The neuroinflammation imaging of bifidobacterium and fecal microbiota transplantation: therapeutic effects evaluation in chronic hepatic encephalopathy rats by [18F]PBR146 in-vivo imaging

Abstract

Abstract Neuroinflammation is an important pathogenesis of hepatic encephalopathy (HE). The radiotracer [18F]PBR146 targeted to translocator protein (TSPO) is been applied for neuroinflammation vivo-imaging. Bifidobacterium (BIF) and fecal microbiota transplantation (FMT) are promising therapeutic approaches for HE. The purpose of this study was to in vivo monitor and compare BIF and FMT treatment efficiencies on neuroinflammation in chronic HE rats by [18F]PBR146 micro-PET/CT. Bile duct ligation (BDL) operation was performed in male rats to induce chronic HE. Thirty rats were divided into Sham + NS, BDL + NS, BDL + BIF, and BDL + FMT groups. Behavioral assessment, fecal samples collection, and micro-PET/CT scans were performed sequentially after chronic HE model successful established. We analyzed the average %ID/g values of whole brain, brain regions, and main organs in each group rats, and performed biochemical and pathological analysis. The mortality of BDL operated rats was 25% (6/24). The behavior results showed no significant difference among groups except rotarod test result. The plasma IL-1β, IL-6, IL-10, and TNF-α levels had no differences among 4 groups except 5-HT and IFN-γ. Although global brain uptake values of [18F]PBR146 had no significant difference among 4 groups (P = 0.053), the regional brain comparison showed that bilateral accumbens, retrosplenial cortex, posterior hippocampus, left striatum, cingulate cortex, right frontal association cortex, antero-dorsal hippocampus had significant differences among groups (all P < 0.05). Sham + NS group was mainly enriched in Parasutterella, Streptococcus, and Anaeroplasma, BDL + FMT group was mainly enriched in Enterococcus, Aestuariispira, Lactobacillus, Pseudomonas, and Globicatella, BDL + BIF group was enriched in Enterorhabdus. The results show that BIF had inhibitory effect to neuroinflammation of BDL rats, while FMT showed no positive effects to chronic HE model rats might because of dysbiosis. [18F]PBR146 could effectively and noninvasively monitor gut-targeted treatment efficacy of chronic HE model.