Water-soluble dietary fiber alleviates cancer-induced muscle wasting through changes in gut microenvironment in mice.

Abstract

Cancer cachexia and the associated skeletal muscle wasting are considered poor prognostic factors, although effective treatment has not yet been established. Recent studies have indicated that the pathogenesis of skeletal muscle loss may involve dysbiosis of the gut microbiota and the accompanying chronic inflammation or altered metabolism. In this study, we evaluated the possible effects of modifying the gut microenvironment with partially hydrolyzed guar gum (PHGG), a soluble dietary fiber, on cancer-related muscle wasting and its mechanism using a colon-26 murine cachexia model. Compared with a fiber-free (FF) diet, PHGG contained fiber-rich (FR) diet-attenuated skeletal muscle loss in cachectic mice by suppressing the elevation of the major muscle-specific ubiquitin ligases Atrogin-1 and MuRF1, as well as the autophagy markers LC3 and Bnip3. Although tight-junction markers were partially reduced in both FR and FF diet-fed cachectic mice, the abundance of Bifidobacterium, Akkermansia, and unclassified S24-7 family increased by FR diet, contributing to the retention of the colonic mucus layer. The reinforcement of the gut barrier function resulted in the controlled entry of pathogens into the host system and reduced circulating levels of lipopolysaccharide-binding protein (LBP) and IL-6, which in turn led to the suppression of proteolysis by downregulating the ubiquitin-proteasome system and autophagy pathway. These results suggest that dietary fiber may have the potential to alleviate skeletal muscle loss in cancer cachexia, providing new insights for developing effective strategies in the future.

• Authors: Tomoki Sakakida, Takeshi Ishikawa, Toshifumi Doi, Ryuichi Morita, Yuki Endo, Shinya Matsumura, Takayuki Ota, Juichiro Yoshida, Yasuko Hirai, Katsura Mizushima, Yasuki Higashimura, Ken Inoue, Tetsuya Okayama, Kazuhiko Uchiyama, Tomohisa Takagi, Aya Abe, Ryo Inoue, Yoshito Itoh, Yuji Naito
• Journal: Cancer science (Cancer Sci) Vol. 113 Issue 5 Pg. 1789-1800 (May 2022) ISSN: 1349-7006 [Electronic] England
• PMID: 35201655 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Dietary Fiber
• Ubiquitin
• Water

Topics

• Animals
• Cachexia (etiology, prevention & control)
• Dietary Fiber (metabolism, pharmacology)
• Humans
• Mice
• Muscle, Skeletal
• Muscular Atrophy (pathology)
• Neoplasms (pathology)
• Tumor Microenvironment
• Ubiquitin (metabolism)
• Water (metabolism)