Evidence map›Paper›PMID 27560928›Full record

ArticleClinical and translational gastroenterology2016

Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition.

Dae J Kang, Genta Kakiyama, Naga S Betrapally, Jeremy Herzog, Hiroshi Nittono, Phillip B Hylemon, Huiping Zhou, Ian Carroll, Jing Yang, Patrick M Gillevet and 11 more

Open access · goldAbstract read
In one paragraph

Article in Clinical and translational gastroenterology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 2 pooled it
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.

  1. Efficacy and Safety of Rifaximin in the Prevention of Recurrent Episodes of Hepatic Encephalopathy: A Systematic Review and Meta-analysis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2023
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  11. A Randomized Trial of Rifaximin vs Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet for Symptom Outcomes and Microbiome Changes in Irritable Bowel Syndrome.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026
    Article
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  15. A Review of Recent Advances in Fecal Microbiota Transplantation for the Treatment of Hepatic Encephalopathy.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Review
  16. Microbial Approaches to Treat and Prevent Hepatic Encephalopathy.Gastroenterology clinics of North America · 2025
    Review
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2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 2 countries.

Dae J KangDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Genta KakiyamaDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Naga S BetrapallyMicrobiome Analysis Center, George Mason University, Manassas, Virginia, USA.
Jeremy HerzogDepartment of Medicine, University of North Carolina, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina, USA.
Hiroshi NittonoJunshin Clinic Bile Acid Institute, Tokyo, Japan.
Phillip B HylemonDepartment of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Huiping ZhouDepartment of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Ian CarrollMicrobiome Analysis Center, George Mason University, Manassas, Virginia, USA.
Jing YangDepartment of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Patrick M GillevetMicrobiome Analysis Center, George Mason University, Manassas, Virginia, USA.
Chunhua JiaoDepartment of Microbiology and Immunology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Hajime TakeiJunshin Clinic Bile Acid Institute, Tokyo, Japan.
William M PandakDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Takashi IidaDepartment of Chemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan.
Douglas M HeumanDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Sili FanWest Coast Metabolomics Center, University of California, Davis, California, USA.
Oliver FiehnWest Coast Metabolomics Center, University of California, Davis, California, USA.
Takao KurosawaSchool of Pharmaceutical Science, Health Sciences University of Hokkaido, Tobetsu, Japan.
Masoumeh SikaroodiMicrobiome Analysis Center, George Mason University, Manassas, Virginia, USA.
R B SartorDepartment of Medicine, University of North Carolina, Division of Gastroenterology and Hepatology, Chapel Hill, North Carolina, USA.
Jasmohan S BajajDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA.
Hunter Holmes McGuire VA Medical Center · USGeorge Mason University · USVirginia Commonwealth University · USTokyo Junshin University · JPUniversity of California, Davis · USUniversity of North Carolina at Chapel Hill · USHealth Sciences University of Hokkaido · JPNihon University · JP

Funding

PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
National Gnotobiotic Rodent Resource CenterP40OD010995 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ryan B Sartor · 2012 to 2026
$9.7M
Spectrum of Neuro-Cognitive Impairment in CirrhosisR01DK087913 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI BAJAJ, JASMOHAN S · 2011 to 2015
$2.0M
Role of Bile Acids and Gut Bacteria in GI DiseasesI01BX001328 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI HYLEMON, PHILLIP B · 2012 to 2020
–
Fecal Microbiota Transplant in Veterans with CirrhosisI01CX001076 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI BAJAJ, JASMOHAN S · 2015 to 2024
–
BLRD VA I01 BX000197BLRD VA I01 BX001328CSRD VA I01 CX001076NIDDK NIH HHS P30 DK034987NIDDK NIH HHS R01 DK087913NIH HHS P40 OD010995
6 · The paper itself

Abstract

objectivesRifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin.

methodsFour germ-free (GF) mice groups were used (1) GF, (2) GF+rifaximin, (3) Humanized with stools from an MHE patient, and (4) Humanized+rifaximin. Mice were followed for 30 days while rifaximin was administered in chow at 100 mg/kg from days 16-30. We tested for ammonia generation (small-intestinal glutaminase, serum ammonia, and cecal glutamine/amino-acid moieties), systemic inflammation (serum IL-1β, IL-6), intestinal barrier (FITC-dextran, large-/small-intestinal expression of IL-1β, IL-6, MCP-1, e-cadherin and zonulin) along with microbiota composition (colonic and fecal multi-tagged sequencing) and function (endotoxemia, fecal bile acid deconjugation and de-hydroxylation).

resultsAll mice survived until day 30. In the GF setting, rifaximin decreased intestinal ammonia generation (lower serum ammonia, increased small-intestinal glutaminase, and cecal glutamine content) without changing inflammation or intestinal barrier function. Humanized microbiota increased systemic/intestinal inflammation and endotoxemia without hyperammonemia. Rifaximin therapy significantly ameliorated these inflammatory cytokines. Rifaximin also favorably impacted microbiota function (reduced endotoxin and decreased deconjugation and formation of potentially toxic secondary bile acids), but not microbial composition in humanized mice.

conclusionsRifaximin beneficially alters intestinal ammonia generation by regulating intestinal glutaminase expression independent of gut microbiota. MHE-associated fecal colonization results in intestinal and systemic inflammation in GF mice, which is also ameliorated with rifaximin.

Identifiers

PMID27560928
PMCPMC5543406
OpenAlexW2511281246

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.