Phage combination therapy that can precisely target IBD-related gut bacteria without harming helpful

For the first time, scientists have designed a phage combination therapy that can precisely target and suppress gut bacteria associated with inflammatory bowel diseases (IBD).

Elinav et. al compared the gut microbiota compositions of 537 IBD patients to healthy controls enrolled in cohort studies in France, Israel, the U.S., and Germany. The team found IBD patients, despite their differences in geography, ethnicity, and diet, tend to have a group of Klebsiella pneumonia (Kp) strains enriched in their gut, especially in those who are experiencing disease flare-ups. When transplanting the Kp into mice, the team found that mice developed severe intestinal inflammation and tissue damage, suggesting that these Kp strains may contribute to the worsening of IBD.

Next, Elinav and his team scanned and isolated thousands of bacteriophages from environmental samples. Bacteriophages are viruses that can target and infect bacteria. They identified some 40 phages that appear to be effective against the IBD-contributing Kp strains, including strains that have already developed phage resistance.

The team tested the phages in various groups as a potential cocktail treatment against IBD-contributing Kp strains. In these phage combinations, each of the phages uses a different receptor to enter bacteria and kills them through different mechanisms.

Elinav and his team discovered the most effective phage combination, which contains five phages, in suppressing the Kp strains in the test tube, as well as in mice IBD models, where the phage cocktail attenuated inflammation and tissue damage.

The team further tested two representative phages from this cocktail in phase I clinical trial that involves 18 healthy volunteers. The experiment showed that the phages can survive at high levels and remain active throughout the gastrointestinal tract when taken with antacids while not impacting the surrounding microbiota. Participants had no severe treatment-related adverse events. The team plans to further test the 5-phage cocktail in a subsequent phase II trial encompassing IBD patients that harbor the disease-contributing Kp strains. In addition, Elinav and his team are working to identify bacteria associated with other diseases and to develop effective phage combination therapies against them.

Ref:

Eran Elinav et. al, Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation, Cell, 4-Aug-2022, 10.1016/j.cell.2022.07.003