Bacterial memory of gut inflammation

Stable engineered bacteria that retain long-term memory of gut inflammation could be used as living diagnostics for chronic intestinal diseases and other conditions, according to new research.

The microbiome, or the collections of microorganisms present in the body, is known to affect human health and disease and researchers are thinking about new ways to use them as next-generation diagnostics and therapeutics. Today bacteria from the normal microbiome are already being used in their modified or attenuated form in probiotics and cancer therapy. Scientists exploit the microorganisms' natural ability to sense and respond to environmental- and disease-related stimuli and the ease of engineering new functions into them. This is particularly beneficial in chronic inflammatory diseases like inflammatory bowel disease (IBD) that remain difficult to monitor non-invasively. However, there are several challenges associated with developing living diagnostics and therapeutics including generating robust sensors that do not crash and are capable of long-term monitoring of biomolecules.

In order to use bacteria of the microbiome as biomarker sensors, their genome needs to be modified with synthetic genetic circuits, or a set of genes that work together to achieve a sensory or response function. Some of these genetic alterations may weaken or break normal signaling circuits and be toxic to these bacteria. Even in cases where the probiotic microbes tolerate the changes, the engineered cells can have growth delays and be outcompeted by other components of the microbiome. As a result, probiotic bacteria and engineered therapeutic microbes are rapidly cleared from the body, which makes them inadequate for long period monitoring and modulation of the organism's tissue environment.

A team at the Wyss Institute of Biologically Inspired Engineering led by Pamela Silver, Ph.D., designed a powerful bacterial sensor with a stable gene circuit in a colonizing bacterial strain that can record gut inflammation for six months in mice. This study offers a solution to previous challenges associated with living diagnostics and may bring them closer to use in human patients. The findings are reported in Nature Biotechnology.

See:

David T Riglar, Tobias W Giessen, Michael Baym, S Jordan Kerns, Matthew J Niederhuber, Roderick T Bronson, Jonathan W Kotula, Georg K Gerber, Jeffrey C Way, Pamela A Silver. Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Nature Biotechnology, 2017; DOI: 10.1038/nbt.3879

Posted by Dr. Tim Sandle