Veeravalli, Sunil, Varshavi, Dorsa, Scott, Flora H, Varshavi, Dorna, Pullen, Francis, Veselkov, Kirill, Phillips, Ian R, Everett, Jeremy ORCID: 0000-0003-1550-4482 and Shephard, Elizabeth (2022) Treatment of wild-type mice with 2,3-butanediol, a urinary biomarker of Fmo5-/- mice, decreases plasma cholesterol and epididymal fat deposition. Frontiers in Physiology, 13:859681. pp. 1-13. ISSN 1664-042X (Online) (doi:https://doi.org/10.3389/fphys.2022.859681)

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Abstract

We previously showed that Fmo5-/- mice exhibit a lean phenotype and slower metabolic ageing. Their characteristics include lower plasma glucose and cholesterol, greater glucose tolerance and insulin sensitivity, and a reduction in age-related weight gain and whole-body fat deposition. In this paper, nuclear magnetic resonance (NMR) spectroscopy-based metabolite analyses of the urine of Fmo5-/- and wild-type mice identified two isomers of 2,3-butanediol as discriminating urinary biomarkers of Fmo5-/- mice. Antibiotic-treatment of Fmo5-/- mice increased plasma cholesterol concentration and substantially reduced urinary excretion of 2,3-butanediol isomers, indicating that the gut microbiome contributed to the lower plasma cholesterol of Fmo5-/- mice, and that 2,3-butanediol is microbially derived. Short- and long-term treatment of wild-type mice with a 2,3-butanediol isomer mix decreased plasma cholesterol and epididymal fat deposition but had no effect on plasma concentrations of glucose or insulin, or on body weight. In the case of long-term treatment, the effects were maintained after withdrawal of 2,3-butanediol. Short-, but not long-term treatment, also decreased plasma concentrations of triglycerides and non-esterified fatty acids. Fecal transplant from Fmo5-/- to wild-type mice had no effect on plasma cholesterol, and 2,3-butanediol was not detected in the urine of recipient mice, suggesting that the microbiota of the large intestine was not the source of 2,3-butanediol. However, 2,3-butanediol was detected in the stomach of Fmo5-/- mice, which was enriched for Lactobacillus genera, known to produce 2,3-butanediol. Our results indicate a microbial contribution to the phenotypic characteristic of Fmo5-/- mice of decreased plasma cholesterol and identify 2,3-butanediol as a potential agent for lowering plasma cholesterol.

Item Type:	Article
Additional Information:	Patent WO 2021/038253 A1 filed 01 September 2019.
Uncontrolled Keywords:	antibiotic; gut microbiome; metabolite; NMR (nuclear magnetic resonance) spectroscopy; stomach; urine
Subjects:	R Medicine > RS Pharmacy and materia medica T Technology > TP Chemical technology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > Medway Centre for Pharmaceutical Science > Pharmaceutical and Medicinal Science Research Group Faculty of Engineering & Science > Medway School of Pharmacy Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	19 Nov 2024 14:34
URI:	http://gala.gre.ac.uk/id/eprint/37467

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