Phage combination therapy for chronic intestinal inflammation
A new form of so-called combination phage therapy is able to specifically combat gut bacteria associated with chronic inflammatory bowel disease without negatively affecting beneficial gut bacteria.
A new study involving experts from the Weizmann Institute of Science has looked at how phages (bacteria-specialized viruses) can be used to treat diseases related to gut flora. The results were published in the specialist journal Cell.
Bacteria and inflammatory bowel disease
The researchers analyzed the composition of the gut microbiota of 537 people with inflammatory bowel disease (IBD). They found that people with inflammatory bowel disease tend to accumulate a group of strains of Klebsiella pneumoniae (dangerous hospital germs) in their intestines. This was especially true for those affected who experienced a flare-up of the disease.
When the Klebsiella pneumoniae strains were transplanted into mice, the animals developed severe intestinal inflammation and tissue damage, the researchers report. This indicates that the bacterium may contribute to the intensification of inflammatory bowel disease.
In search of effective phages
Next, the experts examined and isolated thousands of bacteriophages from environmental samples. Bacteriophages are viruses that attack and infect bacteria. The team identified around 40 phages that appeared to be effective against strains of Klebsiella pneumoniae – including strains that had already developed resistance to the phages.
Such resistance is "the biggest problem when using phage therapies," says study author Eran Elinav in a press release. If you apply a single phage to a bacterium, the bacterium will probably develop resistance mechanisms very quickly.
Combined phage study
A combination of two phages was therefore tested representatively in a clinical study with 18 participants. The phages were found to survive in high concentrations and remain active throughout the gastrointestinal tract when ingested with an antacid (a substance used to neutralize stomach acid). According to the researchers, there was also no alteration of the surrounding microbiota.
Phages have proven to be a potential treatment cocktail against strains of Klebsiella pneumoniae that cause inflammatory bowel disease. In these phage combinations, each of the phages uses a different receptor to enter the bacteria, allowing them to be killed by different mechanisms, the researchers explain.
The advantage is that even mutated bacteria that have had one of their receptors become resistant still have treatment options. So an effective cocktail can prevent the formation and spread of phage-resistant bacteria, according to study author Eran Elinav of the Weizmann Institute of Science.
Most effective five-phage combination
In further investigations in the test tube and also in mouse models with inflammatory bowel disease, it became clear that a special combination of five different phages most effectively combat strains of Klebsiella pneumoniae, so that inflammation and tissue damage are weakened, the researchers report.
According to Elinav, the current study demonstrated for the first time that an orally administered phage combination therapy can be used against a pathogenic intestinal resident while simultaneously addressing the problem of phage resistance and neutralizing a non-communicable disease. .
Generalized chronic inflammatory bowel disease
These non-communicable inflammatory bowel diseases affect millions of people worldwide. Its causes remain largely unclear, although previous research has shown that certain bacteria in the gut are linked to the condition.
Attempts have already been made to treat inflammatory bowel disease using antibiotics. However, the treatments turned out not to be specific or effective enough, the researchers report.
Because antibiotics kill both beneficial and disease-causing gut bacteria. This can lead to unwanted side effects. There is also a risk of developing antibiotic resistant bacteria.
Phages as a precision weapon against bacterial strains
However, the research team has now succeeded in using phages as a sort of precision weapon to suppress a group of so-called commensal bacterial strains that contribute to inflammatory bowel disease.
Furthermore, the researchers hope that the combined phage therapy can be developed in the future and also used against bacteria implicated in obesity, diabetes, cancer and neurodegenerative diseases, for example. (as)
Author and source information
Show nowThis text corresponds to the specifications of the specialized medical literature, medical guidelines and current studies and has been verified by health professionals.
Sources:
Sara Federici, Sharon Kredo-Russo, Rafael Valdés-Mas, Denise Kviatcovsky, Eyal Weinstock, et al. : targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for the treatment of gut inflammation; in: Cell (published 08/04/2022), CellCell Press: Phage combination therapy can precisely target IBD-linked gut bacteria without harming helpful microbes (published 08/04/2022), Cell PressImportant note:
This article contains general advice only and should not be used for self-diagnosis or treatment. It cannot substitute a visit to the doctor.
