A surprising precision weapon against Crohn’s and ulcerative colitis

A team of Weizmann Institute of Science researchers in the lab of Prof. Eran Elinav, from the Department of Systems Immunology, has demonstrated that a type of virus known as a phage has the potential to serve as a precision weapon against inflammation-causing gut bacteria.

Attempts to enlist phage–which are found wherever there are bacteria, including the human gut–date back over 100 years, but were abandoned in the advent of antibiotics. But now researchers are giving this cast-off microbe a second chance to fight disease.

Postdoctoral fellows Drs. Sara Federici, Rafael Valdés Mas and Denise Kviatcovsky conducted the study in collaboration with Dr. Sharon Kredo-Russo and other researchers from BiomX Inc., a startup advancing novel phage therapies based on Weizmann Institute research, and Prof. Rotem Sorek of Weizmann’s Department of Molecular Genetics.

The researchers identified several strains of the Klebsiella pneumoniae bacterium as likely contributors to intestinal inflammation and found that mice implanted with these bacteria suffered worse inflammation and intestinal damage.

The scientists then looked for an ideal phage combination that would “disarm” bacteria. A cocktail of 5 phages was selected.

In a laboratory system simulating the human gut, two representative phages from the cocktail were shown to be stable when used together with antacids. In a follow-up Phase I clinical trial with 18 healthy volunteers, the phages were found to be well-tolerated. Importantly, the phages persisted and even multiplied in the human intestines over time, while causing no unwanted changes in the rest of the gut microbes.

If proved safe and effective in larger clinical trials, the phage cocktail could lead to phage therapies for other disorders influenced by gut microbes, including obesity, diabetes, neurodegenerative disease and possibly even cancer.

Prof. Eran Elinav’s research is supported by the Adelis Foundation; the Norman E. Alexander Family M Foundation; Miel de Botton; the Leona M. and Harry B. Helmsley Charitable Trust; the Morris Kahn Institute for Human Immunology; the Jeanne and Joseph Nissim Center for Life Sciences Research; the Rising Tide Foundation; the Mike and Valeria Rosenbloom Foundation; the Sagol Institute for Longevity Research; the Sagol Weizmann-MIT Bridge Program; the Swiss Society Institute for Cancer Prevention Research; the Vainboim Family. The Vera Rosenberg Schwartz Research Fellow Chair supports a staff scientist in the Elinav lab. Prof. Elinav is Head of the Belle S. and Irving E. Meller Center for the Biology of Aging, and the incumbent of the Sir Marc and Lady Tania Feldmann Professorial Chair of Immunology.