Skip to main content
Log in

Ileal brake: Neuropeptidergic control of intestinal transit

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Digestion and absorption of a meal are time-intensive processes. To optimize digestion and absorption, transit of the meal through the gastrointestinal tract is regulated by a complex integration of neuropeptidergic signals generated as the jejunal brake and ileal brake response to nutrients. Mediators involved in the slowing of transit responses include peptide YY (PYY), chemosensitive afferent neurons, intestinofugal nerves, noradrenergic nerves, myenteric serotonergic neurons, and opioid neurons. The activation of this circuitry modifies the peristaltic reflex to convert the intestinal motility pattern from propagative to segmenting. Fat is the most potent trigger of these transit control mechanisms. The integrated circuitry of gut peptides and neurons involved in transit control in response to nutrients is described in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Holgate AM, Read NW: Can a rapid small bowel transit limit absorption? Gut 1982, 23:A912.

    Google Scholar 

  2. Lin HC, Doty JE, Reedy TJ, Meyer JH: Inhibition of gastric emptying by glucose depends on length of intestine exposed to nutrient. Am J Physiol 1989, 256:G404-G411

    PubMed  CAS  Google Scholar 

  3. Lin HC, Doty JE, Reedy TJ, Meyer JH: Inhibition of gastric emptying by sodium oleate depends on length of intestine exposed to nutrient. Am J Physiol 1990, 259:G1031-G1036.

    PubMed  CAS  Google Scholar 

  4. Zhao XT, Miller RH, McCamish MA, et al.: Protein absorption depends on load-dependent inhibition of intestinal transit in dogs. Am J Clin Nutr 1996, 64:319–323.

    PubMed  CAS  Google Scholar 

  5. Spiller RC, Trotman IF, Adrian TE, et al.: Further characterisation of the "ileal brake" reflex in man—effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY. Gut 1988, 29:1042–1051.

    PubMed  CAS  Google Scholar 

  6. Meyer JH, Kelly GA: Canine pancreatic responses to intestinally perfused proteins and protein digests. Am J Physiol 1976, 231:678–681.

    PubMed  CAS  Google Scholar 

  7. Meyer JH, Kelly GA, Jones RS: Canine pancreatic responses to intestinally perfused oligopeptides. Am J Physiol 1976, 231:682–691.

    PubMed  CAS  Google Scholar 

  8. Lin HC, Zhao XT, Wang L: Jejunal brake: inhibition of intestinal transit by fat in the proximal small intestine. Digest Dis Sci 1996, 41:326–329.

    Article  PubMed  CAS  Google Scholar 

  9. Read NW, McFarlane A, Kinsman RI, et al.: Effect of infusion of nutrient solutions into the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon. Gastroenterology 1984, 86:274–280.

    PubMed  CAS  Google Scholar 

  10. Spiller RC, Trotman IF, Higgins BE, et al.: The ileal brake-inhibition of jejunal motility after ileal fat perfusion in man. Gut 1984, 25:365–374.

    PubMed  CAS  Google Scholar 

  11. Woolf GM, Miller C, Kurian R, Jeejeebhoy KN: Diet for patients with a short bowel: high fat or high carbohydrate? Gastroenterology 1983, 84:823–828.

    PubMed  CAS  Google Scholar 

  12. Lin HC, Zhao XT, Wang L: Intestinal transit is more potently inhibited by fat in the distal (ileal brake) than in the proximal (jejunal brake) gut. Digest Dis Sci 1997, 42:19–25.

    Article  PubMed  CAS  Google Scholar 

  13. Reynell P, Spray G. Small intestinal function in the rat after massive resections. Gastroenterology 1956, 31:361–368.

    PubMed  CAS  Google Scholar 

  14. Kremen AJ, Linner JH, Nelson CH. An experimental evaluation of the nutritional importance of proximal and distal small intestine. Ann Surg 1954, 140:439–448. Fat maldigestion/malabsorption is worse when the distal versus proximal half of the small intestine is taken out of continuity.

    Article  PubMed  CAS  Google Scholar 

  15. Lin HC, Zhao XT, Chu AW, et al.: Fiber-supplemented enteral formula slows intestinal transit by intensifying inhibitory feedback from the distal gut. Am J Clin Nutr 1997, 65:1840–1844. Fiber-supplemented enteral formula slows intestinal transit by displacing nutrients to the more potent ileal brake response.

    PubMed  CAS  Google Scholar 

  16. Jain NK, Boivin M, Zinsmeister AR, et al.: Effect of ileal perfusion of carbohydrates and amylase inhibitor on gastrointestinal hormones and emptying. Gastroenterology 1989, 96:377–387.

