Regulation of short-chain fatty acid transport and metabolism across the rumen epithelium

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Short-chain fatty acids (SCFA), a product of anaerobic fermentation in the rumen, are the primary energy source for ruminants. Increasing diet fermentability increases SCFA production and animal productivity(18), with SCFA absorption stabilizing the ruminal environment(6). However, the regulatory factors for SCFA absorption across the rumen epithelium (RE) are not well understood. Expression of free fatty acid receptors (FFA) 2 and 3(39) and toll-like receptors (TLR) 2 and 4(22) have been reported in the rumen. In the colon, FFA2 and FFA3 have been localized in enteroendocrine cells(25). Stimulation of FFA2 and FFA3 by SCFA, stimulates neuroendocrine signalling(37) thereby modulating SCFA absorption. The RE does not contain enteroendocrine cells and therefore, studies to determine localization in the RE are needed. TLR2 and 4 are expressed in the RE(22) and stimulation of TLR has been reported to decrease free fatty acid uptake and reduce lipid metabolism in adipocytes(11); it is not known if similar results occur in the RE. The hypothesis is that luminal sensing mechanisms regulate RE SCFA absorption and metabolism. The objectives are to; 1) characterize potential luminal-sensing mechanisms involved in the regulation of SCFA absorption and metabolism by the RE, 2) elucidate the regulatory role of luminal-sensing mechanisms on the absorption and metabolism of SCFA by the RE, and 3) evaluate whether dietary treatments can induce changes in the expression and activity of luminal-sensing mechanisms. To address these objectives, two PhD students will be recruited to conduct a series of studies with one student focusing on pattern recognition receptors (PRR) such as TLR and the other focusing on luminal nutrient receptors (LNR). The studies will determine the localization and expression of PRR and LNR throughout the ruminant gastrointestinal tract using PCR and immunohistochemistry. In vitro studies with isolated RE cells will be used to evaluate the role of agonists and antagonists of the PRR and LNR on SCFA metabolism and Ussing chamber experiments will be conducted to examine whether PRR and LNR regulate SCFA absorption. Finally, in vivo studies will be conducted to evaluate whether (and how) PRR and LNR regulate blood flow and splanchnic metabolism of SCFA. This research program will provide novel information on regulatory mechanisms for the absorptive metabolism of SCFA and may lead to the development of novel compounds to improve the efficiency, and health of ruminants by increasing SCFA absorption.**