Availability of intestinal microbial lysine for whole body lysine homeostasis in human subjects

We have investigated whether there is a net contribution of lysine synthesi zed de novo by the gastrointestinal microflora to lysine homeostasis in six adults. On two separate occasions an adequate diet was given for a total o f 11 days, and a 24-h (12-h fast, 12-h fed) tracer protocol was performed o n the last day, in which lysine turnover, oxidation, and splanchnic uptake were measured on the basis of intravenous and oral administration of L-[1-C -13]lysine and L-[6,6-H-2(2)]lysine, respectively. [N-15(2)]urea or (NH4Cl) -N-15 was ingested daily over the last 6 days to label microbial protein. I n addition, seven ileostomates were studied with (NH4Cl)-N-15. [N-15]lysine enrichment in fecal and ileal microbial protein, as precursor for microbia l lysine absorption, and in plasma free lysine was measured by gas chromato graphy-combustion-isotope ratio mass spectrometry. Differences in plasma [C -13]- and [H-2(2)]lysine enrichments during the 12-h fed period were observ ed between the two N-15 tracer studies, although the reason is unclear, and possibly unrelated to the tracer form per se. In the normal adults, after (NH4Cl)-N-15 and [N-15(2)]urea intake, respectively, lysine derived from fe cal microbial protein accounted for 5 and 9% of the appearance rate of plas ma lysine. With ileal microbial lysine enrichment, the contribution of micr obial lysine to plasma lysine appearance was 44%. This amounts to a gross m icrobial lysine contribution to whole body plasma lysine turnover of betwee n 11 and 130 mg.kg(-1).day(-1), depending on the [15N]lysine precursor used . However, insofar as microbial amino acid synthesis is accompanied by micr obial breakdown of endogenous amino acids or their oxidation by intestinal tissues, this may not reflect a net increase in lysine absorption. Thus we cannot reliably estimate the quantitative contribution of microbial lysine to host lysine homeostasis with the present paradigm. However, the results confirm the significant presence of lysine of microbial origin in the plasm a free lysine pool.