    PubMed  CAS  Google Scholar 

  17. Jain NK, Boivin M, Zinsmeister AR, DiMagno EP: The ileum and carbohydrate-mediated feedback regulation of postprandial pancreaticobiliary secretion in normal humans. Pancreas 1991, 6:495–505.

    Article  PubMed  CAS  Google Scholar 

  18. Lin HC, Kim BH, Elashoff JD, et al.: Gastric emptying of solid food is most potently inhibited by carbohydrate in the canine distal ileum. Gastroenterology 1992, 102:793–801.

    PubMed  CAS  Google Scholar 

  19. Lin HC, Moller NA, Wolinsky MM, et al.: Sustained slowing effect of lentils on gastric emptying of solids in humans and dogs. Gastroenterology 1992, 102:787–792.

    PubMed  CAS  Google Scholar 

  20. Zhao XT, McCamish MA, Miller RH, et al.: Intestinal transit and absorption of soy protein in dogs depend on load and degree of protein hydrolysis. J Nutr 1997, 127:2350–2356.

    PubMed  CAS  Google Scholar 

  21. Shankardass K, Chuchmach S, Chelswick K, et al.: Bowel function of long-term tube-fed patients consuming formulae with and without dietaryfiber. JPEN J Parenter Enter Nutr 1990, 14:508–512.

    CAS  Google Scholar 

  22. Siegle ML, Ehrlein HJ: Digestive motor patterns and transit of luminal contents in canine ileum. Am J Physiol 1988, 254:G552-G559.

    PubMed  CAS  Google Scholar 

  23. Brown NJ, Read NW, Richardson A, et al.: Characteristics of lipid substances activating the ileal brake in the rat. Gut 1990, 31:1126–1129.

    PubMed  CAS  Google Scholar 

  24. Cherbut C, Aube AC, Blottiere HM, Galmiche JP: Effects of short-chain fatty acids on gastrointestinal motility. Scand J Gastroenterol 1997, 222(Suppl):58–61.

    CAS  Google Scholar 

  25. Meyer JH, Elashoff JD, Domeck M, et al.: Control of canine gastric emptying of fat by lipolytic products. Am J Physiol 1994, 266:G1017-G1035.

    PubMed  CAS  Google Scholar 

  26. Homann HH, Kemen M, Fuessenich et al.: Reduction in diarrhea incidence by soluble fiber in patients receiving total or supplemental enteral nutrition. JPEN J Parenter Enter Nutr 1994, 18:486–490.

    Article  CAS  Google Scholar 

  27. Nakao M, Ogura Y, Satake S, et al.: Usefulness of soluble dietary fiber for the treatment of diarrhea during enteral nutrition in elderly patients. Nutrition 2002, 18:35–39.

    Article  PubMed  Google Scholar 

  28. Bueno L, Praddaude F, Fioramonti J, Ruckebusch Y: Effect of dietary fiber on gastrointestinal motility and jejunal transit time in dogs. Gastroenterology 1981, 80:701–707.

    PubMed  CAS  Google Scholar 

  29. Eisenberg P: An overview of diarrhea in the patient receiving enteral nutrition. Gastroenterol Nursing 2002, 25:95–104.

    Article  Google Scholar 

  30. Spapen H: Soluble fiber reduces the incidence of diarrhea in septic patients receiving total enteral nutrition: a prospective, double-blind, randomized, and controlled trial. Clin Nutr 2001, 20:301–305.

    Article  PubMed  CAS  Google Scholar 

  31. Postuma R: Extreme short-bowel syndrome in an infant. J Pediatr Surg 1983, 18:264–268.

    Article  PubMed  CAS  Google Scholar 

  32. Mei N: Recent studies on intestinal vagal afferent innervation. Functional implications. J Autonom Nerv Syst 1983, 9:199–206.

    Article  CAS  Google Scholar 

  33. Randich A: Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat. Am J Physiol Regul Integr Compar Physiol 2000, 278:R34-R43.

    CAS  Google Scholar 

  34. Anthone GJ, Wang BH, Zinner MJ, et al.: Meal-induced jejunal absorption requires intact neural pathways. Am J Surg 1992, 163:150–156.

    Article  PubMed  CAS  Google Scholar 

  35. Lin HC, Chen JH: Slowing of intestinal transit by fat depends on an oxethezaine-sensitive afferent pathway. Gastroenterology 2002, 122:A62.

