Efficacies of Bifidobacterium and Fecal Microbiota Transplantation in Rats With Chronic Hepatic Encephalopathy Assessed by [ ¹⁸ F]PBR146 Imaging of Neuroinflammation

Neuroinflammation significantly contributes to hepatic encephalopathy (HE). The radiotracer [¹⁸F]PBR146 is used for in vivo imaging of neuroinflammation. Promising treatments like Bifidobacterium (BIF) and fecal microbiota transplantation (FMT) are being explored for HE. This study evaluated and compared the efficacies of BIF and FMT in reducing neuroinflammation in chronic HE rats induced by bile duct ligation (BDL) using [¹⁸F]PBR146 micro-PET/CT imaging. Thirty rats were divided into four groups: (1) Sham-operated rats received normal saline (Sham + NS group), (2) BDL rats treated with NS (BDL + NS group), (3) BDL rats administered with BIF (BDL + BIF group), and (4) BDL rats administered with FMT (BDL + FMT group). Following the establishment of the chronic HE model, we conducted sequential behavioral assessments, collected fecal samples, and performed micro-PET/CT scans. Data analysis included average %ID/g values across the whole brain and specific regions, alongside biochemical and pathological evaluations. No significant differences in behavioral results or levels of IL-1β, IL-6, IL-10, and TNF-α were found among the groups. While there was no significant difference in global brain uptake values of [¹⁸F]PBR146 among the four groups (p = 0.053), regional analyses showed significant discrepancies in areas such as the bilateral accumbens and retrosplenial cortex. The Sham + NS group was enriched with Parasutterella, Streptococcus, and Anaeroplasma, the BDL + FMT group had Enterococcus, Aestuariispira, Lactobacillus, Pseudomonas, and Globicatella, while the BDL + BIF group contained Enterorhabdus. Results indicated that BIF inhibited neuroinflammation in BDL rats, whereas FMT showed no positive effects, possibly due to dysbiosis. Notably, [¹⁸F]PBR146 could effectively and noninvasively monitor the efficacies of gut-targeted treatments in chronic HE models.