Gut dysbiosis from high-salt diet promotes glioma via propionate-mediated TGF-β activation.

in The Journal of experimental medicine by 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

TLDR

  • The study finds that a high-salt diet induces alterations in gut microbiota, leading to elevated levels of propionate, which accelerates glioma growth and invasion.
  • The findings suggest a connection between gut microbiota and glioma progression, and identify TGF-β signaling and hypoxic response as potential therapeutic targets.

Abstract

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.

Overview

  • The study investigates the impact of a high-salt diet (HSD) on the progression of glioma, a type of brain cancer, commonly found in Western countries.
  • The researchers found that alterations in gut microbiota caused by an HSD facilitated the development of glioma.
  • The primary objective of the study is to establish a connection between gut microbiota and the progression of glioma.

Comparative Analysis & Findings

  • Mice fed an HSD had elevated levels of intestinal propionate, which accelerated the growth of glioma cells.
  • Propionate supplementation enhanced the response of glioma cells to low oxygen levels, and increased the expression of HIF-1α, leading to an increase in TGF-β1 production.
  • Propionate treatment promoted glioma cell invasion through TGF-β signaling, and a link was identified between TGF-β signaling, response to low oxygen levels, and invasion-related pathways.

Implications and Future Directions

  • The study's 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.
  • Future research directions include exploring novel therapeutic targets for glioma treatment, such as modulating the gut microbiota to prevent or slow down glioma progression.
  • It is also essential to investigate the role of HSD in other types of cancer and to identify potential biomarkers for early detection and diagnosis of glioma.
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