Research progress on oral homeostasis imbalance in microgravity environment

doi:10.3969/j.issn.1006-7795.2025.06.010

Abstract

Abstract: With the rapid development of manned spaceflight technology, the impact of microgravity environment on the oral homeostasis of astronauts in space missions has attracted increasing attention. This article reviewed the latest research progress of microgravity on oral homeostasis imbalance, focusing on the effects of microgravity on maxillofacial soft and hard tissues (alveolar bone, periodontal tissues, salivary glands and masticatory muscles), oral microbiome, and maxillofacial stem cells. Microgravity can lead to alveolar bone resorption, aggravation of periodontitis, alterations in saliva composition and microbiome imbalance, which in turn increases the risk of oral diseases such as caries and periodontitis, but it can promote the proliferation and differentiation of maxillofacial stem cells. Further, this review outlines prospective research directions of the oral health protection of astronauts.

Key words: microgravity, weightlessness, oral homeostasis, oral microbiome, maxillofacial stem cells, bone metabolism

CLC Number:

Zhang Qi, Wang Xueling, Zhou Jian. Research progress on oral homeostasis imbalance in microgravity environment[J]. Journal of Capital Medical University, 2025, 46(6): 1026-1032.

References

［1］Rogers M J B, Vogt G L, Wargo M J. Microgravity: a teacher’s guide with activities in science, mathematics, and technology EG-1997-08-110-HQ［R］. Washington: National Aeronautics and Space Administration, 1997.
［2］Qaisar R. From aging to space: a comparative biology of skeletal muscle degeneration［J］. Biochim Biophys Acta Mol Basis Dis, 2025, 1872(1): 168058.
［3］Mircea A A, Pistritu D V, Fortner A, et al. Space travel: the radiation and microgravity effects on the cardiovascular system［J］. Int J Mol Sci, 2024, 25(21): 11812.
［4］周建，潘雯，李晓钰，等. 经口腔唾液腺转运的硝酸盐循环对全身健康的重要作用［J］. 科学通报, 2023, 68(34): 4726－4736.
［5］Zhou J, Liu H, Hu L, et al. Nitrate and body homeostasis［J］. Med Plus, 2024, 1(1): 23－44.
［6］Del F M, Khijmatgar S, Vandenberghe B, et al. Oral health of astronauts in short- and long-term missions in space［J］. Aerosp Med Hum Perform, 2025, 96(2): 168－179.
［7］Sonawane R, Patil S, Rahaman J, et al. Effect of microgravity on bone tissue: mechanisms of osteodegeneration and advanced treatment modalities［J］. Biochem Biophys Res Commun, 2025, 771: 152055.
［8］Ghosh P, Stabley J N, Behnke B J, et al. Effects of spaceflight on the murine mandible: possible factors mediating skeletal changes in non-weight bearing bones of the head［J］. Bone, 2016, 83: 156－161.
［9］Dagdeviren D, Kalajzic Z, Adams D J, et al. Responses to spaceflight of mouse mandibular bone and teeth［J］. Arch Oral Biol, 2018, 93: 163－176.
［10］Rai B, Kaur J, Catalina M. Bone mineral density, bone mineral content, gingival crevicular fluid (matrix metalloproteinases, cathepsin K, osteocalcin), and salivary and serum osteocalcin levels in human mandible and alveolar bone under conditions of simulated microgravity［J］. J Oral Sci, 2010, 52(3): 385－390.
［11］Coulombe J C, Senwar B, Ferguson V L. Spaceflight-induced bone tissue changes that affect bone quality and increase fracture risk［J］. Curr Osteoporos Rep, 2020, 18(1) : 1－12.
