Gut microbiome and its potential role in obesity‐induced neuropathy

Abstract

Obesity is considered a 21st century epidemic, affecting over 2 billion people worldwide1. This condition is often accompanied by several complications, including peripheral neuropathy (PN). PN is a highly prevalent disease, characterized by a distal‐to proximal nerve degeneration with current no available treatment2. The initial stages of PN are clinically presented as peripheral tactile allodynia and thermal hyperalgesia, that later progress to numbness and loss of sensation3. Despite high prevalence, the molecular mechanisms underlying the disease onset are poorly understood, and affected patients have no choice other than to use pain killers. Using sensory neurons‐specific transgenic mice, we observed expression of short chain fatty acid receptors (FFAR) at the surface of neurons expressing Nav1.8 (sensory neurons proven to be involved in type II diabetes painful neuropathy4,5). Because, short chain fatty acids are metabolites secreted by gut bacteria, this data potentially links the microbiome with obesity‐induced pain. Numerous studies have demonstrated that the gut microbiome may play a role in the development of obesity and its associated comorbidities6. Moreover, fecal microbiome transplantation (FMT) has been used to treat innumerous metabolic disorders7. Still, the relationship between gut microbiome and PN onset and progression has yet to be explored. To investigate whether gut microbiome is involved in allodynia onset and/or progression in obesity, we utilized an obesity‐induced allodynia mouse model developed in our lab. Our results show that mice fed Western diet (WD) had reduced mechanical allodynia and thermal sensitivity threshold when compared to mice fed normal chow (NC). Our data showed that WD fed mice subjected to FMT, exhibited improved mechanical and thermal sensitivity when compared to WD alone and respective control groups. In addition, glucose tolerance was improved in the aforementioned groups. We also evaluated changes in i) gut bacterial composition following FMT, assessed by 16S sequencing, ii) in plasma short chain fatty acid and iii) in the gene expression in neurons of the dorsal root ganglia and sciatic nerve. In summary, the data presented shows that transplantation of gut bacteria from lean mice to WD‐fed mice improve PN symptoms in obese mice. Our data also suggest that the gut microbiome metabolites may change sensory neurons function via modulating short chain fatty acid receptor located at the surface of sensory neurons. This line of study could provide alternative therapeutic targets to replace the use of addictive pain killers. The gut microbiome, its metabolites and short chain fatty acid receptors could be a novel valuable target to study the delay or cure of debilitating pain associated with obesity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.