Elucidation of novel mechanisms by which intestinal bacteria affect bone-glycolytic metabolism-immune network

• Project/Area Number: 18K17282
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57080:Social dentistry-related
• Research Institution: Okayama University
• Principal Investigator: Fukuhara Yoko 岡山大学, 医歯薬学総合研究科, 助教 (60779742)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腸内細菌叢 / 無菌マウス / 軟骨細胞 / 内軟骨性骨形成 / 母体腸内細菌 / 胎児骨格発達 / 骨代謝 / 細菌細胞外小胞 / 実験的歯周炎 / 臼歯結紮 / 腸内細菌 / マイクロCT / RNA-seq / 骨芽細胞 / オステオカルシン / IGF-1 / 常在菌 / 内軟骨性骨成長

Outline of Final Research Achievements

Recently, there is accumulating evidence that bone is an organ that not only supports the whole body but also plays an important role in maintaining health in association with intestinal bacteria and immune function. In this study, we analyzed the mechanism that controls bone metabolism and endochondral bone formation by intestinal bacteria using germ-free (GF) and bacterial-carrying "specific pathogen free (SPF)" mice. From the skeletal analysis of GF and SPF mice and the analysis of calvaria-derived osteoblasts, gut microbiome activates both osteoclasts and osteoblasts and activate bone metabolism. Analysis of chondrocytes isolated from fetal costal cartilage suggests that the presence of maternal microbiome may negatively regulate endochondral bone formation during embryonic period.

Academic Significance and Societal Importance of the Research Achievements

我々の仮説は母体腸内細菌叢が胎生期から胎児骨格制御を行うというものであり、その分子メカニズムを解明することは歯科のみならず産科・小児科学的にも重要な意義をもつ。
腸内細菌叢は臓器のひとつであり、これらにより我々の健康が制御されているといっても過言ではない。近年、腸内細菌叢の影響は一個人だけでなく、母親―胎児間といった垂直的な影響も注目され始めているが、垂直的な腸内細菌叢と骨との関係についての報告は、ほぼ皆無である。本研究により胎児の骨格成長発育に影響を与える分子機構を明らかにすることで、妊娠前の状態がいかに胎児に影響を与えるか新しい知見をを広く社会に広めることができ、国民の健康増進に寄与できる。

