Gut microbiota has recently emerged as a major regulator of energy utilization, glycemia and immunological function. Disturbances in gut microbiota have been widely reported in obesity and type 2 diabetes (T2D). We have previously shown that dietary reversal (DR) alleviates peripheral neuropathy (PN), a common complication of obesity and T2D. However, the crosstalk between the microbiome, nerve function, and DR in PN remains unknown. Therefore, the objective of this study was to identify the changes in gut microbiome and correlate them with PN phenotypes during disease progression and reversal in a mouse model of obesity, prediabetes, and PN. The study consisted of five groups of C57BL6/J mice: mice were fed a standard diet (10% kcal fat; SD) or a high-fat diet (60% kcal fat; HFD) from 5-16 wk. of age, mice fed a SD or HFD from 5-24 wk., and mice fed a HFD from 5-16 wk. then switched to SD from 16-24 wk. (DR). Fecal samples were collected bi-weekly and gut tissue content at 16 or 24 wk along with metabolic and neuropathy phenotypes measured at the same time. Bacterial communities were profiled by 16S rRNA gene V3-V4 sequencing from cecum, colon, ileum, and fecal samples. Amplicon sequence variants were determined and taxonomically classified against the SILVA database. We observed significant changes in the gut microbial community structure soon after HFD was introduced, which was restored following DR. These changes were driven by bacterial families belonging to the Firmicutes (Lactobacillaceae and Clostridiales Family XIII), which were increased by HFD and subsequently decreased by DR. Notably, the distinct microbiota profiles were significantly correlated with HFD-induced PN and its reversal by DR. Our results provide new insights into the role of gut microbiota in the development of PN and highlight the potential therapeutic efficacy of a dietary intervention in restoring the microbiome and improving nerve function.


K. Guo: None. C. Figueroa-Romero: None. S. Eid: None. L.M. Hinder: None. H.J. Petit: None. J. Hur: None. E.L. Feldman: Consultant; Self; Novartis Pharmaceuticals Corporation.


National Institutes of Health (R24DK082841)

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