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Production of Diacylglycerol, an Activator of Protein Kinase C, by Human Intestinal Microflora¹

Departments of Surgery [M. M., J. G. G., P. L.] and Medicine [M. M., J. G. G., P. L., I. B. W.], and the Comprehensive Cancer Center and Institute of Cancer Research [I. B. W.], Columbia-Presbyterian Medical Center of Columbia University, New York, New York 10032, and the Yakult Institute for Microbiological Research, 1796 Yaho, Kunitachi, 186 Tokyo, Japan [M. M.]

Although dietary lipids have been implicated in colon cancer causation, the underlying mechanisms are not known. This paper indicates that when bacteria obtained from normal human feces are incubated with ¹⁴C-labeled phosphatidylcholine there is appreciable production of diacylglycerol (DAG), monoacylglycerol, and free fatty acid. Curiously, the production of DAG and monoacylglycerol, but not fatty acid, is strictly dependent on addition of certain bile acids to the incubation system. Among the bile acids tested deoxycholic acid is the most active. Assays of fecal specimens from 10 normal individuals demonstrate a 27-fold interindividual variation in the production of DAG in the in vitro assay system, and also in the absolute levels of DAG present in the same fecal samples. On the other hand, both parameters of DAG are quite constant in repeated fecal samples obtained from the same individual over a period of about 4 months. DAG is a normal physiological activator of protein kinase C, an enzyme that plays a key role in growth control and tumor promotion. We speculate, therefore, that DAG produced by the intestinal microflora might stimulate growth of colonic epithelial cells. Thus an interaction between dietary lipids, bile acids, and specific bacteria in the intestinal lumen could contribute to the risk of colon cancer development in humans.

¹ This research was supported by an award to Columbia University from the Yakult Honsha Company, Tokyo (to P. L.) and from the Aaron Diamond Foundation, New York, New York (to I. B. W.).

² To whom requests for reprints should be addressed, at Institute of Cancer Research, College of Physicians & Surgeons of Columbia University, 701 W. 168 St., New York, NY 10032.

Received 12/13/89. Revised 3/19/90.

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