Xiang Kong

and 7 more

Neuroinflammation plays a significant role in pathogenesis of hepatic encephalopathy (HE). Radiotracer [18F]PBR146 is used for in-vivo imaging of neuroinflammation. Bifidobacterium (BIF) and fecal microbiota transplantation (FMT) are emerging as promising therapeutic approaches for HE. The objective of this study was to monitor and compare the treatment efficiencies of BIF and FMT on neuroinflammation in chronic HE rats [bile duct ligation (BDL) operation] by [18F]PBR146 micro-PET/CT. Thirty rats were divided into Sham+NS, BDL+NS, BDL+BIF, and BDL+FMT groups. Behavioral assessments, fecal samples collections, and micro-PET/CT scans were conducted sequentially following the successful establishment of the chronic HE model. The study analyzed average %ID/g values of whole brain, brain regions, and main organs across each group, complemented by biochemical and pathological analysis. Behavioral results, IL-1β, IL-6, IL-10, and TNF-α levels showed no significant differences among four groups. Although there was no significant difference in global brain uptake values of [18F]PBR146 among four groups (P=0.053), regional brain comparisons revealed significant discrepancies in bilateral accumbens, retrosplenial cortex, posterior hippocampus, left striatum, cingulate cortex, right frontal association cortex, and antero-dorsal hippocampus (all P<0.05). Sham+NS group was mainly enriched with Parasutterella, Streptococcus, and Anaeroplasma, the BDL+FMT group with Enterococcus, Aestuariispira, Lactobacillus, Pseudomonas, and Globicatella, and the BDL+BIF group with Enterorhabdus. The results suggested that BIF had inhibitory effect on neuroinflammation in BDL rats, whereas FMT did not demonstrate positive effects on the chronic HE model rats, might because of dysbiosis. [18F]PBR146 could effectively and noninvasively monitor the efficacy of gut-targeted treatment in chronic HE model.