GASTROENTEROLOGY 79X76-1262,19&I
Transit of a Meal Through the Stomach,
Small Intestine, and Colon in Normal
Subjects and its Role in the Pathogenesis
of Diarrhea
N. W. READ, C. A. MILES, D. FISHER, A. M. HOLGATE,
N. D. KIME, M. A. MITCHELL, A. M. REEVE, T. B. ROCHE,
and M. WALKER
Departments of Physiology and Gastroenterology, University of Sheffield, Sheffield,
England
A method for measuring the transit time of a meal,
containing sausages, mashed potato, baked beans,
and a pineapple custard dessert, through the gastro-
intestinal tract was evaluated in 14 healthy volun-
teers. Gastric emptying was determined by incorpo-
rating a radioactive marker in the meal and counting
over the surface of the stomach using a crystal scin-
tillation detector. Small intestinal transit time was
determined by measuring breath hydrogen excretion
and by estimating the radioactivity over the cecum.
Finally, whole gut transit time was measured by in-
corporating radiopaque plastic markers or carmine
red in the meal and estimating the appearance of
these markers in the stool. Our results showed that
measurements of small intestinal transit time were
reproducible and in the majority of subjects the in-
crease in hydrogen excretion occurred at the same
time as the increase in radioactive counts over the
surface of the cecum. The passage of the first marker
in the stool coincided with the appearance of car-
mine red. There were no significant correlations be-
tween small intestinal transit time and whole gut
transit time or the half time for gastric emptying. ln-
corporation of 10, 25, and 40 g lactulose into our
standard meal in place of sucrose increased the rate
of transit through the small intestine but did not sig-
nijicantly alter the rate of gastric emptying or the
Received December 31, 1979. Accepted June 23, 1960.
Address requests for reprints to: Dr. N. W. Read, Department of
Physiology, University of Sheffield, Sheffield, England.
This study was carried out as a Physiology class project for the
Dual Honours B.Sc. students.
The authors gratefully acknowledge the expert technical assist-
ance of Mrs. Christine Brown and Mrs. Norma Hobson. They also
thank Dr. I. Bergman, Dr. D. Barber, and Dr. S. Sheriff for the loan
of the equipment.
0 1966 by the American Gastroenterological Association
09165965/&J/121276-07gO2.25
whole gut transit time. Total stool weight for 48 hr
after ingestion of the meal was inversely related to
whole gut transit time but not to small intestinal
transit time suggesting that the tendency to develop
diarrhea in response to a meal containing unabsorb-
able carbohydrate depends more on the lack of co-
ionic accommodation than on the rate of small in-
testinal transit. Finally, there was no significant
correlation between the measurements of small in-
testinal transit time after a drink of lactulose and
the transit time of a meal in the same subjects.
It is not uncommon to find patients with disordered
bowel habit for which routine diagnostic tests fail to
reveal the cause.“2 Such patients are often suspected
of having some disorder of intestinal motility result-
ing in an abnormal transit of food through the in-
testine and impaired absorption of fluid. However,
there is no acceptable and physiologically relevant
method for measuring the transit of food through
various portions of the gut. The transit time of a
meal from mouth to anus, measured by counting in-
gested markers in stool specimens>4 is dominated by
the slow rate of transit through the colon and does
not give any indication of the more rapid transit
through the small intestine, where most absorption
occurs. Current methods for measuring small in-
testinal transit time involve ingestion of barium sul-
fate5*’ or the osmotic laxative, lactulose (Duphalac)’
and the results do not necessarily relate to the tran-
sit of food through the small intestine. In this study
we have described a method for determining di-
rectly the transit times of a single meal through the
stomach, the small intestine, and the colon in normal
volunteers. This method has been used to investigate
December 1980
the pathogenesis of the osmotic diarrhea induced by
ingestion of unabsorbable carbohydrate.