    Google Scholar 

  36. Stanley S, Wynne K, Bloom: Gastrointestinal satiety signals III. Glucagon-like peptide 1, oxyntomodulin, peptide YY, and pancreatic polypeptide. Am J Physiol-Gastrointest Liver Physiol 2004, 286: G693-G697.

    Article  PubMed  CAS  Google Scholar 

  37. Lin HC, Zhao XT, Wang L, Wong H: Fat-induced ileal brake in the dog depends on peptide YY. Gastroenterology 1996, 110:1491–1495.

    Article  PubMed  CAS  Google Scholar 

  38. McDonald TJ, Wang YF, Mao YK, et al.: PYY: a neuropeptide in the canine enteric nervous system. Regul Pept 1993, 44:33–48.

    Article  PubMed  CAS  Google Scholar 

  39. Lin HC, Wang LJ, Zhao XT: Slowing of intestinal transit by fat in proximal gut depends on peptide YY. Neurogastroenterol Motil 1998, 10:82A.

    Google Scholar 

  40. Lin HC, Chey WY: Cholecystokinin and peptide YY are released by fat in either proximal or distal small intestine in dogs. Regul Pept 2004, 114:131–135.

    Article  CAS  Google Scholar 

  41. Greeley GH Jr, Jeng YJ, Gomez G, et al.: Evidence for regulation of peptide-YY release by the proximal gut. Endocrinology 1989, 124:1438–1443.

    Article  PubMed  CAS  Google Scholar 

  42. McFadden DW, Rudnicki M, Kuvshinoff B, Fischer JE: Postprandial peptide YY release is mediated by cholecystokinin. Surg Gynecol Obstetr 1992, 175:145–150.

    CAS  Google Scholar 

  43. Lin HC, Chey WY, Zhao X: Release of distal gut peptide YY (PYY) by fat in proximal gut depends on CCK. Peptides 2000, 21:1561–1563.

    Article  PubMed  CAS  Google Scholar 

  44. Lin HC, Taylor IL: Release of peptide YY in the proximal but not distal gut depends on atropine-blockable cholinergic pathway. Regul Pept 2004, 117:73–76.

    Article  PubMed  CAS  Google Scholar 

  45. Chuo S, Jeng J, Farrar S, et al.: Neural control of peptide YY release. Gastroenterology 1990, 98:A653.

    Google Scholar 

  46. Schutte IW, Akkermans LM, Kroese AB: CCKA and CCKB receptor subtypes both mediate the effects of CCK-8 on myenteric neurons in the guinea-pig ileum. J Autonom Nerv Syst 1997, 67:51–59.

    Article  Google Scholar 

  47. Sternini C, Wong H, Pham T, et al.: Expression of cholecystokinin A receptors in neurons innervating the rat stomach and intestine. Gastroenterology 1999, 117:1136–1146

    Article  PubMed  CAS  Google Scholar 

  48. Gulley S, Covasa M, Ritter RC, Sayegh AI: Cholecystokinin1 receptors mediate the increase in Fos-like immunoreactivity in the rat myenteric plexus following intestinal oleate infusion. Physiol Behav 2005, 86:128–135. CCK-1 receptor antagonist abolished myenteric FOS-like immunoreactivity stimulated by oleate or glucose.

    Article  PubMed  CAS  Google Scholar 

  49. Lucaites VL, Mendelsohn LG, Mason NR, Cohen ML: CCK8, CCK-4 and gastrin-induced contractions in guinea pig ileum: evidence for differential release of acetylcholine and substance P by CCK-A and CCK-B receptors. J Pharmacol Exp Ther 1991, 256:695–703.

    PubMed  CAS  Google Scholar 

  50. Zelles T, Harsing LG, Vizi ES: Characterization of neuronal cholecystokinin receptor by L-364,718 in Auerbach’s plexus. Eur J Pharmacol 1990, 178:101–104.

    Article  PubMed  CAS  Google Scholar 

  51. Corsi M, Palea S, Pietra C, et al.: A further analysis of the contraction induced by activation of cholecystokinin A receptors in guinea pig isolated ileum longitudinal muscle-myenteric plexus. J Pharmacol Exp Ther 1994, 270:734–740.

    PubMed  CAS  Google Scholar 

  52. Koda S, Date Y, Murakami N, et al.: The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 2005, 146:2369–2375.

    Article  PubMed  CAS  Google Scholar 

  53. Mao YK, Wang YF, Ward G, et al.: Peptide YY receptor in submucosal and myenteric plexus synaptosomes of canine small intestine. Am J Physiol 1996, 271:G36-G41. PYY receptors were localized to myenteric and submucosal neurons of canine small intestine.

