Altered Gut Microbiota Related to Inflammatory Responses in Patients With Huntington's Disease

Front Immunol. 2021 Feb 19:11:603594. doi: 10.3389/fimmu.2020.603594. eCollection 2020.

Abstract

Emerging evidence indicates that gut dysbiosis may play a regulatory role in the onset and progression of Huntington's disease (HD). However, any alterations in the fecal microbiome of HD patients and its relation to the host cytokine response remain unknown. The present study investigated alterations and host cytokine responses in patients with HD. We enrolled 33 HD patients and 33 sex- and age- matched healthy controls. Fecal microbiota communities were determined through 16S ribosomal DNA gene sequencing, from which we analyzed fecal microbial richness, evenness, structure, and differential abundance of individual taxa between HD patients and healthy controls. HD patients were evaluated for their clinical characteristics, and the relationships of fecal microbiota with these clinical characteristics were analyzed. Plasma concentrations of interferon gamma (IFN-γ), interleukin 1 beta (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor alpha were measured by Meso Scale Discovery (MSD) assays, and relationships between microbiota and cytokine levels were analyzed in the HD group. HD patients showed increased α-diversity (richness), β-diversity (structure), and altered relative abundances of several taxa compared to those in healthy controls. HD-associated clinical characteristics correlated with the abundances of components of fecal microbiota at the genus level. Genus Intestinimonas was correlated with total functional capacity scores and IL-4 levels. Our present study also revealed that genus Bilophila were negatively correlated with proinflammatory IL-6 levels. Taken together, our present study represents the first to demonstrate alterations in fecal microbiota and inflammatory cytokine responses in HD patients. Further elucidation of interactions between microbial and host immune responses may help to better understand the pathogenesis of HD.

Keywords: 16S rDNA; Huntington’s disease; cytokines; gut microbiota; neuroinflammation.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacteria / genetics
  • Bacteria / immunology*
  • Case-Control Studies
  • China
  • Cytokines / blood*
  • Dysbiosis
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome*
  • Host-Pathogen Interactions
  • Humans
  • Huntington Disease / blood
  • Huntington Disease / diagnosis
  • Huntington Disease / immunology
  • Huntington Disease / microbiology*
  • Inflammation Mediators / blood*
  • Intestines / microbiology*
  • Male
  • Middle Aged
  • Phylogeny
  • Ribotyping

Substances

  • Cytokines
  • Inflammation Mediators