［12］Genah S, Monici M, Morbidelli L. The effect of space travel on bone metabolism: considerations on todays major challenges and advances in pharmacology［J］. Int J Mol Sci, 2021, 22(9): 4585.
［13］Rai B, Kaur J, Catalina M, et al. Effect of simulated microgravity on salivary and serum oxidants, antioxidants, and periodontal status［J］. J Periodontol, 2011, 82(10): 1478－1482.
［14］Bakri A, Ismail A, Mansour A, et al. Microgravity exacerbates periodontitis in vivo［J］. J Periodontal Res, 2025, 60(9): 940－942.
［15］Dagdeviren D, Beallias J, Khan I, et al. Response of the mouse sublingual gland to spaceflight［J］. Eur J Oral Sci, 2018, 126(5): 373－381.
［16］Hand A R, Dagdeviren D, Larson N A, et al. Effects of spaceflight on the mouse submandibular gland［J］. Arch Oral Biol, 2020, 110: 104621.
［17］Mednieks M, Khatri A, Hand A R. Salivary gland protein expression after Bion-M1 and space shuttle STS-135 missions［J］. Gravit Space Res, 2015, 3(1): 2－19.
［18］Ouchi T, Kono K, Satou R, et al. Upregulation of Amy1 in the salivary glands of mice exposed to a lunar gravity environment using the multiple artificial gravity research system［J］. Front Physiol, 2024, 15: 1417719.
［19］Sun H, Zhou Q, Qiao P, et al. Short-term head-down bed rest microgravity simulation alters salivary microbiome in young healthy men［J］. Front Microbiol, 2022, 13: 1056637.
［20］Agha N H, Baker F L, Kunz H E, et al. Salivary antimicrobial proteins and stress biomarkers are elevated during a 6-month mission to the international space station［J］. J Appl Physiol (1985), 2020, 128(2): 264－275.
［21］Krieger S S, Zwart S R, Mehta S, et al. Alterations in saliva and plasma cytokine concentrations during long-duration spaceflight［J］. Front Immunol, 2021, 12: 725748.
［22］Goyal A, Malhotra P, Bansal P, et al. Mission mars: a dentist’s perspective［J］. Br Interplanet Soc, 2015, 68: 393－399.
［23］Urbaniak C, Lorenzi H, Thissen J, et al. The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation［J］. Microbiome, 2020, 8(1): 56.
［24］Ghasemi S, Dashti M, Akbarboojar F M. Salivary stress biomarkers in flight crew during space missions to assess stress levels: a systematic review［J］. Int J Microgravity Sci, 2021, 38(3): 380305.
［25］Parafati M, Giza S, Shenoy T S, et al. Human skeletal muscle tissue chip autonomous payload reveals changes in fiber type and metabolic gene expression due to spaceflight［J］. NPJ Microgravity, 2023, 9(1): 77.
［26］张凯，牛忠英，王睿，等. 模拟失重对大鼠咬肌超微结构的影响［J］. 口腔颌面修复学杂志, 2013, 14(2): 74－77.
［27］Philippou A, Minozzo F C, Spinazzola J M, et al. Masticatory muscles of mouse do not undergo atrophy in space［J］. FASEB J, 2015, 29(7): 2769－2779.
［28］Salavatifar M, Ahmadi S M, Todorov S D, et al. Impact of microgravity on virulence, antibiotic resistance and gene expression in beneficial and pathogenic microorganisms［J］. Mini Rev Med Chem, 2023, 23(16): 1608－1622.
［29］Brown L R, Frome W J, Handler S, et al. Skylab oral health studies in biomedical results from skylab national aeronautics and space administration: NASA-SP-377［J］. Houston: Johnson Space Center, 1977.
［30］Morrison M D, Thissen J B, Karouia F, et al. Investigation of spaceflight induced changes to astronaut microbiomes［J］. Front Microbiol, 2021, 12: 659179.
［31］Zhu D, Qiao P, Zhou Q, et al. Effect of 15 days －6 degrees head-down bed rest on microbial communities of supragingival plaque in young men［J］. Front Microbiol, 2024, 15: 1331023.
