The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Modulation of the Metabiome by Rifaximin in Patients with Cirrhosis and Minimal Hepatic Encephalopathy
Open accessAbstract
UNLABELLED: Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. METHODS: Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. RESULTS: There was a significant improvement in cognition(six of seven tests improved, p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa remained similar. CONCLUSIONS: Rifaximin is associated with improved cognitive function and endotoxemia in MHE, which is accompanied by alteration of gut bacterial linkages with metabolites without significant change in microbial abundance. TRIAL REGISTRATION: ClinicalTrials.gov NCT01069133.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Administration of non-absorbable antibiotics in patients with hepatic encephalopathy and mild cognitive impairment improves cognitive performance, subcortical brain activity, fronto-parietal connectivity, and serum metabolomic profile (418, 419).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [419]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
PLS-regression: a basic tool of chemometrics
Wold, S., Sjöström, M., & Eriksson, L. (2001) · Chemometrics and Intelligent Laboratory Systems · doi:10.1016/s0169-7439(01)00155-1 · Cited by 10,084
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548
Ferenci, P., Lockwood, A. H., Mullen, K. D., Tarter, R. E., Weißenborn, K., & Blei, A. T. (2002) · Hepatology · doi:10.1053/jhep.2002.31250 · Cited by 2,035
Computing topological parameters of biological networks
Assenov, Y., Ramírez, F., Schelhorn, S.-E., Lengauer, T., & Albrecht, M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm554 · Cited by 1,805
The interplay between the intestinal microbiota and the brain
Collins, S. M., Surette, M., & Bercik, P. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2876 · Cited by 1,611 · cited 1×
“We propose that one needs to take a systems biology approach to correlate the complex functional dynamic in the gut ecosystem as a modulator of the gut-brain axis in the human host [14].”
BackgroundRifaximin Treatment in Hepatic Encephalopathy
Bass, N. M., Mullen, K. D., Sanyal, A., Poordad, F., Neff, G., Leevy, C. B., Sigal, S., Sheikh, M. Y., Beavers, K., Frederick, T., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907893 · Cited by 1,300
pcaMethods—a bioconductor package providing PCA methods for incomplete data
Stacklies, W., Redestig, H., Scholz, M., Walther, D., & Selbig, J. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm069 · Cited by 1,156
Flagged first, then by citations
1 of the 46 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 401–430 of 430
Ilie, O., Duta, R., Nita, I.-B., Dobrin, I., Gurzu, I. L., Gîrleanu, I., Huiban, L., Muzica, C. M., Ciobica, A. S., Popescu, R. M., et al. (2023) · Medicina · doi:10.3390/medicina59122143
Minimal hepatic encephalopathy: a bibliometric analysis (1999–2023)
Ju, C., Yang, L., Wang, X., Wang, Y., Tang, S., & Liu, J. (2025) · Current Psychology · doi:10.1007/s12144-025-07495-7
Animal models for complications of cirrhosis
Kaur, S., & Tripathi, D. M. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-99478-1.00007-9
Hepatic encephalopathy in cirrhosis: therapies and developments
Mishra, A. K., & Dhiman, R. K. (2025) · Metabolic Brain Disease · doi:10.1007/s11011-025-01598-7
To be or not to be: the non-antimicrobial properties of common antimicrobials
Narayanan, S., Sneller, L., & Mathur, P. (2025) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkaf150
Rao, A. K., & Rockey, D. C. (2025) · European Journal of Transplantation · doi:10.57603/ejt-1318
Iseli, G. C., Vázquez-Castellanos, J., Coynel, D., Stone, J., Soler, M., Allen, P., Zelaya, F., Derrien, M., Lang, U. E., Debbané, M., et al. (2025) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2025.100567 · Cited by 1
Paradigm shifts in hepatic encephalopathy: Review of recent therapeutic breakthroughs
Ashwin, W., Deva, R., & Girish, C. (2025) · World Journal of Meta-Analysis · doi:10.13105/wjma.v13.i3.108018
Disease Modulating Agents in Cirrhosis
Jahagirdar, V., & Bajaj, J. S. (2025) · Clinics in Liver Disease · doi:10.1016/j.cld.2025.08.008
Casanova‐Ferrer, F., Gallego, J.-J., Fiorillo, A., Urios, A., Ríos, M.-P., León, J. L., Ballester, M.-P., Escudero‐García, D., Kosenko, E. A., Belloch, V., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26667205
Roy, A., Premkumar, M., Sharma, A., Verma, N., Singh, S., De, A., Chopra, M., Taneja, S., Duseja, A., & Dhiman, R. K. (2021) · Research Square · doi:10.21203/rs.3.rs-476864/v1
