Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice

Abstract

The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.

Gut microbiota and acne: A Mendelian randomization study

“…According to the widely accepted theory of the gut‐skin axis, the mechanism by which the gut microbiota influences acne may be associated with the inflammatory immune response 51 . The abundance of Allisonella is significantly increased in patients with Down syndrome and is positively associated with the levels of proinflammatory cytokines 52 . According to a reported study, Bacteroides were found to stimulate macrophages and monocytes to secrete the proinflammatory cytokine TNFα through an LPS‐mediated pathway 53 .…”

“… 51 The abundance of Allisonella is significantly increased in patients with Down syndrome and is positively associated with the levels of proinflammatory cytokines. 52 According to a reported study, Bacteroides were found to stimulate macrophages and monocytes to secrete the proinflammatory cytokine TNFα through an LPS‐mediated pathway. 53 Medium‐chain triglycerides (MCT) improve the immune status by increasing the abundance of Fusicatenibacter in the intestinal flora.…”