Health
Phage combinations may promote gut health by precisely targeting IBD-associated bugs
Human gut biodiversity is important. In addition to bacteria (microbiome) and fungi (mycobiome), the gut contains hundreds of thousands of viruses called bacteriophages, which can infect bacteria.
New data published in the journal cell We now demonstrate the potential of using phages to modulate the gut microbiota to improve health.
A new study, led by scientists at the Weizmann Institute of Science in Israel, analyzed the composition of the gut microbiota of 537 IBD patients and found that these people: Klebsiella pneumoniae(Kp). When they transplanted Kp into mice, the animals developed severe intestinal inflammation and tissue damage, suggesting that these Kp strains may contribute to the exacerbation of IBD.
The researchers then identified 40 phages that appeared to be effective against Kp strains that contribute to IBD, narrowing them down to five phage combinations. Each phage uses different receptors to enter bacteria and kill them by different mechanisms.
Even if the bacterium mutates and one of its receptors becomes resistant, there will be backups, say the Weizmann Institute of Science’s Department of Systems Immunology and the German National Cancer Center’s (DKFZ) Department of Microbiome and Cancer. Director Eran Elinav said. Corresponding author of the study. He added that effective cocktail design can prevent the formation and spread of phage-resistant bacteria.
“To the best of our knowledge, we are the ones who have addressed the major problem of phage resistance and used orally administered phage combination therapy against disease-causing intestinal commensals while treating non-communicable diseases. is the first time.” Dr. Elinahu said.
efficacyna
Studies in test tubes and laboratory mice have shown that this phage cocktail can suppress Kp and reduce the associated inflammation and tissue damage.
“This proof-of-concept study utilizes phages as precision weapons to suppress a group of commensal strains that contribute to IBD.” Dr. Elinahu said.
“However, our vision is that this new modality will be developed and used against many other IBD-related bugs, as well as commensals implicated in other diseases, including obesity, diabetes, cancer, neurodegenerative diseases, etc. It is possible that it could be applied tona
Expert: ‘Phages have great potential in managing intestinal disorders and health’na
Dr. Mark Miller of Kaiviti Consulting, LLC commented independently on the study, speaking to NutraIngredients-USA about the comprehensive, multi-layered study. “Phages underscore the great potential in managing intestinal disorders and health. na
“This is an impressive collaboration that provides an excellent ‘proof of principle’ that phages play a role in alleviating pathology caused by antibiotic-resistant bacteria. Klebsiella pneumoniae. na
Dr. Miller added that, importantly, use of these phages did not cause dysbiosis. “Microbiome diversity was intact, except for Klebsiella, a target whose levels were greatly reduced by phage therapy.” he pointed out.
“This study is important for several reasons.”Dr. Miller added. “First, our predictive model clearly shows that phage therapy is effective in counteracting the devastating effects of antibiotic-resistant bacteria. They do not cause destruction of the good bacteria present in our microbiome and do not target host cells.”na
Dr. Miller said phages have great potential in managing diseases caused by antibiotic-resistant bacteria. “We’ve basically run out of therapeutic resources. na
“This paper highlights the potential of phages. It highlights great hopes for a state of great public concern: the inherent existence of antibiotic-resistant bacteria.”na
move to humansna
Dr. Elinav and his colleagues also conducted a Phase I clinical trial in 18 healthy volunteers. This trial showed that the phage could survive at high levels and remain active throughout the gastrointestinal tract when taken with antacids, without affecting the surrounding microbiota.
“Phage therapy showed an excellent safety profile with no adverse events.” Dr. Miller commented. “This is very encouraging.”na
The research team now plans to test the five-phage cocktail in a phase II trial in IBD patients who carry the disease-contributing Kp strain.
In addition, Elinav and his team are said to be working on identifying bacteria associated with other diseases and developing effective phage combination therapies against them.
“What we envision is a precision medicine pipeline.” Elinahu said. “It can be used to characterize pathogenic bacteria in people suffering from gut microbiota-related diseases and apply personalized phage therapy to suppress the bacteria.”na
fundraisingna
This project was financially supported by Takeda, Janssen, Abbott, Pfizer, Abbvie, Neopharm, Corundum Innovation Ltd, Mycolivia and Nestlé.
sauce: cellna
Published online prior to printing. 10.1016/j.cell.2022.07.003na
“Targeted inhibition of human IBD-associated gut microbiota symbiosis by phage consortia for the treatment of intestinal inflammation”na
Author: S. Federici et al.
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