Dietary fatty acid composition alters gut microbiome in mice with obesity-induced peripheral neuropathy

Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are increasingly recommended to prevent or slow PN, given multifactorial risks from diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome. Herein, we postulated that SFA- versus MUFA-rich diet will impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes. We found that SFA altered microbiome community structure, which MUFA partially reversed. PN metrics correlated with several microbial families, most significantly and negatively with a microbe of the Bacilli class. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN.