The purpose of this study is to investigate the impact of a high-salt diet (HSD), which is commonly found in Western countries, on the progression of glioma. Our research shows that the alterations in gut microbiota caused by an HSD facilitated the development of glioma. Mice fed an HSD have elevated levels of intestinal propionate, which accelerated the growth of glioma cells. We also find that propionate supplementation enhanced the response of glioma cells to low oxygen levels. Moreover, we identify a link between TGF-β signaling, response to low oxygen levels, and invasion-related pathways. Propionate treatment increases the expression of HIF-1α, leading to an increase in TGF-β1 production. Additionally, propionate treatment promotes glioma cell invasion through TGF-β signaling. Our findings suggest that an HSD-induced increase in propionate plays a crucial role in glioma progression by facilitating invasion through the hypoxic response and TGF-β signaling pathways, thereby establishing a significant connection between gut microbiota and the progression of glioma.
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May 22 2025
Gut dysbiosis from high-salt diet promotes glioma via propionate-mediated TGF-β activation
Chae Won Kim
,
Chae Won Kim
*
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
2
KAIST Life Science Institute, KAIST
, Daejeon, Republic of Korea
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Hyun-Jin Kim
,
Hyun-Jin Kim
*
(Conceptualization, Investigation, Writing - original draft)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
2
KAIST Life Science Institute, KAIST
, Daejeon, Republic of Korea
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In Kang
,
In Kang
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Keun Bon Ku
,
Keun Bon Ku
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
4Department of Convergent Research of Emerging Virus Infection,
Korea Research Institute of Chemical Technology
, Daejeon, Republic of Korea
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Yumin Kim
,
Yumin Kim
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
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Jang Hyun Park
,
Jang Hyun Park
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
2
KAIST Life Science Institute, KAIST
, Daejeon, Republic of Korea
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Juhee Lim
,
Juhee Lim
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Byeong Hoon Kang
,
Byeong Hoon Kang
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Won Hyung Park
,
Won Hyung Park
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Jeongwoo La
,
Jeongwoo La
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Sungwoo Chang
,
Sungwoo Chang
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
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Inju Hwang
,
Inju Hwang
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Minji Kim
,
Minji Kim
(Investigation)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
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Stephen Ahn
,
Stephen Ahn
(Methodology, Resources)
5Department of Neurosurgery,
Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
, Seoul, Republic of Korea
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Heung Kyu Lee
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
Correspondence to Heung Kyu Lee: [email protected]
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Chae Won Kim
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Validation, Visualization, Writing - original draft, Writing - review & editing
*
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
2
KAIST Life Science Institute, KAIST
, Daejeon, Republic of Korea
Hyun-Jin Kim
Conceptualization, Investigation, Writing - original draft
*
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
2
KAIST Life Science Institute, KAIST
, Daejeon, Republic of Korea
In Kang
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Keun Bon Ku
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
4Department of Convergent Research of Emerging Virus Infection,
Korea Research Institute of Chemical Technology
, Daejeon, Republic of Korea
Yumin Kim
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
Jang Hyun Park
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
2
KAIST Life Science Institute, KAIST
, Daejeon, Republic of Korea
Juhee Lim
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Byeong Hoon Kang
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Won Hyung Park
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Jeongwoo La
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Sungwoo Chang
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
Inju Hwang
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Minji Kim
Investigation
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
3
Graduate School of Medical Science and Engineering, KAIST
, Daejeon, Republic of Korea
Stephen Ahn
Methodology, Resources
5Department of Neurosurgery,
Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea
, Seoul, Republic of Korea
Heung Kyu Lee
Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1Laboratory of Host Defenses, Department of Biological Sciences,
Korea Advanced Institute of Science and Technology (KAIST)
, Daejeon, Republic of Korea
Correspondence to Heung Kyu Lee: [email protected]
*
C.W. Kim and H.-J. Kim contributed equally to this paper.
Disclosures: The authors declare no competing interests exist.
Received:
July 02 2024
Revision Received:
March 08 2025
Accepted:
May 05 2025
Online ISSN: 1540-9538
Print ISSN: 0022-1007
Funding
Funder(s):
National Research Foundation of Korea
- Award Id(s): RS-2022-NR071193,RS-2021-NR056438,RS-2023-NR077244,RS-2024-00439735
© 2025 Kim et al.
2025
Kim et al.
This article is distributed under the terms as described at https://rupress.org/pages/terms102024/.
J Exp Med (2025) 222 (8): e20241135.
Article history
Received:
July 02 2024
Revision Received:
March 08 2025
Accepted:
May 05 2025
Citation
Chae Won Kim, Hyun-Jin Kim, In Kang, Keun Bon Ku, Yumin Kim, Jang Hyun Park, Juhee Lim, Byeong Hoon Kang, Won Hyung Park, Jeongwoo La, Sungwoo Chang, Inju Hwang, Minji Kim, Stephen Ahn, Heung Kyu Lee; Gut dysbiosis from high-salt diet promotes glioma via propionate-mediated TGF-β activation. J Exp Med 4 August 2025; 222 (8): e20241135. doi: https://doi.org/10.1084/jem.20241135
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