Nonionic diffusion of short-chain fatty acids across rat colon

Abstract

Short-chain fatty acid (SCFA) transport across the colon may occur by nonionic diffusion and/or via apical membrane SCFA−/[Formula: see text]exchange. To examine the relative importance of these processes, stripped segments of rat ( Ratus ratus) proximal and distal colon were studied in Ussing chambers, and the unidirectional fluxes of radiolabeled SCFA butyrate, propionate, or weakly metabolized isobutyrate were measured. In N-2-hydroxyethylpiperazine- N′-2-ethanesulfonic acid (HEPES) or 1 or 5 mM [Formula: see text] Ringer, decreases in mucosal pH stimulated mucosal-to-serosal flux ( J m→s) of all SCFA, decreases in serosal pH stimulated serosal-to-mucosal flux ( J s→m), and bilateral pH decreases stimulated both fluxes equally. These effects were observed whether the SCFA was present on one or both sides of the tissue, in both proximal and distal colon, in the absence of luminal Na+, and in the presence of either luminal or serosal ouabain. Changes in intracellular pH or intracellular [[Formula: see text]] did not account for the effects of extracellular pH. Luminal Cl− removal, to evaluate the role of apical membrane Cl−/SCFA−exchange, had no effect on J m→s but decreased J s→m 32% at pH 6.5 and 22% at 7.2. Increasing SCFA concentration from 1 to 100 mM, at pH 6.4 or 7.4, caused a linear increase in J m→s. We conclude that SCFA are mainly transported across the rat colon by nonionic diffusion.

Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice

“…One has to be aware of the dominant SCFA/HCO3-exchange (34) perturbing the recordings. In addition, there is non-ionic diffusion of butyrate into the colonocytes (35). Because these components of colon butyrate transport cannot be inhibited selectively, the contribution of both components to overall colon butyrate transport is still not clear (36).…”

“…These results are probably due to the dominant uptake of butyrate by SCFA/bicarbonate exchanger activity (34) and nonionic diffusion (35). Both uptake mechanisms are well described in colon although it is not clear to which proportion they contribute to colon butyrate uptake (36), because both pathways cannot be inhibited specifically.…”

Short-Chain Fatty Acids Induce Colonic Mucosal Injury in Rats with Various Postnatal Ages

“…The chemical property of SCFAs may be responsible for the injurious effect of SCFAs on intestinal mucosa. At pH 4.0, which was chosen on the basis of the observation of Clark et al (15) that 16 of 17 patients with NEC had intraluminal contents with a pH of Ͻ5 (pH range, 3.8 -4.6), most of the SCFAs (weak organic acids) are in free acid form and are most likely absorbed into intestinal mucosal cells via diffusion (18). The osmolarity of each SCFA solution was similar and within the isotonic range; furthermore, in our previous study, using 300 mM of lactic acid at pH 4.0 with the final osmolarity increased to 500 mOsmol/L did not induce any identifiable colonic mucosal injury in 9-to 10-d-old newborn rats (5).…”

News from the End of the Gut-How the Highly Segmental Pattern of Colonic HCO3- Transport Relates to Absorptive Function and Mucosal Integrity

“…63) However, experiments in rat colon showed no dependence of Cl Ϫ dependent HCO 3 Ϫ secretion on extracellular pH or HCO 3 Ϫ concentration on either side of the epithelium, and no satiability for up to 100 mM. 82) These findings are not compatible with an exclusive carrier-mediated SCFA absorptive process and lend support to the previously long-standing hypothesis that nonionic diffusion is involved, at least additionally. It may well be that the relative percentage of active and passive SCFA absorption is not absolute, but adaptable to the environmental circumstances, such as driving force, blood HCO 3 Ϫ concentration, surface pH, and the fatty acid composition that the commensal bacteria produce under a given nutrient load.…”