Rifaximin Alleviates Endotoxemia with Decreased Serum Levels of Soluble CD163 and Mannose Receptor and Partial Modification of Gut Microbiota in Cirrhotic Patients

• Main Authors: Kosuke Kaji, Soichiro Saikawa, Hiroaki Takaya, Yukihisa Fujinaga, Masanori Furukawa, Koh Kitagawa, Takahiro Ozutsumi, Daisuke Kaya, Yuki Tsuji, Yasuhiko Sawada, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Akira Mitoro, Hitoshi Yoshiji
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Antibiotics
• Subjects: cirrhosis; endotoxin; microbiome; rifaximin
• Online Access: https://www.mdpi.com/2079-6382/9/4/145

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (ΔsCD163: Correlation coefficient (R) = 0.680, <i>p</i> = 0.023; ΔsMR: R = 0.613, <i>p</i> = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the <i>Streptococcus</i> genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change.