Segmental differences in short-chain fatty acid transport in rabbit colon: Effect of pH and Na

Abstract

Short-chain fatty acids (SCFAs) are the predominant luminal anion in the mammalian colon. Although they are rapidly absorbed in vivo, little is known about the mechanisms of transepithelial transport in vitro. Previous studies have suggested that SCFA transport may be linked to Na absorption or an anion exchange mechanism. We compared the transport of propionate under short-circuit conditions in rabbit proximal and distal colon to determine whether there were segmental differences, how SCFAs may be linked to either Na absorption or anion transport, and whether SCFAs, as weak electrolytes, may be affected by transepithelial pH gradients. In distal colon, propionate transport was not significantly altered by stimulation of electrogenic Na absorption, epinephrine or Cl removal. However, a modest transepithelial pH gradient (luminal 6.8/serosal 7.4) stimulated propionate absorption. In proximal colon, propionate transport was significantly altered by maneuvers that either stimulated (lowered [Na] in the bathing media) or inhibited (theophylline) apical Na-H exchange. Neither Cl removal, nor the anion exchange inhibitor DIDS, nor a transepithelial bicarbonate gradient, altered propionate transport. A transepithelial pH gradient inhibited propionate secretion, but not in a manner entirely consistent with the effect of pH on the distribution of a weak electrolyte. These results suggest that there is significant segmental heterogeneity in colonic SCFA transport; that transepithelial propionate fluxes are altered by changes in pH or electroneutral Na absorption (Na-H exchange), but not by chloride removal, bicarbonate gradients or electrogenic Na absorption. Regulation of SCFA transport may be an important factor in the physiology of colonic fluid balance.

Extracellular pH regulation in microdomains of colonic crypts: effects of short-chain fatty acids.

“…Mechanisms of transepithelial SCFA fluxes are being debated but are likely to include a combination of nonionic diffusion of these weak acids (9,19,(26)(27)(28) and the activity of defined colonocyte monocarboxylate transporters (e.g., carrier-mediated SCFA-/HCO3-exchange and/or SCFA-/H+ cotransport) (29,32). Simple models of transcellular SCFA fluxes via any of these transporters can explain our observations.…”

“…Assuming constant transepithelial flux of acid/base equivalents, results can be explained by colonic crypts contributing 33 mM HI/pH unit of extracellular buffering capacity to the lumen. This upper estimate will be lowered if SCFA fluxes are inhibited by luminal alkalinization (6,26,27) or if perfusate buffers do not attain full concentration within the lumen.…”

“…. ; addition, regulation of extracellular pH will affect the pH-sensitive fraction of transepithelial SCFA absorption and may have confounded tissue experiments testing the pH sensitivity of SCFA transport (4,6,27,37). The transepithelial pH gradient established by SCFAs is also a driving force for titration of other weak acids and bases across the epithelium, potentially explaining how SCFAs stimulate colonic bicarbonate secretion (38) and ammonia absorption (39).…”

Butyrate utilization by the colonic mucosa in inflammatory bowel diseases

“…In mammals, butyrate transport was first characterized using colon segments of guinea pig, 28 rat, 29 and rabbit 30 mounted in Ussing chambers. In these experiments the main way of SCFA absorption across the intestinal mucosa was found to be the nonionic diffusion of protonated SCFAs.…”

Are Right- and Left-Sided Colon Neoplasms Distinct Tumors?

“…In the proximal colon, ouabain and lidocaine inhibit the absorption of Evans blue, but increase the dye uptake in the distal colon [28]. Short-chain fatty acids are ab sorbed differently in the right and in the left colon [29], Propionate absorption in the prox imal colon is linked to a sodium-hydrogen exchange mechanism. In the distal colon, pro pionate behaves as a weak electrolyte and moves from a more acidic to a less acidic environment.…”