Gut microbiota and metabolome in sporadic Creutzfeldt-Jakob disease

Abstract

Background: Gut dysbiosis and the resulting changes in the metabolites have been associated with neurological diseases. However, the relationship between the gut microbiota and sporadic Creutzfeldt-Jakob disease (sCJD) need to be clarified. The aim of this study was to evaluate the changes in the composition of gut microbiota and metabolome accompanying sCJD, and determine their correlation with disease severity.

Methods: Fecal samples were collected from 25 sCJD patients and 23 healthy controls. The composition of the fecal microbiota and metabolites was respectively analyzed by 16S ribosomal RNA sequencing and untargeted metabolomics. The correlation of gut microbiota and metabolites with MMSE, MoCA and MRC scores was analyzed.

Results: The sCJD patients showed significant differences in the composition of gut microbiota and metabolites relative to the healthy controls. Several bacteria taxa in sCJD patients were increased at genus level, such as Turicibacter, norank_f_Christensenellaceae, Eisenbergiella, Bilophila and Holdemania. A total of 547 differential metabolites were identified between these two groups (VIP > 1, FDR p < 0.05). As per KEGG analysis, the metabolites related to the biosynthesis of phenylpropanoids, especially biochanin A, showed the most obvious decrease in the sCJD group. In addition, most metabolites involved in the pathways related to linoleic acid metabolism and steroid hormone biosynthesis were associated with MRC scale.

Conclusion: Our findings provide new insights into the relationship between gut microbiota and metabolites and sCJD. Some compounds, especially those related to the biosynthesis of phenylpropanoids were significantly altered in patients with sCJD, and those related to linoleic acid metabolism and steroid hormone biosynthesis might be biomarkers of evaluating disease severity.

Keywords: Creutzfeldt–Jakob disease; Gut metabolites; Gut microbiota; Metabonomics.