Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with rifaximin in cirrhosis: implications for the gut-liver-brain axis
Open accessAbstract
Unlabelled Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE.Hypothesis Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks.Methods Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. RESULTS were compared before/after rifaximin.Results 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92% medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.
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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.
“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 [418]
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- Authors
- Ahluwalia, V., Wade, J. B., Heuman, D. M., Hammeke, T. A., Sanyal, A. J., Sterling, R. K., Stravitz, R. T., Luketic, V., Siddiqui, M. S., Puri, P., Fuchs, M., Lennon, M. J., Kraft, K. A., Gilles, H., White, M. B., Noble, N. A., & Bajaj, J. S.
- Affiliations
- Virginia Commonwealth University (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Bajaj, Jasmohan S.
- ORCID
- Venue
- Metabolic Brain Disease
- Published
- 2014-03-04
- Volume
- 29
- Issue
- 4
- Pages
- 1017-1025
- ISSN
- 0885-7490 (ISSN-L)
- 1573-7365
- PMC
- PMC4155029
- OpenAlex
- W2025612159
- Cited by
- 92
- References
- 40
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 11 · 2023: 6 · 2022: 9 · 2021: 9 · 2020: 2 · 2019: 7 · 2018: 14 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 4
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Metabolic Brain Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA020203)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087913)
- National Center for Complementary and Integrative Health (U01AT004428)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- rifaximin, minimal hepatic encephalopathy, liver cirrhosis, gut-liver-brain axis, endotoxemia, working memory, inhibitory control, functional connectivity, n-back task, subcortical activation, fractional anisotropy, brain metabolites, cognitive impairment
- MeSH terms
- Rifaximin, Anti-Bacterial Agents, Brain, Brain Chemistry, Cognition Disorders, Female, Hepatic Encephalopathy, Humans, Inhibition, Psychological, Intestines, Liver, Liver Cirrhosis, Magnetic Resonance Imaging, Male, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Magnetic Resonance Spectroscopy, Rifamycins, Bacterial Translocation, Diffusion Tensor Imaging, Functional Neuroimaging, Connectome, Microbiota, Multimodal Imaging
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