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Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice.

Abstract：

:Obesity affects over 2 billion people worldwide and is accompanied by peripheral neuropathy (PN) and an associated poorer quality of life. Despite high prevalence, the molecular mechanisms underlying the painful manifestations of PN are poorly understood, and therapies are restricted to use of painkillers or other drugs that do not address the underlying disease. Studies have demonstrated that the gut microbiome is linked to metabolic health and its alteration is associated with many diseases, including obesity. Pathologic changes to the gut microbiome have recently been linked to somatosensory pain, but any relationships between gut microbiome and PN in obesity have yet to be explored. Our data show that mice fed a Western diet developed indices of PN that were attenuated by concurrent fecal microbiome transplantation (FMT). In addition, we observed changes in expression of genes involved in lipid metabolism and calcium handling in cells of the peripheral nerve system (PNS). FMT also induced changes in the immune cell populations of the PNS. There was a correlation between an increase in the circulating short-chain fatty acid butyrate and pain improvement following FMT. Additionally, butyrate modulated gene expression and immune cells in the PNS. Circulating butyrate was also negatively correlated with distal pain in 29 participants with varied body mass index. Our data suggest that the metabolite butyrate, secreted by the gut microbiome, underlies some of the effects of FMT. Targeting the gut microbiome, butyrate, and its consequences may represent novel viable approaches to prevent or relieve obesity-associated neuropathies.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Bonomo RR,Cook TM,Gavini CK,White CR,Jones JR,Bovo E,Zima AV,Brown IA,Dugas LR,Zakharian E,Aubert G,Alonzo F 3rd,Calcutt NA,Mansuy-Aubert V

doi

10.1073/pnas.2006065117

subject

Has Abstract

pub_date

2020-10-20 00:00:00

pages

26482-26493

issue

eissn

0027-8424

issn

1091-6490

pii

2006065117

journal_volume

117

pub_type

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Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice.