Ученые разработали инструмент для точного включения и выключения генов кишечных бактерий

Weill Cornell Medicine researchers have developed molecular tools that can switch specific genes in common intestinal bacteria on or off, a step they say could clarify how the microbes affect health and disease. The work, published Aug. 25 in Nature Biotechnology, focuses on Clostridia, a broad class that can make up about half of the bacteria in a healthy person’s gut. Some species produce potentially beneficial metabolites, while others are associated with conditions ranging from intestinal inflammation to diabetes and cancer. A controllable genetic switch The team tested 67 gene-regulating DNA sequences from one Clostridia strain and identified a strong promoter, then connected it to a switch controlled by a chemical inducer. Researchers used the system to regulate selected bacterial metabolic genes both in culture and in mice. As test cases, they changed production of trimethylamine and deoxycholic acid. Prior research has linked those compounds to a mix of harmful and potentially useful effects, including blood-clot risk, cancer immune response and the effectiveness of some immunotherapies. The team also developed a CRISPR-based system that can disable genes in Clostridia collected from clinical samples. That could help researchers test which microbial genes or metabolites affect intestinal immunity or disease. Possible path to engineered treatments Study leader Chun-Jun “C.J.” Guo said the tools could eventually support engineered living therapies that deliver beneficial metabolites in controlled amounts. The research does not establish a treatment and was conducted in laboratory systems and mice. The work received support from several National Institutes of Health institutes, the American Gastroenterological Association, the W.M. Keck Foundation and other funders.