The innovative carbon beads, invented by UCL researchers, reduce bad bacteria and inflammation in animal models, which are linked to liver cirrhosis and other serious health problems.
The study, published in Intestine, found that carbon beads, licensed to UCL spin-out Yaqrit, were effective in restoring gut health and had a positive impact on liver, kidney and brain function in rats and mice. They were also found to be safe for human use.
The next step will be to see if the same benefits can be obtained in humans, which would pave the way for its use to treat diseases related to poor intestinal health.
Worldwide, it is estimated that there are around 100 million people living with liver cirrhosis and 10 million who have cirrhosis plus an additional complication.
Explaining the current clinical challenges, lead author Professor Rajiv Jalan, from the UCL Institute of Liver and Digestive Health, said: “The influence of the gut microbiome on health is only beginning to be fully appreciated. When the balance of the gut microbiome is disrupted, microbiome, “Bad” bacteria can proliferate and compete with “good” bacteria that keep the gut healthy.
“One of the ways they do this is by excreting endotoxins, toxic metabolites and cytokines that transform the intestinal environment to make it more favorable to them and hostile to good bacteria. These substances, particularly endotoxins, can trigger intestinal inflammation and increase the leakage of the intestinal wall, causing damage to other organs such as the liver, kidneys and brain.
“In cirrhosis, a disease characterized by scarring of the liver, it is known that inflammation caused by endotoxins can exacerbate liver damage. Part of the standard treatment for cirrhosis is antibiotics aimed at controlling bad bacteria, but this comes with the risk of antibiotic resistance and is only used in advanced-stage disease.
To overcome this, UCL scientists, in collaboration with Yaqrit, developed small oral carbon beads, which have a special microscopic physical structure designed to adsorb large and small molecules in the intestine.
In the study, UCL researchers tested the effectiveness of carbon beads, known under the product name CARBALIVE, in restoring gut health and assessed the impact on liver, kidney and brain function in rats and mice.
They found that when ingested every day for several weeks, the beads were effective in preventing the progression of liver scarring and injury in animals with cirrhosis, and reduced mortality in animals with acute-on-chronic liver failure (ACLF).
The beads were also tested on 28 patients with cirrhosis and were shown to be safe with negligible side effects. If the same benefits seen in animal models occur in humans, the beads could be an important new tool to help combat liver disease.
Michal Kowalski, vice president and CARBALIVE product leader at Yaqrit, said: “These novel engineered carbon beads, which are swallowed and passed through the body unchanged, are smaller than a grain of salt. They work by absorbing endotoxins and other metabolites produced by “bad” bacteria in the gut, creating a better environment for good bacteria to flourish and helping to restore the health of the microbiome. This prevents these toxins from leaking into other areas of the body and causing damage, as occurs in cirrhosis. .
“The results in animal models are very positive, with reduced intestinal permeability, liver damage, as well as brain and kidney dysfunction.”
The results open the door to new trials to test the effectiveness of carbon beads in humans, one of which will begin soon. If beads are shown to be effective in stopping or slowing the progression of liver damage, they could be an invaluable tool in treating liver disease and possibly other conditions associated with poor microbiome health.
Professor Jalan, Professor of Hepatology at UCL and Consultant at the Royal Free Hospital, added: “I very much hope that the positive impact of these carbon beads in animal models will be seen in humans, which is exciting not only for treatment. of liver disease, but potentially any health condition caused or exacerbated by a gut microbiome not working as it should. This could include conditions such as irritable bowel syndrome, for example, which is on the rise in many countries.
“The study is another milestone in a journey that began at UCL and has evolved into our company Yaqrit, thanks to funding from the European Union’s Horizon 2020 research and innovation programme. This has allowed us to build a factory to manufacture accounts. and allowed for research into their potential uses. I am optimistic that this journey will end with the approval of these pearls to help treat liver diseases and other conditions in the coming years.”
This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 634579.