Curcumin monoglucuronide (CMG) treatment differentially affects gut microbiota at three anatomical sites, modulating neuroinflammation

We developed a prodrug type of curcumin, curcumin monoglucuronide (CMG), whose injection achieves a high serum concentration of free-form curcumin. Although curcumin has been reported to potentially alter gut microbiota and immune responses, it is unclear whether the altered microbiota could be associated with inflammation in immune-mediated diseases. We aimed to determine the extent of which CMG treatment could affect gut microbiota at three anatomical sites (feces, ileal contents, and the ileal mucosa), leading to suppression of inflammation in the central nervous system (CNS) in an autoimmune model for multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). We treated EAE mice with CMG, harvested the CNS tissues for histological analyses, and conducted microbiome analyses using 16S rRNA sequencing. CMG treatment ameliorated EAE, clinically and histologically, and altered overall microbiota composition in feces and ileal contents, but not the ileal mucosa. Principal component analysis (PCA) of the microbiome showed that principal component (PC) 1 values in the ileal content, but not feces, were correlated with clinical and histological EAE scores. On the other hand, when we analyzed the individual bacteria of the microbiota, the EAE scores were correlated with significant increases in relative abundance of two bacterial species at each anatomical site. Therefore, CMG treatment could differentially alter gut microbiota at three different sites in not only overall gut microbiome compositions, but also abundance of individual bacteria, each of which associated with modulation of inflammation in the CNS.