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

Abstract

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, p = 0.023; ΔsMR: R = 0.613, p = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus 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.

Furosemide as a factor to deteriorate therapeutic efficacy of rifaximin in patients with decompensated cirrhosis

“…Kaji et al reported that rifaximin decreased circulatory endotoxin levels through improvement of intestinal hyperpermeability, 26 suggesting that long-term rifaximin treatment could improve liver function. In the present study, however, liver function tests, except for serum ammonia levels, did not improve significantly during the observation period.…”

From intestinal dysbiosis to alcohol-associated liver disease

“…35,36 Currently, norfloxacin and rifaximin are the forms of selective intestinal decontamination for which there is the most evidence in cirrhosis. [37][38][39] However, the major drawback of routine antibiotic prophylaxis is the emergence of multidrug-resistant organisms. 34 Thus, novel therapies have been proposed based on their ability to modify the altered intestinal microbiota such as probiotics and prebiotics, 19,[40][41][42][43][44][45] fecal microbiota transplantation, 46,47 phage therapy, 31 among others.…”

New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action

“…The development and validation of antimicrobials also encompass the evaluation of their in vivo efficacy and side effects. In the paper of Kaji et al, the effects of rifaximin on the gut microbiome were investigated [18]. Rifaximin is an antibiotic used to hepatic encephalopathy, a disease comprising a wide range of neurological and psychiatric manifestations [18].…”

“…In the paper of Kaji et al, the effects of rifaximin on the gut microbiome were investigated [18]. Rifaximin is an antibiotic used to hepatic encephalopathy, a disease comprising a wide range of neurological and psychiatric manifestations [18]. The study was based on 16S rRNA gene sequencing to assess alterations in the microbiota of fecal samples from 30 patients before and after rifaximin treatment [18].…”

“…Rifaximin is an antibiotic used to hepatic encephalopathy, a disease comprising a wide range of neurological and psychiatric manifestations [18]. The study was based on 16S rRNA gene sequencing to assess alterations in the microbiota of fecal samples from 30 patients before and after rifaximin treatment [18]. Although the study only gathered a limited number of samples, the results indicate that rifaximin led to minor changes in patients' intestinal microbiota [18].…”