［32］Satoh K, Yamazaki T, Furukawa S, et al. Identification of fungi isolated from astronaut nasal and pharyngeal smears and saliva［J］. Microbiol Immunol, 2021, 65(2): 89－94.
［33］Cheng X, Xu X, Chen J, et al. Effects of simulated microgravity on Streptococcus mutans physiology and biofilm structure［J］. FEMS Microbiol Lett, 2014, 359(1): 94－101.
［34］Orsini S S, Lewis A M, Rice K C. Investigation of simulated microgravity effects on Streptococcus mutans physiology and global gene expression［J］. NPJ Microgravity, 2017, 3: 4.
［35］Fernander M C, Parsons P K, Khaled B, et al. Adaptation to simulated microgravity in Streptococcus mutans［J］. NPJ Microgravity, 2022, 8(1): 17.
［36］Li Y, Liu Z, Luo G, et al. Effects of 60 days of 6 degrees head-down bed rest on the composition and function of the human gut microbiota［J］. iScience, 2023, 26(5): 106615.
［37］Ramos-Nascimento A, Grenga L, Haange S B, et al. Human gut microbiome and metabolite dynamics under simulated microgravity［J］. Gut Microbes, 2023, 15(2): 2259033.
［38］Wang M, Chen S, Zhong C, et al. The influence of simulated weightlessness on the composition and function of gut microbiota and bile acid metabolism products［J］. Life Sci Space Res (Amst), 2024, 41: 18－28.
［39］马兆峰，李石，牛忠英. 模拟微重力培养环境下牙周膜干细胞生长状态的研究［J］. 广东牙病防治, 2011, 9(19): 451－454.
［40］Li Y, He L, Pan S, et al. Three-dimensional simulated microgravity culture improves the proliferation and odontogenic differentiation of dental pulp stem cell in PLGA scaffolds implanted in mice［J］. Mol Med Rep, 2017, 15(2): 873－878.
［41］Hou H, Qiu Z, Che J, et al. Effects of simulated microgravity on dental pulp stem cell stemness［J］. J Mol Histol, 2025, 56(2): 97.［42］Li S, Ma Z, Niu Z, et al. NASA-approved rotary bioreactor enhances proliferation and osteogenesis of human periodontal ligament stem cells［J］. Stem Cells Dev, 2009, 18(9): 1273－1282.
［43］李彦，李石，牛忠英，等. 微重力环境下Smads信号通路对人牙周膜干细胞成骨向分化的影响［J］. 上海口腔医学, 2012, 21(3): 246－250.
［44］Kang B K, Zhu Z, Wang J, et al. Maintenance of adult stem cells from human minor salivary glands via the Wnt signaling pathway［J］. Stem Cell Res Ther, 2023, 14(1): 20.
［45］Kim J M, Minh T H, Jeon E J, et al. Effect of short-term gravitational changes on the human minor salivary gland stem cell characteristics［J］. J Oral Biosci, 2025, 67(1): 100625.
［46］He L, Pan S, Li Y, et al. Increased proliferation and adhesion properties of human dental pulp stem cells in PLGA scaffolds via simulated microgravity［J］. Int Endod J, 2016, 49(2): 161－173.
［47］Imura T, Otsuka T, Kawahara Y, et al. “Microgravity” as a unique and useful stem cell culture environment for cell-based therapy［J］. Regen Ther, 2019, 12: 2－5.
［48］Zhang W, Zhang J, Cui Y, et al. Stem cells and exosome applications for cutaneous wound fealing: from ground to microgravity environment［J］. Stem Cell Rev Rep, 2023, 19(7): 2094－2108.
［49］Topal U, Zamur C. Microgravity, stem cells, and cancer: a new hope for cancer treatment［J］. Stem Cells Int, 2021, 2021: 5566872.
［50］Xu Y, Sa Y, Zhang C, et al. A preventative role of nitrate for hypoxia-induced intestinal injury［J］. Free Radic Biol Med, 2024, 213: 457－469.
［51］Si Y, Du H, Li S, et al. Nitrate-driven maintenance of lipid homeostasis by M2 macrophages alleviates atherosclerosis via downregulation of LOX1 expression and reduction of lipid deposition［J］. Sci China Life Sci, 2025, 68(10): 2995－3009.

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