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Title: Metronidazole causes skeletal muscle atrophy and modulates muscle chronometabolism
Authors: Manickam, Ravikumar
Oh, Hui Yun Penny
Tan, Chek Kun
Paramalingam, Eeswari
Wahli, Walter
Keywords: Metronidazole
Gut Dysbiosis
Issue Date: 2018
Source: Manickam, R., Oh, H. Y. P., Tan, C. K., Paramalingam, E., & Wahli, W. (2018). Metronidazole causes skeletal muscle atrophy and modulates muscle chronometabolism. International Journal of Molecular Sciences, 19(8), 2418-. doi:10.3390/ijms19082418
Series/Report no.: International Journal of Molecular Sciences
Abstract: Antibiotics lead to increased susceptibility to colonization by pathogenic organisms, with different effects on the host-microbiota relationship. Here, we show that metronidazole treatment of specific pathogen-free (SPF) mice results in a significant increase of the bacterial phylum Proteobacteria in fecal pellets. Furthermore, metronidazole in SPF mice decreases hind limb muscle weight and results in smaller fibers in the tibialis anterior muscle. In the gastrocnemius muscle, metronidazole causes upregulation of Hdac4, myogenin, MuRF1, and atrogin1, which are implicated in skeletal muscle neurogenic atrophy. Metronidazole in SPF mice also upregulates skeletal muscle FoxO3, described as involved in apoptosis and muscle regeneration. Of note, alteration of the gut microbiota results in increased expression of the muscle core clock and effector genes Cry2, Ror-β, and E4BP4. PPARγ and one of its important target genes, adiponectin, are also upregulated by metronidazole. Metronidazole in germ-free (GF) mice increases the expression of other core clock genes, such as Bmal1 and Per2, as well as the metabolic regulators FoxO1 and Pdk4, suggesting a microbiota-independent pharmacologic effect. In conclusion, metronidazole in SPF mice results in skeletal muscle atrophy and changes the expression of genes involved in the muscle peripheral circadian rhythm machinery and metabolic regulation.
ISSN: 1661-6596
DOI: 10.3390/ijms19082418
Rights: © 2018 by The Author(s). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:IGS Journal Articles

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