LAUSR

Gut health is intricately linked with metabolic regulation and physiology. Many factors that drive metabolic changes including dietary patterns like consumption of high salt and/or high-fat diets have a direct effect on the gut (Hasan and Yang, 2019). Despite the widely reported associations between the gut microbiome and cardiometabolic diseases, many gaps remain in the mechanistic links. This Research Topic focuses on the Research Topic “Gut Microbiome and Metabolic Physiology.” The goal of the Research Topic was to highlight studies related to microbiome dysbiosis, metabolism, inflammation, the gut-brain axis, and related chronic diseases (Figure 1). It features 4 manuscripts, highlighted below, that review and investigate novel translational concepts in rodents and humans. Chronic kidney disease affects 37 million American adults and millions more are at risk for developing the disease due to risk factors including diabetes, heart disease, obesity, and hypertension (Kovesdy, 2011). These risk factors share a metabolic dysfunction component in their pathophysiology. Wang et al., explored the link between gut microbiota and chronic kidney disease in association with metabolic dysregulation. The study investigated whether finasteride, a competitive and specific inhibitor of type II 5a-reductase, reduces microbiotaderived trimethylamine N-oxide (TMAO) and alleviates high-fat diet effects in mice with proteinuric nephropathy. TMAO is produced in the liver from trimethylamine which is a gut-derived metabolite of bacterial fermentation of lecithin, choline, L-carnitine, and betaine. The conversion of trimethylamine to TMAO is catalyzed by flavin-containing monooxygenase 3 (Fmo3). Finasteride downregulated Fmo3 and circulating TMAO. Treatment with finasteride maintains tight junction integrity by elevating proteins Claudin-1 and zonulin-1. Finasteride alleviated high fat-associated protein-overload nephropathy and may be a novel therapeutic option to mitigate the pathophysiological relationship between hyperlipidemia and chronic kidney disease progression. The gut communicates with other parts of the body through the many reported axes including the brain. Diseases that affect the central nervous system are associated with gut microbiota dysbiosis (Ma et al., 2019). Li et al., used osthole, a coumarin compound extracted from the natural product Angelica biserrata Yuan et, to target the gut microbiota for the treatment of neuropathic pain. Neuropathic pain was modeled in mice through the fifth and sixth lumbar vertebrae chronic constriction injury (CCI) of the sciatic nerve. They found that CCI was associated with significant changes in the gut microbiota compared to sham mice. Neuropathic pain was associated with higher Bacteriodetes and lower Firmicutes and OPEN ACCESS