Research Products

• [Journal Article] Caries Increment and Salivary Microbiome during University Life: A Prospective Cohort Study. (2020)
  • Author(s): Uchida-Fukuhara Y, Ekuni D, Islam MM, Kataoka K, Taniguchi-Tabata A, Fukuhara D, Toyama N, Kobayashi T, Fujimori K, Sawada N, Iwasaki Y, Morita M.
  • Journal Title: Int J Environ Res Public Health Volume: 17 Issue: 10 Pages: 3713-3713
  • DOI: 10.3390/ijerph17103713
  • Peer Reviewed / Open Access
• [Journal Article] Association between Sleep Quality and Duration and Periodontal Disease among University Students: A Cross-Sectional Study (2020)
  • Author(s): Islam MM, Ekuni D, Toyama N, Taniguchi-Tabata A, Kataoka K, Uchida-Fukuhara Y, Fukuhara D, Saho H, Sawada N, Nakashima Y, Iwasaki Y, Morita M.
  • Journal Title: Int J Environ Res Public Health Volume: 17 Issue: 9 Pages: 3034-3034
  • DOI: 10.3390/ijerph17093034
  • Peer Reviewed / Open Access
• [Journal Article] Association between Household Exposure to Secondhand Smoke and Dental Caries among Japanese Young Adults: A Cross-Sectional Study. (2020)
  • Author(s): Saho H, Taniguchi-Tabata A, Ekuni D, Yokoi A, Kataoka K, Fukuhara D, Toyama N, Islam MM, Sawada N, Nakashima Y, Nakahara M, Deguchi J, Uchida-Fukuhara Y, Yoneda T, Iwasaki Y, Morita M.
  • Journal Title: Int J Environ Res Public Health Volume: 17 Issue: 22 Pages: 8623-8623
  • DOI: 10.3390/ijerph17228623
  • Peer Reviewed / Open Access
• [Journal Article] Outer membrane vesicles derived from porphylomonas gingivalis induced cell death with disruption of tight junctions in human lung epithelial cells. (2020)
  • Author(s): He Y, Shiotsu N, Uchida-Fukuhara Y, Guo J, Weng Y, Ikegame M, Wang Z, Ono K, Kamioka H, Torii Y, Sasaki A, Yoshida K, Okamura H.
  • Journal Title: Archives of Oral Biolog Volume: 118 Pages: 104841-104841
  • DOI: 10.1016/j.archoralbio.2020.104841
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Relationship between oral hygiene knowledge, source of oral hygiene knowledge and oral hygiene behavior in Japanese university students: A prospective cohort study. (2020)
  • Author(s): Fukuhara D, Ekuni D, Kataoka K, Taniguchi-Tabata A, Uchida-Fukuhara Y, Toyama N, Yoneda T, Sugiura Y, Islam MM, Saho H, Iwasaki Y, Morita M.
  • Journal Title: PLoS One. Volume: 15 Issue: 7 Pages: e0236259-e0236259
  • DOI: 10.1371/journal.pone.0236259
  • Peer Reviewed / Open Access
• [Journal Article] Association between maternal periodontal status and ultrasonographic measurement of fetal growth: A longitudinal study. (2020)
  • Author(s): Taniguchi-Tabata A, Takeuchi N, Uchida Y, Ekuni D, Morita M.
  • Journal Title: Sci Rep Volume: 10 Issue: 1 Pages: 1402-1402
  • DOI: 10.1038/s41598-020-58396-7
  • Peer Reviewed / Open Access
• [Journal Article] Associations between sleep bruxism, sleep quality, and exposure to secondhand smoke in Japanese young adults: a cross-sectional study. (2020)
  • Author(s): Toyama N, Ekuni D, Taniguchi-Tabata A, Yoneda T, Kataoka K, Yokoi A, Uchida Y, Fukuhara D, Saho H, Monirul IM, Sawada N, Nakashima Y, Iwasaki Y, Morita M.
  • Journal Title: Sleep Med Volume: 68 Pages: 57-62
  • DOI: 10.1016/j.sleep.2019.09.003
  • Peer Reviewed
• [Journal Article] Relationship of Salivary Microbiome with the Worsening of the Periodontal Health Status in Young Adults: A 3-Year Cohort Study. (2020)
  • Author(s): Islam MM, Ekuni D, Toyama N, Kobayashi T, Fujimori K, Uchida Y, Fukuhara D, Taniguchi-Tabata A, Kataoka K, Iwasaki Y, Morita M.
  • Journal Title: Int J Environ Res Public Health Volume: 17 Issue: 5 Pages: 1764-1764
  • DOI: 10.3390/ijerph17051764
  • NAID: 120006847417
  • Peer Reviewed / Open Access
• [Journal Article] Circadian production of melatonin in cartilage modifies rhythmic gene expression (2019)
  • Author(s): Fu Shanqi、Kuwahara Miho、Uchida Yoko、Kondo Sei、Hayashi Daichi、Shimomura Yuji、Takagaki Asami、Nishida Takashi、Maruyama Yusuke、Ikegame Mika、Hattori Atsuhiko、Kubota Satoshi、Hattori Takako
  • Journal Title: Journal of Endocrinology Volume: 241 Issue: 2 Pages: 161-173
  • DOI: 10.1530/joe-19-0022
  • NAID: 120006801909
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities (2018)
  • Author(s): Uchida Yoko、Irie Koichiro、Fukuhara Daiki、Kataoka Kota、Hattori Takako、Ono Mitsuaki、Ekuni Daisuke、Kubota Satoshi、Morita Manabu
  • Journal Title: Molecules Volume: 23 Issue: 7 Pages: 1517-1517
  • DOI: 10.3390/molecules23071517
  • Peer Reviewed / Open Access
• [Presentation] Effects of maternal gut microbiome on fetal endochondral bone formation (2020)
  • Author(s): Uchida-Fukuhara，Y., Hattori, T., Ikegame, M., Kubota,S., Okamura, H.
  • Organizer: 第62回歯科基礎医学会
• [Presentation] 腸内細菌の有無が胎児内軟骨成長に与える影響 (2020)
  • Author(s): 内田瑶子、服部高子、福原大樹、Fu Shanqi、近藤 星、桑原実穂、イスラム モニルル、片岡広太、江國大輔、久保田聡、森田 学
  • Organizer: 第33回日本軟骨代謝学会
• [Presentation] Effect of melatonin on rhythmic gene expression in human articular chondrocytes. (2020)
  • Author(s): Fu, S., Kuwahara, M., Uchida, Y., Hyashi, D., Shimomura, Y., Takagaki, A., Nishida, T., Nakata, E., Furumatsu, T., Kondo, S., Maruyama, Y., Hattori, A., Kubota, S., Hattori, T
  • Organizer: 第93回日本生化学会大会
• [Presentation] Effect of melatonin on rhythmic gene expression in human articular cartilage. (2020)
  • Author(s): Fu, S., Kuwahara, M., Uchida, Y., Kondo, S., Hyashi, D., Shimomura, Y., Takagaki, A., Nishida, T., Maruyama, Y., Ikegami, M., Hattori, A., Kubota, S., Hattori
  • Organizer: 第38回日本骨代謝学会学術集会
• [Presentation] 腸内細菌が胎生期内軟骨性骨形成に与える影響 (2020)
  • Author(s): 内田瑶子，服部高子，フー・シャンキー，近藤 星，桑原実穂，福原大樹 ，モハマドモニルルイスラム，片岡広太 ，江國大輔 ，久保田 聡 ，森田 学
  • Organizer: 岡山大学次世代研究拠点シンポジウム2020
• [Presentation] The impact of gut microbiome on embryonic endochondral ossification (2020)
  • Author(s): Yoko Uchida，Takako Hattori，Fu Shanqi，Sei Kondo，Miho Kuwahara，Daiki Fukuhara，Kota Kakaoka，Daisuke Ekuni，Satoshi Kubota，Manabu Morita
  • Organizer: 第33回日本軟骨代謝学会（新型コロナウイルスの影響にて延期）
• [Presentation] Commensal microbiota enhanced both osteoclast and osteoblast activities. (2018)
  • Author(s): Yoko Uchida, Koichiro Irie, Daiki Fukuhara, Kota Kataoka, Takako Hattori, Mitsuaki Ono, Daisuke Ekuni, Satoshi Kubota, and Manabu Morita
  • Organizer: ASEAN-JAPAN Genome Medicine Research Promotion Conference
  • Int'l Joint Research
• [Presentation] Circadian production of melatonin and its receptors in cartilage influences chondrocyte rhythmic gene expression (2018)
  • Author(s): Fu Shanqi,Miho Kuwahara,Yoko Uchida,Daichi Hayashi,Yuji Shimomura,Asami Takagaki,Takashi Nishida,Yusuke Maruyama,Mika Ikegame,Atsuhiko Hattori,Takako Hattori,Satoshi Kubota
  • Organizer: 第91回日本生化学会大会