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Study identifies mechanism by which intestinal enzyme maintains microbial balance
Date:5/9/2014

ng exactly how the enzyme helps maintain the microbial population an open question that the current study was designed to investigate.

A series of experiments first confirmed that mice lacking intestinal IAP had significant reductions in populations of several important bacterial species. Hypothesizing that IAP may act by blocking a growth-inhibiting activity of one of its target molecules, the researchers tested how well bacteria in stool samples would grow in the presence of four known IAP targets. Among the tested targets, only ATP significantly reduced bacterial growth; and ATP's inhibitory effects were reversed by application of IAP. Best known as the primary energy supply within cells, ATP also acts as a signaling molecule both inside and outside of cells, and this study is the first to identify such an activity for ATP within the gastrointestinal system.

Experiments in living mice revealed that IAP knockout animals had 10 times the normal level of ATP within their intestines and that fasting animals, in which IAP levels would be expected to drop, also had elevated intestinal ATP. Adding ATP to the intestines of mice in which IAP activity had been inhibited reduced levels of beneficial E.coli bacteria in the animals' digestive systems. Altogether the results show that ATP inhibits the growth of intestinal bacteria in mice and that IAP's growth-promoting effects result from the enzyme's inactivation of ATP and possibly of related molecules.

"Now we need to find out whether IAP also promotes the growth of beneficial intestinal bacteria in humans," says Hodin, who is a professor of Surgery at Harvard Medical School. "If it does, IAP-based therapies could offer a simple and safe approach to treating the millions of patients who suffer serious health problems caused by disruptions to intestinal microbial balance."


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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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