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P Lin
CSULA
Jan. 20, 2006

Nutrient Control of Gastrointestinal Transit-a Bench-to-Bedside Story
Henry C. Lin, MD
Division of Gastrointestinal and Liver Diseases
Keck School of Medicine,
University of Southern California
Los Angeles, CA

This lecture will be focused on the physiology of how nutrients control the movement of a mealthrough the gut. The goal of the seminar is to illustrate the bench-to bedside impact oftranslational research that link basic science to clinical medicine.

The following areas will be covered:
1. Control of upper gut transit by nutrient-triggered inhibitory feedback,
2. Examples of exploiting feedback control in nutritional support.
3. Clinical conditions associated with impaired transit control
4. Clinical consequences of uncontrolled transit
6. A novel, nutrient-based approach to the problem of accelerated transit.
The movement of food through the small intestine is tightly controlled via the triggering of
nutrient-triggered inhibitory feedback. Load-dependent slowing of gastric emptying is achieved
through a metering mechanism based on the length of nutrient spread (1).
Post-ulcer surgery is the classic example of accelerated gastric emptying. In that setting,
dumping symptoms are the consequences of exaggerated feedback response (2) secondary to
uncontrolled transit of the meal through the small intestine (3).
Fat-intolerant patients have similar complaints of postprandial symptoms of bloating, nausea and
diarrhea. We found that fat intolerant patients had accelerated gastric emptying to suggest that
their symptoms resulted from excessive nutrient-triggered feedback (4).
Once food is emptied, controlled transit through the small intestine becomes the next point of
regulation. There are 2 transit control mechanisms in the small intestine: the jejunal brake (5)
which is located in the proximal end of the small intestine and the more potent, ileal brake (6,7,8)
which is located in the distal end. Both of these controls are important since fat absorption
normally involves the proximal as well as the distal small intestine (9).
Impairment or loss of these transit controls have serious consequences including the dumping
syndrome and malnutrition, both resulting from accelerated intestinal transit. With accelerated
transit, digestion may be so impaired that the triggers for activating the transit controls are not
available.
Based on the therapeutic goal jump-starting the transit control response before a meal is
presented to the small intestine, a novel, nutrient-based therapy based on a premeal containing
Lin 2
fatty acids is effective in slowing intestinal transit in a dose-dependent fashion by activating
nutrient-triggered inhibitory feedback (10).
Since the time of residence in the small intestine (speed of intestinal transit) is also an important
determinant of the bioavailability of oral medications, inflammatory bowel disease (IBD)
patients with chronic diarrhea and accelerated transit may have poor absorption of oral drugs.
By slowing intestinal transit, a premeal containing fatty acids is effective in improving
bioavailability of oral medications (11). This strategy to increase the time available for
dissolution and absorption of oral drugs is also effective in normal subjects without accelerated
transit (12).
These results are quite encouraging since IBD and other diseases may be easier to treat than we
think if only we pay closer attention to the problem of accelerated transit, perform gut transit
testing to confirm this abnormality and work to bring transit under control.

REFERENCES
1. Lin HC, JE Doty, TJ Reedy, JH Meyer. Inhibition of gastric emptying by glucose
depends on the length of the intestine exposed to the nutrient. Am J Physiol 1989; 256:
G404-G411.
2. Lin HC. Abnormal intestinal feedback in disorders of gastric emptying. Dig Dis Sci,
1994;39:54S-55S.
3. Ralphs DNL, JPS Thomason, S Haynes, et al. The relationship between the rate of
gastric emptying and the dumping syndrome. Br J Surg 1978;65:637.
4. Lin HC, GW Van Citters, XT Zhao, A Waxman. Fat intolerance depends on rapid gastric
emptying. Dig Dis Sci 1999; 44:330-5
5. Lin HC, X-T Zhao, L-J Wang. Jejunal brake: inhibition of intestinal transit by fat in the
small intestine. Dig Dis Sci. 1996;41(2):326-329.
6. Read NW, A McFarlane, RI Kinsman, et al. Effect of infusion of nutrient solutions into
the ileum on gastrointestinal transit and plasma levels of neurotensin and enteroglucagon
in man. Gastroenterology 1984;86:274-280.
7. Spiller RC, IF Trotman, BE Higgins et al. The ileal brake-inhibition of jejunal motility
after ileal fat perfusion in man. Gut 1984;25:365-374.
8. Lin HC, X-T Zhao, L-J Wang. Intestinal transit is more potently inhibited by fat in the
distal (ileal brake) than proximal (jejunal brake) gut. Dig Dis Sci 1997;42:19-25
9. Lin HC, X-T Zhao, L-J Wang. Fat absorption is not complete by midgut but dependent
on load of fat. Am J Physiol 1996;271:G62-67.
10 Lin HC, G Van Citters, F Heimer, G Bonorris. Slowing of gastrointestinal transit by
oleic acid: A preliminary report of a novel, nutrient-based treatment for diarrhea.
(submitted) Dig Dis Sci.
11. Van Citters G, HC Lin. Oleic acid improves drug absorption in patients with
inflammatory bowel disease. Gastroenterology 1998;114(4):A1104.
12. Dobson CL, SS Davis, S Chauhan, RA Sparrow, IR Wilding. The effect of oleic acid on
the human ileal brake and its implication for small intestinal transit of tablet formulations.
Pharm Res 1999;16(1):92-96.

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