dc.contributor.authorManickam, Ravikumar
dc.contributor.authorOh, Hui Yun Penny
dc.contributor.authorTan, Chek Kun
dc.contributor.authorParamalingam, Eeswari
dc.contributor.authorWahli, Walter
dc.identifier.citationManickam, 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/ijms19082418en_US
dc.description.abstractAntibiotics 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.en_US
dc.format.extent14 p.en_US
dc.relation.ispartofseriesInternational Journal of Molecular Sciencesen_US
dc.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 (http://creativecommons.org/licenses/by/4.0/).en_US
dc.subjectGut Dysbiosisen_US
dc.titleMetronidazole causes skeletal muscle atrophy and modulates muscle chronometabolismen_US
dc.typeJournal Article
dc.contributor.schoolInterdisciplinary Graduate School (IGS)en_US
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.description.versionPublished versionen_US
dc.contributor.organizationNTU Institute for Health Technologiesen_US

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