MICROBIOMES

Phage therapy suppresses gut inflammation in IBD

The gut microbiota is known to contribute to the pathology of inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis. But treatments that tackle the entire microbiome such as wide-spectrum antibiotics and fecal microbiota transplants have yielded inconsistent results and have been associated with adverse effects. A study reported in Celluses bacteriophage consortia to target and eliminate specific gut bacteria as a treatment for IBD.

The researchers analyzed stool samples from four geographically independent IBD cohorts (n = 537) using shotgun metagenomics and differential abundance analysis. They found five bacterial species significantly enriched in patients with IBD as compared with controls (adjusted P < 0.05). Among these was Klebsiella pneumoniae, which on further analysis yielded an ‘IBD-associated,’ or Kp2, clade.

From the stool of patients with IBD, the authors isolated Kp2 bacteria, which they transferred to germ-free mice, providing a mouse model for IBD. They then tested different phages for their ability to suppress Kp2 strains. “We isolated thousands of phages from samples collected from the sewer, dental waste and microbiome samples, grew and characterized them, and engaged in prolonged iterative mix-and-match experiments,” say Sara Federici and Eran Elinav, first author and corresponding author of the study, respectively. The resulting five-phage cocktail successfully ameliorated inflammation in the mouse IBD model.

Finally, two phages were selected for testing in healthy volunteers in a first-in-human, phase 1, randomized, single-blinded, placebo-controlled clinical trial (NCT04737876). The phages were well-tolerated, with mild adverse effects.

**Kotsiliti, E. Phage therapy suppresses gut inflammation in IBD. Nat Biotechnol 40, 1327 (2022). https://doi.org/10.1038/s41587-022-01477-x