Mücke, M. M., Rüschenbaum, S., Mayer, A., Mücke, V. T., Schwarzkopf, K. M., Zeuzem, S., Kehrmann, J., Scholtysik, R., & Lange, C. M. (2020) · Figshare · doi:10.6084/m9.figshare.13167381
Jiang, X., Xu, Y., Fagan, A., Patel, B., Zhou, H., & Bajaj, J. S. (2024) · Figshare · doi:10.6084/m9.figshare.26682451
Jiang, X., Xu, Y., Fagan, A., Patel, B., Zhou, H., & Bajaj, J. S. (2024) · Figshare · doi:10.6084/m9.figshare.26682454
Сергеевна, С. Е., Vinnitskaya, E. V., & Parfenov, A. I. (2026) · Terapevticheskii arkhiv · doi:10.26442/00403660.2026.02.203529
Zhu, Y., Gao, W., Cheng, M., Li, X., Cai, K., Chen, L., & Chu, H. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-026-06098-0 · Cited by 1
Agarwal, A., Agrawal, S., Talukdar, D., Kaur, M., Biswas, S., Swaroop, S., Golla, R., Kandiyal, B., Jana, P., Tanwar, S., et al. (2026) · World Journal of Hepatology · doi:10.4254/wjh.v18.i4.116153
Saeki, C., Toyonaga, T., Torisu, Y., Saruta, M., & Tsubota, A. (2026) · Clinical Journal of Gastroenterology · doi:10.1007/s12328-026-02354-9
Hepatic encephalopathy: Part 3, outpatient management
Tranah, T. H., Kronsten, V. T., Frolkis, A. D., Seager, M., Mangini, C., Ntuli, Y., Montagnese, S., Shawcross, D. L., & Tapper, E. B. (2026) · Frontline Gastroenterology · doi:10.1136/flgastro-2026-103734
Cola, S. D., Maiorca, F., Stefanini, L., Sabetta, A., Lombardi, L., D’Amico, T., Lapenna, L., Castellani, V., Romiti, G. F., Cangemi, R., et al. (2026) · Internal and Emergency Medicine · doi:10.1007/s11739-026-04399-7
Oral microbiota dysbiosis and the oral-X axis in chronic diseases
Li, E., Huang, J., Yao, J., Lei, M., & Wu, M. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102274
Editorial: Rifaximin and the Gut–Liver–Brain Axis—Progress and Prudence. Authors' Reply
Inada, H., & Tanaka, Y. (2026) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.70834
The role of ammonia in chronic liver disease
Kerbert, A. J. C., Ballester, M. P., Rose, C. F., & Jalan, R. (2026) · Hepatology Communications · doi:10.1097/hc9.0000000000000993
Minimal Hepatic Encephalopathy: A Narrative Review
Rissardo, J. P., Rashidi, F., Moharam, H., Khalil, I., Bahar, M., Rashidi, M., Ahmed, B., Salem, S., Caprara, A. L. F., Chouthai, A. A., et al. (2026) · Cureus · doi:10.7759/cureus.113978
Li, J., Cao, K., Yang, H., Dong, J., Wang, Q., & Hai, F. (2026) · The Analyst · doi:10.1039/d6an00937a
Microbiome and Diseases: Steatotic Liver Disease
Bergheim, I., & Schneider, K. M. (2026) · Springer eBooks · doi:10.1007/978-3-032-26410-7_17
Tani, J., Tomonari, T., Hirose, A., Moriya, A., Ogawa, C., Tsutsui, A., Morishita, A., Sakamoto, T., Tai, H., Yano, R., et al. (2026) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000003285
Effects of rifaximin on the fecal microbiota of healthy dogs: a pilot study
Harada, H., Tamura, M., Kawabata, M., Sakatani, A., Deguchi, T., Fukuda, A., Usui, M., & Ohta, H. (2026) · Frontiers in Veterinary Science · doi:10.3389/fvets.2026.1761247
Metadata
- Authors
- Bajaj, J. S., Heuman, D. M., Sanyal, A. J., Hylemon, P. B., Sterling, R. K., Stravitz, R. T., Fuchs, M., Ridlon, J. M., Daita, K., Monteith, P., Noble, N. A., White, M. B., Fisher, A., Sikaroodi, M., Rangwala, H., & Gillevet, P. M.
- Affiliations
- Virginia Commonwealth University (US)
- George Mason University (US)
- Corresponding author
- Bajaj, Jasmohan S.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-02
- Volume
- 8
- Issue
- 4
- Pages
- e60042
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3615021
- OpenAlex
- W2138196119
- Cited by
- 430
- References
- 46
- Citations by year
- 2026: 19 · 2025: 27 · 2024: 34 · 2023: 34 · 2022: 25 · 2021: 40 · 2020: 31 · 2019: 37 · 2018: 45 · 2017: 27 · 2016: 31 · 2015: 43 · 2014: 25 · 2013: 9
- FWCI
- 22.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR000058)
- University of California, Davis
- National Institute on Alcohol Abuse and Alcoholism (R01AA020203, RO1AA020203)
- National Institute of Diabetes and Digestive and Kidney Diseases (RO1AA020203, RO1DK087913, R01DK087913)
- National Center for Complementary and Alternative Medicine (RO1AA020203)
- National Center for Advancing Translational Sciences
- National Center for Complementary and Integrative Health (U01AT004428)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- rifaximin, minimal hepatic encephalopathy, liver cirrhosis, gut microbiota, gut-brain axis, endotoxemia, cognitive function, serum metabolomics, urine metabolomics, fatty acids, Veillonellaceae, Enterobacteriaceae, Bacteroidaceae, Porphyromonadaceae
- MeSH terms
- Rifaximin, Cognition, Female, Hepatic Encephalopathy, Humans, Liver Cirrhosis, Male, Middle Aged, Rifamycins, Gastrointestinal Tract, Metagenome, Metabolomics, Metabolome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
