Rifaximin‐altered gut microbiota components associated with liver/neuropsychological functions in patients with hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials

Abstract

AimsRifaximin (RFX), a non‐systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE.MethodsWe analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis.ResultsIn the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test‐A ≥39.55 s and presence of portal‐systemic shunt; (ii) in Veillonella, serum potassium levels <4.75 mEq/L and total cholesterol level <129.5 mg/dL; and (iii) in Lactobacillus, white blood cell counts ≥3.4 × 103/μL and aspartate aminotransferase level ≥44.5 U/L. There was no significant change in total bacterial load before and after RFX treatment; however, there was a decrease in Streptococcus, Veillonella, and Lactobacillus counts after RFX treatment.ConclusionWe report clinical profiles associated with gut bacterial loads in patients with HE, and showed that RFX altered gut microbiota components associated with liver/neuropsychological functions. Thus, RFX could improve liver/neuropsychological functions through the regulation of the gut microbial consortia in patients with HE.

Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain

“…Sung et al [ 43 ] confirmed that fecal microbiota can predict the clinical prognosis of patients with liver cirrhosis and HE, such as Lactobacillus , Bacteroides , Clostridium_incertae_sedisof , and Clostridium XI , which were associated with patients' mortality. Furthermore, Kawaguchi et al [ 172 ] showed that rifaximin improved both liver and neuropsychological function in liver cirrhosis patients with HE by adjusting the gut microbial structure.…”

Genetically engineeredE. coliNissle attenuates hyperammonemia and prevents memory impairment in bile‐duct ligated rats

“…5 Also, the non-absorbable antibiotic rifaximin, which inhibits the activity of urease-producing bacteria, and alters the gut microbiota. 5,6 Nevertheless, the therapeutic response rate to these treatments is not uniform and other therapies are limited. Moreover HE patients often show poor compliance and adherence to these treatments.…”

Efficacy of rifaximin, a poorly absorbed rifamycin antimicrobial agent, for hepatic encephalopathy in Japanese patients

“…Rifaximin has also been reported to shorten the duration of treatment for HE in inpatient settings, resulting in higher cost‐effectiveness of treatment 22 24 Studies on the efficacy of rifaximin and intestinal bacterial flora showed that although total bacterial volume did not change with rifaximin therapy, the volume of Veillonella and Streptococcus species was relatively lower, which suggests that rifaximin might alter intestinal bacterial flora and restore intestinal permeability, thereby reducing neuropsychiatric symptoms 25 26 Given that the therapeutic and prognosis‐improving effects of rifaximin in patients with hepatic cirrhosis have been verified extensively worldwide, 3 , 4 , 9 , 27 and prospective randomized comparative studies cannot be conducted easily, the present results suggest that rifaximin is efficacious for OHE in Japanese patients.…”