Otto Kretschmer
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- Joined
- Feb 12, 2024
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- https://www.medicalnewstoday.com/articles/carbon-beads-may-help-reduce-liver-disease-restore-gut-health
- https://gut.bmj.com/content/early/2024/04/24/gutjnl-2023-330699
The study, published in Gut, indicates that these beads, now licensed to UCL-spinout Yaqrit, successfully improved gut, liver, kidney, and brain health in rats and mice, and were deemed safe for human application.
- Innovative carbon beads developed by researchers at UCL could one day become a new method of treating diseases linked to poor gut health, such as liver cirrhosis, which affects millions worldwide.
- New research has revealed that these beads, capable of absorbing harmful bacteria and toxins, significantly improved gut, liver, kidney, and brain health in animal models and showed potential for human application.
- Further research is needed, however, these beads may represent a promising step forward in addressing the issues associated with gut microbiota imbalances.
Abstract
Objective Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis.
Design Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed.
Results Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial.
Conclusions This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation.
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