathobiont-responsive Th17 cells in gut-mouth axis provoke inflammatory oral disease and are modulated by intestinal microbiome." Cell Reports 40.10 (2022).

[11]Wang, Qiqi, et al. "Gut microbiota-dependent trimethylamine n-oxide pathway contributes to the bidirectional relationship between intestinal inflammation and periodontitis." Frontiers in Cellular and Infection Microbiology 12 (2023): 1125463.

[12]Brown, Gregory M. "Light, melatonin and the sleep-wake cycle." Journal of Psychiatry and Neuroscience.19.5 (1994): 345.

[13]Reid, Kathryn J., and Sabra M. Abbott. "Jet lag and shift work disorder." Sleep medicine clinics 10.4 (2015): 523-535.

[14]Brooks, John F., and Lora V. Hooper. "Interactions among microbes, the immune system, and the circadian clock." Seminars in Immunopathology. Vol. 42. No. 6. Berlin/Heidelberg: Springer Berlin Heidelberg, 2020.

[15]Grobbelaar, N., et al. "Dinitrogen-fixing endogenous rhythm in Synechococcus RF-1." FEMS Microbiology Letters 37.2 (1986): 173-177.

[16]Chellappa, Sarah L., et al. "Proof-of-principle demonstration of endogenous circadian system and circadian misalignment effects on human oral microbiota." FASEB journal: official publication of the Federation of American Societies for Experimental Biology 36.1 (2022): e22043.

[17]Thaiss, Christoph A., et al. "Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis." Cell 159.3 (2014): 514-529.

[18]Liang, Xue, Frederic D. Bushman, and Garret A. FitzGerald. "Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock." Proceedings of the National Academy of Sciences 112.33 (2015): 10479-10484.

[19]Liu, Xiaomeng, et al. "Circadian rhythm disorders aggravate periodontitis by modulating BMAL1."International journal of molecular sciences 24.1 (2022): 374.

[20]Ma, Xueying, et al. "Circadian rhythm disruption exacerbates the progression of macrophage dysfunction and alveolar bone loss in periodontitis." International Immunopharmacology 116 (2023): 109796.

[21]Balaji, Thodur Madapusi, et al. "Melatonin levels in periodontitis vs. the healthy state: A systematic review and meta‐analysis." Oral Diseases 28.2 (2022): 284-306.

[22]Anton DM, Martu MA, Maris M, Maftei GA, Sufaru IG, Tatarciuc D, Luchian I, Ioanid N, Martu S. Study on the Effects of Melatonin on Glycemic Control and Periodontal Parameters in Patients with Type II Diabetes Mellitus and Periodontal Disease. Medicina (Kaunas). 2021 Feb 5;57(2):140. doi: 10.3390/medicina57020140.