Desensitization of ileal vagal receptors by short-chain fatty acids in pigs.

Coloileal reflux episodes trigger specialized ileal motor activities and inhibit gastric motility in pigs. The initiation of these events requires the detection by the distal ileum of the invading colonic contents that differ from the ileal chyme primarily in short-chain fatty acid (SCFA) concentrations. In addition to the already described humoral pathway, this detection might also involve ileal vagal afferents. Sensitivity to SCFA of 12 ileal vagal units was investigated in anesthetized pigs with single-unit recording at the left cervical vagus. SCFA mixtures (0.35, 0.7, and 1.4 mol/l) containing acetic, propionic, and butyric acids in proportions identical to that in the porcine cecocolon were compared with isotonic and hypertonic saline. All units behaved as slowly adapting mechanoreceptors (half-adaptation time = 35.4 +/- 15.89 s), and their sensitivity to local mechanical probing was suppressed by local anesthesia; 7 units significantly decreased their spontaneous firing with 0.7 and 1.4 but not 0.35 mol/l SCFA infusion compared with hypertonic or isotonic saline. Similarly, the response induced by distension in the same seven units was reduced (5 neurons) or abolished (2 neurons) after infusion of 0.7 (22.8 +/- 2.39 impulses/s) and 1.4 (30.3 +/- 2.12 impulses/s) mol/l SCFA solutions compared with isotonic saline (38.6 +/- 4.09 impulses/s). These differences in discharge were not the result of changes in ileal compliance, which remained constant after SCFA. In conclusion, SCFA, at concentrations near those found during coloileal reflux episodes, reduced or abolished mechanical sensitivity of ileal vagal afferents.

Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway.

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 +/- 1.2 vs. 49 +/- 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 +/- 0.11 vs. 1.3 +/- 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 +/- 1.0 and 34 +/- 0. 8 vs. 47 +/- 1.3 and 43 +/- 1.2%; frequency, 1.4 +/- 0.07 and 1.6 +/- 0.06 vs. 1.1 +/- 0.14 and 1.0 +/- 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

Short-chain fatty acids present in the ileum inhibit fasting gastrointestinal motility in conscious pigs.

Colonic compounds, primarily short-chain fatty acids (SCFAs), inhibit gastric tone in humans. However, since colonic compounds reflux into the ileum, SCFAs might act also at the ileal level. This study evaluates the effects of the contact of SCFAs with the ileum alone towards gastrointestinal motility in fasted conscious pigs. Gastrointestinal motility was recorded during ileal infusion of a mixture containing acetate, propionate and butyrate in intact vs ileostomized animals (n = 10). Ileal infusions of isomolar (500 mmol L-1) vs isocaloric (600 kJ L-1) SCFAs were also performed. SCFA mixture reduced significantly the amplitude and increased the frequency of antral contractions in intact (motility index: 2624 +/- 503.4 vs 4077 +/- 388.2) and ileostomized pigs (motility index: 2428 +/- 678.1 vs 4709 +/- 773.4) compared with iso-osmotic saline. SCFAs at isomolar concentrations inhibited equally gastric motor pattern irrespective of their chemical structure. On the contrary, isocaloric concentrations of SCFAs induced graded effects: acetic acid being the most potent to reduce gastric motility. In conclusion, SCFAs inhibit gastrointestinal motility by a direct contact with the ileum. This inhibition was concentration dependent.

Ileal short-chain fatty acids inhibit transpyloric flow in pigs.

BACKGROUND: Short-chain fatty acids (SCFA) found in the ileum after caecoileal reflux might trigger a physiologic ileal brake similar that induced by ileal nutrient infusion. This study evaluates gastric emptying and motility after ileal administration of SCFA. METHODS: In eight conscious pigs gastric emptying was evaluated by double dilution (liquids) and direct measurement of duodenal effluent (liquids and solids) during ileal infusions of SCFA and isotonic and hypertonic saline. Antropyloroduodenal manometry and flow were recorded concurrently. RESULTS: Ileal SCFA significantly delayed gastric emptying of liquids and solids. During SCFA infusion the emptying pattern of liquids was less pulsatile, and flow pulses had a smaller stroke volume than during isotonic saline. The antroduodenal pressure gradient was decreased, whereas pyloric tone was increased. A reduced number of antral pressure waves occurred together with an increased frequency of isolated pyloric pressure waves. CONCLUSIONS: Ileal SCFA infusion delays gastric emptying of liquid and solid as a consequence of a decreased antral and increased pyloric motility.

Relationships between cecoileal reflux and ileal motor patterns in conscious pigs.

Ileal infusion of cecocolonic contents, used to mimick reflux, enhanced terminal ileal motility, increasing the frequencies of prolonged propagated contractions (PPC) and discrete clustered contractions (DCC). Because the reflux rate in dogs and humans is marginal, the relationship of these motor patterns to reflux remained putative. In six conscious pigs, the ileal pH, used to indicate reflux event, was measured 10 and 5 cm proximal to the ileocecal sphincter (ICS). Ileal motility was evaluated with three strain gauges 15, 10, and 5 cm proximal to the ICS. Ileal pH dips were observed about eight times per hour in the fasting or fed state, and 46% of the pH dips were preceded by a retrograde contraction. During pH dips, frequency of ileal contractions not classified as PPC or DCC was significantly increased. Of the PPC 52% occurred immediately after the start of the dip and might act as a clearance mechanism because dips associated with PPC were of smaller amplitude and duration than those not associated with PPC. Most DCC also occurred during pH dips but their delay to the onset of the dip was longer. The pig presents frequent cecoileal reflux events associated with ileal motor patterns, some of them might facilitate reflux, whereas others act as a clearance mechanism.