    PubMed  CAS  Google Scholar 

  54. Blackshaw LA: Effects of 5-hydroxytryptamine on discharge of vagal mucosal afferent fibres from the upper gastrointestinal tract of the ferret. J Autonom Nerv Syst 1993, 45:41–50.

    Article  CAS  Google Scholar 

  55. Blackshaw LA: Effects of 5-hydroxytryptamine (5-HT) on the discharge of vagal mechanoreceptors and motility in the upper gastrointestinal tract of the ferret. J Autonom Nerv Syst 1993, 45:51–59.

    Article  CAS  Google Scholar 

  56. Furness JB, Koopmans HS, Robbins HL, Lin HC: Identification of intestinofugal neurons projecting to the coeliac and superior mesenteric ganglia in the rat. Autonom Neurosci-Basic Clin 2000, 83:81–85.

    Article  CAS  Google Scholar 

  57. Zhu JX, Zhu XY, Owyang C, Li Y: Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat. J Physiol 2001, 530:431–442.

    Article  PubMed  CAS  Google Scholar 

  58. Grider JR: 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons. Am J Physiol 1996, 270:G778-G782.

    PubMed  CAS  Google Scholar 

  59. Kellum JM, Albuquerque FC, Stoner MC, Harris RP: Stroking human jejunal mucosa induces 5-HT release and Cl-secretion via afferent neurons and 5-HT4 receptors. Am J Physiol 1999, 277:G515-G520.

    PubMed  CAS  Google Scholar 

  60. Uneyama H, Niijima A, Tanaka T, Torii K: Receptor subtype specific activation of the rat gastric vagal afferent fibers to serotonin. Life Sci 2002, 72:415–423.

    Article  PubMed  CAS  Google Scholar 

  61. Conte D, Legg ED, McCourt AC, et al.: Transmitter content, origins and connections of axons in the spinal cord that possess the serotonin (5-hydroxytryptamine) 3 receptor. Neuroscience 2005, 134:165–173.

    Article  PubMed  CAS  Google Scholar 

  62. Lin HC, Chen JH: Slowing of intestinal transit by fat depends on an ondansetron-sensitive, efferent serotonergic pathway. Neurogastroenterol Motil 2003, 15:317–322. In contrast to reports from in vitro experiments, intestinal serotonin slows intestinal transit via 5-HT3 receptors in whole animals.

    Article  PubMed  CAS  Google Scholar 

  63. Szurszewski J, Weems W: A study of peripheral input to and its control by post-ganglionic neurones of the inferior mesenteric ganglion. J Physiol 1976, 256:541–556. Intestino-intestinal inhibitory reflex depends on extrinsic nerves that synapse at the prevertebral ganglion.

    PubMed  CAS  Google Scholar 

  64. Lin HC, Perdomo OL, Fisher H: Slowing of intestinal transit by fat is reversed by 5-HT3 or 5-HT4 receptor antagonists in the rat. Gastroenterology 2001, 120:A224.

    Google Scholar 

  65. Lin HC, Neevel C, Chen PS, et al.: Slowing of intestinal transit by fat or peptide YY depends on beta-adrenergic pathway. Am J Physiol Gastrointest Liver Physiol 2003, 285:G1310-G1316. Slowing of intestinal transit by fat or PYY depends on a noradrenergic pathway acting on ß1-adrenoreceptors expressed by selected myenteric neurons.

    PubMed  CAS  Google Scholar 

  66. Wood JD, Galligan JJ: Function of opioids in the enteric nervous system. Neurogastroenterol Motil 2004, 16:17–28.

    Article  PubMed  Google Scholar 

  67. Zhao XT, Wang L, Lin HC: Slowing of intestinal transit by fat depends on naloxone-blockable efferent, opioid pathway. Am J Physiol Gastrointest Liver Physiol 2000, 278:G866-G870. Enteric opioid interneurons are involved in the postprandial response to fat.

    PubMed  CAS  Google Scholar 

  68. Lin HC, Zaidel O, Hum S: Intestinal transit of fat depends on accelerating effect of cholecystokinin and slowing effect of an opioid pathway. Digest Dis Sci 2002, 47:2217–2221.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Henry C. Lin MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van Citters, G.W., Lin, H.C. Ileal brake: Neuropeptidergic control of intestinal transit. Curr Gastroenterol Rep 8, 367–373 (2006). https://doi.org/10.1007/s11894-006-0021-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-006-0021-9

Keywords

Navigation