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Microbiome, Dec 02 2024, 12 (1) | https://doi.org/10.1186/s40168-024-01971-1
Host-specific effects of Eubacterium species on Rg3-mediated modulation of osteosarcopenia in a genetically diverse mouse population
Soyeon Hong1†, Bao Ngoc Nguyen2,3†, Huitae Min3, Hye-Young Youn3, Sowoon Choi3, Emmanuel Hitayezu4, Kwang-Hyun Cha4,5,6, Young Tae Park3,5, Choong-Gu Lee4,5,6, GyHye Yoo1,5* and Myungsuk Kim3,5,6*
1Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-Do 25451, Republic of Korea.
2College of Dentistry, Gangneung Wonju National University, Gangneung, Gangwon-Do, Republic of Korea.
3Center for Natural Product Efcacy Optimization, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, 679 Saimdang-Ro, Gangneung, Gangwon-Do 210-340, Republic of Korea.
4Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 25451, Republic of Korea.
5Department of Natural Product Applied Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
6Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-Do, Republic of Korea.
†Soyeon Hong and Bao Ngoc Nguyen contributed equally to this work.
*Correspondence: GyHye Yoo, Myungsuk Kim
1Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-Do 25451, Republic of Korea.
2College of Dentistry, Gangneung Wonju National University, Gangneung, Gangwon-Do, Republic of Korea.
3Center for Natural Product Efcacy Optimization, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, 679 Saimdang-Ro, Gangneung, Gangwon-Do 210-340, Republic of Korea.
4Center for Natural Product Systems Biology, Korea Institute of Science and Technology (KIST) Gangneung Institute, Gangneung 25451, Republic of Korea.
5Department of Natural Product Applied Science, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
6Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-Do, Republic of Korea.
†Soyeon Hong and Bao Ngoc Nguyen contributed equally to this work.
*Correspondence: GyHye Yoo, Myungsuk Kim
Abstract
Background: Osteosarcopenia, characterized by the simultaneous loss of bone and muscle mass, is a serious health problem in the aging population. This study investigated the interplay between host genetics, gut microbiota, and musculoskeletal health in a mouse model of osteosarcopenia, exploring the therapeutic potential of gut microbiota modulation.
Methods: We examined the effects of Rg3, a phytochemical, on osteosarcopenia and its interactions with host genetics and gut microbiota in six founder strains of the Collaborative Cross (CC) population. Subsequently, we evaluated the therapeutic potential of Eubacterium nodatum (EN) and Eubacterium ventriosum (EV), two gut microbes identified as significant correlates of Rg3-mediated osteosarcopenia improvement, in selected C57BL/6 J (B6) and 129S1/SvImJ (129S1) mouse strains.
Results: Rg3 treatment altered gut microbiota composition aligned with osteosarcopenia phenotypes, which response varied depending on host genetics. This finding enabled the identification of two microbes in the Eubacterium genus, potential mediator of Rg3 effect on osteosarcopenia. Oral administration of EN and EV differentially impacted bone density, muscle mass, exercise performance, and related gene expression in a mouse strain-specific manner. In 129S1 mice, EN and EV significantly improved these parameters, effectively reversing osteosarcopenic phenotypes. Mechanistic investigations revealed that these effects were mediated through the modulation of osteoblast differentiation and protein degradation pathways. In contrast, EN and EV did not significantly improve osteosarcopenic phenotypes in B6 mice, although they did modulate mitochondrial biogenesis and microbial diversity.
Conclusions: Our findings underscore the complex interplay between host genetics and the gut microbiota in osteosarcopenia and emphasize the need for personalized treatment strategies. EN and EV exhibit strain-specific therapeutic effects, suggesting that tailoring microbial interventions to individual genetic backgrounds may be crucial for optimizing treatment outcomes.
Methods: We examined the effects of Rg3, a phytochemical, on osteosarcopenia and its interactions with host genetics and gut microbiota in six founder strains of the Collaborative Cross (CC) population. Subsequently, we evaluated the therapeutic potential of Eubacterium nodatum (EN) and Eubacterium ventriosum (EV), two gut microbes identified as significant correlates of Rg3-mediated osteosarcopenia improvement, in selected C57BL/6 J (B6) and 129S1/SvImJ (129S1) mouse strains.
Results: Rg3 treatment altered gut microbiota composition aligned with osteosarcopenia phenotypes, which response varied depending on host genetics. This finding enabled the identification of two microbes in the Eubacterium genus, potential mediator of Rg3 effect on osteosarcopenia. Oral administration of EN and EV differentially impacted bone density, muscle mass, exercise performance, and related gene expression in a mouse strain-specific manner. In 129S1 mice, EN and EV significantly improved these parameters, effectively reversing osteosarcopenic phenotypes. Mechanistic investigations revealed that these effects were mediated through the modulation of osteoblast differentiation and protein degradation pathways. In contrast, EN and EV did not significantly improve osteosarcopenic phenotypes in B6 mice, although they did modulate mitochondrial biogenesis and microbial diversity.
Conclusions: Our findings underscore the complex interplay between host genetics and the gut microbiota in osteosarcopenia and emphasize the need for personalized treatment strategies. EN and EV exhibit strain-specific therapeutic effects, suggesting that tailoring microbial interventions to individual genetic backgrounds may be crucial for optimizing treatment outcomes.
논문정보
- Research article
- 2024년 12월 (BRIC 등록일 2024-12-03)
- 국내 연구진
- 생명과학 > 생명과학 기타
관련 웨비나
![유전적 다양성 마우스 모델에서 Rg3 매개 골근감소증 조절에 대한 유박테리움 종의 숙주 특이적 효과 [Microbiome]](/upload/board/files/onseminar/thumb/thumb_0000844.png)
학술웨비나
유전적 다양성 마우스 모델에서 Rg3 매개 골근감소증 조절에 대한 유박테리움 종의 숙주 특이적 효과 [Microbiome] 본 세미나에서는 노인성 근골격 감소증(osteosarcopenia)에 대한 최신 연구 결과를 소개하고, 숙주 유전학과 장내 미생물의 상호작용을 고려한 개인 맞춤형 치료 전략 개발의 필요성을 논의합니다. 본 연구에서는 유전적으로 다양한 Collaborative cross 창시자 계통 마우스 모델을 활용하여 Rg3(인삼 사포닌) 및 특정 유박테리움 종이 노인성 근골격 감소증에 미치는 영향을 분석했습니다. 그 결과, Rg3는 장내 미생물 구성 변화를 통해 골밀도, 근육량, 운동 능력을 개선하는 것으로 나타났으며, 그 효과는 숙주 유전형에 따라 다르게 나타났습니다. 또한, 특정 유박테리움 종은 숙주 유전형에 따라 골밀도, 근육량, 운동 능력 및 관련 유전자 발현에 차별적인 영향을 미치는 것으로 확인되었습니다. 본 연구 결과는 노인성 근골격 감소증 치료에 있어 숙주 유전형과 장내 미생물 간의 복잡한 상호 작용을 강조하며, 개인 맞춤형 치료 전략 개발의 필요성을 시사합니다.- 김명석(한국과학기술연구원(KIST))
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