Related Experiment Video
Updated: Jul 5, 2025
Author Spotlight: Methodologies and Advancements of Chronic Pain Management Research
Published on: January 5, 2024
Improved cognition after rifaximin treatment is associated with changes in intra- and inter-brain network functional
Franc Casanova-Ferrer1, Juan-José Gallego1, Alessandra Fiorillo1
1Fundacion de Investigación Hospital Clinico Universitario de Valencia-INCLIVA, Valencia, Spain.
Background:
Rifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well.
Methods:
Twenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed.
Results:
After rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers.
Conclusions:
There was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.
Insights
Rifaximin treatment improved brain network communication in minimal hepatic encephalopathy (MHE) patients, enhancing cognitive function. Responders showed better brain connectivity and reduced inflammation compared to non-responders.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- Minimal hepatic encephalopathy (MHE) is associated with cognitive deficits and inflammation.
- Rifaximin, a gut-acting antibiotic, shows variable efficacy in MHE patients.
- Understanding brain network changes is crucial for optimizing MHE treatment.
Purpose of the Study:
- To investigate brain activity and network connectivity changes after rifaximin treatment in MHE patients.
- To differentiate treatment effects between patients who respond and those who do not.
- To correlate neuroimaging findings with cognitive and inflammatory markers.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was used to assess resting-state brain activity in MHE patients before and after rifaximin treatment.
- Psychometric tests and inflammatory cytokine levels were measured to assess cognitive function and inflammation.
- Patients were categorized into responders and non-responders based on cognitive improvement.
Main Results:
- Rifaximin treatment globally affected sensorimotor and fronto-parietal networks.
- Responder patients exhibited increased thalamic network connectivity and reduced plasma inflammatory cytokines.
- Pre-treatment connectivity differences in the basal ganglia network distinguished responders from non-responders.
Conclusions:
- Rifaximin treatment enhances communication and functional independence between executive, motor, and attention-related brain areas.
- Improved inflammatory status in MHE patients correlates with observed brain function changes and cognitive enhancement.
- Individualized treatment approaches may be beneficial, considering baseline brain connectivity and inflammatory markers.
