Rifaximin ameliorates hepatic encephalopathy and endotoxemia without affecting the gut microbiome diversity.

Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Internet ISSN: 2219-2840 (Electronic) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE

Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group
Original Publication: Beijing : WJG Press, c1998-

Anti-Bacterial Agents/*therapeutic use ; Endotoxemia/*drug therapy ; Gastrointestinal Microbiome/*drug effects ; Hepatic Encephalopathy/*drug therapy ; Liver Cirrhosis/*complications ; Rifamycins/*therapeutic use; Aged ; Aged, 80 and over ; Ammonia/blood ; Ammonia/toxicity ; Anti-Bacterial Agents/pharmacology ; Case-Control Studies ; Cognition/drug effects ; Endotoxemia/etiology ; Endotoxins/blood ; Endotoxins/toxicity ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/physiology ; Hepatic Encephalopathy/blood ; Hepatic Encephalopathy/etiology ; Humans ; Liver Cirrhosis/blood ; Male ; Middle Aged ; Neuropsychological Tests ; Rifamycins/pharmacology ; Rifaximin ; Treatment Outcome

Aim: To determine the efficacy of rifaximin for hepatic encephalopathy (HE) with the linkage of gut microbiome in decompensated cirrhotic patients.
Methods: Twenty patients (12 men and 8 women; median age, 66.8 years; range, 46-81 years) with decompensated cirrhosis (Child-pugh score > 7) underwent cognitive neuropsychological testing, endotoxin analysis, and fecal microbiome assessment at baseline and after 4 wk of treatment with rifaximin 400 mg thrice a day. HE was determined by serum ammonia level and number connection test (NCT)-A. Changes in whole blood endotoxin activity (EA) was analyzed by endotoxin activity assay. Fecal microbiome was assessed by 16S ribosome RNA (rRNA) gene sequencing.
Results: Treatment with rifaximin for 4 wk improved hyperammonemia (from 90.6 ± 23.9 μg/dL to 73.1 ± 33.1 μg/dL; P < 0.05) and time required for NCT (from 68.2 ± 17.4 s to 54.9 ± 20.3 s; P < 0.05) in patients who had higher levels at baseline. Endotoxin activity was reduced (from 0.43 ± 0.03 to 0.32 ± 0.09; P < 0.05) in direct correlation with decrease in serum ammonia levels ( r = 0.5886, P < 0.05). No statistically significant differences were observed in the diversity estimator (Shannon diversity index) and major components of the gut microbiome between the baseline and after treatment groups (3.948 ± 0.548 at baseline vs 3.980 ± 0.968 after treatment; P = 0.544), but the relative abundances of genus Veillonella and Streptococcus were lowered.
Conclusion: Rifaximin significantly improved cognition and reduced endotoxin activity without significantly affecting the composition of the gut microbiome in patients with decompensated cirrhosis.
Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.

Aliment Pharmacol Ther. 2016 Jan;43 Suppl 1:11-26. (PMID: 26618922)
PLoS One. 2013;8(4):e60042. (PMID: 23565181)
Hepatology. 2011 Aug;54(2):562-72. (PMID: 21574172)
World J Gastroenterol. 2015 Nov 7;21(41):11815-24. (PMID: 26557005)
Inflamm Intest Dis. 2016 Apr;1(1):3-8. (PMID: 27243019)
Chemotherapy. 2005;51 Suppl 1:67-72. (PMID: 15855749)
J Hepatol. 2014 May;60(5):940-7. (PMID: 24374295)
Hepatology. 2004 May;39(5):1441-9. (PMID: 15122774)
Am J Gastroenterol. 2008 Jul;103(7):1707-15. (PMID: 18691193)
J Clin Exp Hepatol. 2015 Mar;5(Suppl 1):S21-8. (PMID: 26041953)
Aliment Pharmacol Ther. 2014 Jul;40(2):123-32. (PMID: 24849268)
Int J Antimicrob Agents. 2010 Mar;35(3):278-81. (PMID: 20045287)
Sci Rep. 2016 May 26;6:26800. (PMID: 27225869)
J Gastroenterol Hepatol. 2018 Jan;33(1):307-314. (PMID: 28671712)
Clin Transl Gastroenterol. 2016 Aug 25;7(8):e187. (PMID: 27560928)
Appl Environ Microbiol. 2007 Aug;73(16):5261-7. (PMID: 17586664)
Mol Med Rep. 2015 Mar;11(3):1693-700. (PMID: 25421042)
Hepatology. 2017 Dec;66(6):1727-1738. (PMID: 28586116)
Front Pharmacol. 2016 May 09;7:120. (PMID: 27242527)
Nat Rev Gastroenterol Hepatol. 2010 Sep;7(9):515-25. (PMID: 20703237)
Hepatology. 2007 Jun;45(6):1517-26. (PMID: 17523148)
World J Hepatol. 2015 Mar 27;7(3):425-42. (PMID: 25848468)
Nature. 2014 Sep 4;513(7516):59-64. (PMID: 25079328)
Crit Care. 2002 Aug;6(4):342-8. (PMID: 12225611)
Brief Bioinform. 2012 Nov;13(6):656-68. (PMID: 22772836)
N Engl J Med. 2010 Mar 25;362(12):1071-81. (PMID: 20335583)
J Hepatol. 2005;42 Suppl(1):S45-53. (PMID: 15777572)
Gastroenterology. 1978 Sep;75(3):462-9. (PMID: 680502)
Life Sci. 2011 Dec 5;89(23-24):847-53. (PMID: 21958471)
Am J Physiol Gastrointest Liver Physiol. 2012 Sep 15;303(6):G675-85. (PMID: 22821944)
Bone Marrow Transplant. 2013 Mar;48(3):452-8. (PMID: 23208313)
J Hepatol. 2012 Apr;56(4):893-9. (PMID: 22173161)
Hepatol Res. 2017 Nov;47(12 ):1335-1339. (PMID: 28066966)
Brain Behav Immun. 2006 Sep;20(5):449-55. (PMID: 16309883)
Gut Microbes. 2014 May-Jun;5(3):397-403. (PMID: 24690956)
J Hepatol. 2002 Oct;37(4):456-62. (PMID: 12217598)
Appl Environ Microbiol. 2009 Dec;75(23):7537-41. (PMID: 19801464)
Hepatology. 2009 Dec;50(6):2014-21. (PMID: 19787808)
Chemotherapy. 2005;51 Suppl 1:36-66. (PMID: 15855748)
J Inflamm (Lond). 2013 Mar 06;10(1):8. (PMID: 23510603)
Arch Oral Biol. 1975 Jul;20(7):407-10. (PMID: 1096856)
Hepatology. 2005 May;41(5):1065-73. (PMID: 15830392)
Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G168-75. (PMID: 21940902)

Keywords: Endotoxin; Gut microbiome; Hepatic encephalopathy; Liver cirrhosis; Rifaximin

0 (Anti-Bacterial Agents)
0 (Endotoxins)
0 (Rifamycins)
7664-41-7 (Ammonia)
L36O5T016N (Rifaximin)

Date Created: 20180109 Date Completed: 20180808 Latest Revision: 20220409

20221213

PMC5743506

10.3748/wjg.v23.i47.8355

29307995