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.
Highlights
Genetic components are the dominant factors in the pathogeneses of monogenic neurodegenerative diseases
The present study provides the evidence for gut dysbiosis in human patients with Huntington’s disease (HD), providing clinical relevance to a previous study that reported gut dysbiosis in a transgenic mouse model of HD [11]
We found that Intestinimonas and Bilophila correlated with concentrations of IL-4 and IL-6, respectively, in HD patients, suggesting the occurrence of a systemic chronic inflammatory status associated with altered gut microbiota
Summary
Genetic components are the dominant factors in the pathogeneses of monogenic neurodegenerative diseases. At present, increased attention has been focused on the role of the gut–brain axis and its related humoral response in the development of neurodegenerative diseases. The role of the gut– brain axis in monogenic neurodegenerative disease remains unclear. HD is caused by the expansion of CAG trinucleotide repeats in exon 1 of the huntingtin (HTT) gene on chromosome 4, and HTT is widely expressed in the brain and in peripheral tissues such as skeletal muscles and the gut [1,2,3,4]. The mutant huntingtin (mHTT) protein, which is expressed in the gastrointestinal (GI) tract, causes GI dysfunction, including impaired gut motility, diarrhea, and malabsorption of food [5]. MHTT is expressed in peripheral myeloid cells, including monocytes and macrophages [12, 13]. Monocytes from the blood of HD patients produce increased levels of cytokines ex vivo when stimulated [13, 14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