Materials and Methods
Subjects
Studies were carried out on 14 young, healthy sub-
jects (3 female, 11 male; average age = 22 yr). Each subject
gave written informed consent for each experiment to be
performed and the study was approved by the Ethical sub-
committee of the Sheffield Area Health Authority (South-
ern Region) on July 2, 1979.
The subjects fasted for at least 12 hr before each test.
Composition of the Meal
The meal used in this study was of homogeneous
consistency and did not readily separate into solid and liq-
uid phases. It contained three hot-dog sausages (60 g), 150
g of mashed potato, 120 g of baked beans, and a dessert
consisting of homogenized pineapple sweetened with su-
crose and thickened with custard powder (75 g). The total
weight of the meal was 405 g, and the caloric intake was
536 kcals. Sips of water up to a total volume of 50 ml were
allowed with the meal. Fifty microcuries of gsmtechnetium-
sulfur colloid (half life = 6 hr) were incorporated in the
mashed potato, together with 50 radiopaque plastic
markers (sections of tubing 0.4 cm x 0.2 cm). Baked beans
contained the undigestible oligosaccharides, stachyose
and raffinose, which served as substrates for hydrogen
production in the large intestine.8 Four grams of carmine
red were mixed with the beans fed to 5 subjects.
Rate of Ingestion
The meal was placed on a preweighed plate on a
top-loading balance, and the weight was noted at minute
intervals as the subject ate.
Gastric Emptying
Gastric emptying was measured in all 14 subjects
using a single crystal scintillation detector connected to a
count ratemeter.’ This method had previously been shown
to give as good an index of gastric emptying as the gamma
camera while using only a fraction of the radiation dose
(50 &i vs. 1500 PCi)? After the food had been ingested, the
subject lay on his back, and the scintillation detector was
carefully positioned over the area of greatest radioactivity.
Counts were then measured for 1 min every 2 min. The
test was terminated when the activity (after correction for
decay of the isotope) had decreased to one-third of the
original value.
In one series of six experiments the marker was incor-
porated in the solid phase of the meal by labeling chicken
liver using the method described by Meyer et al.” The
chicken liver was cooked in a microwave oven for 5 set,
diced into cubes, 0.5 cm square, and a 20-g portion was
eaten in place of an equivalent weight of sausage.
When gastric emptying results were plotted (counts per
MEAL TRANSIT AND DIARRHEA 1277
minute vs. time), a graph resembling an exponential curve
was usually obtained. Points on this curve beyond those
which were measured were obtained by extrapolating the
linear transformation of the data on a semilogarithmic
plot. Half-times for gastric emptying were obtained from
both the direct and semilogarithmic plots.
Measurement of small intestinal transit time.
Small intestinal transit time was estimated in all 14 sub-
jects by measuring the excretion of hydrogen in the
breath’ using a metallized membrane e1ectrode.l’ Every 5
min throughout the test an alveolar air sample was ob-
tained using a Haldane-Priestley tube.” The sample of ex-
haled air was injected into the electrode via a drying agent
and a simple chromatographic column to separate the rap-
idly moving hydrogen from any carbon monoxide present
(also detected by the electrode). To confirm that the in-
crease in hydrogen excretion was related to the arrival of
the food in the colon, radioactivity was measured in all 14
subjects using a second crystal scintillation detector posi-
tioned in the right iliac fossa over a point 2 cm medial to
the anterior superior iliac spine.
Whole gut transit and stool analysis. Whole gut
transit time was determined in all 14 subjects. Stools were
collected during the study and for at least 2 days after-
tiards. The results of each bowel movement were col-
lected in separate polyethylene bags which were labeled
with a tag stating the date and time that the stools had
been passed. Each separate motion was inspected for the
presence of carmine red and x-rayed to determine the
number of plastic markers. Each 24-hr collection was
weighed, and the consistency was noted on a scale from
solid or formed to viscous (like thick soup or porridge) to
frank liquid.
Experiments Using Lactulose
In three separate series of experiments carried out
in 6 normal subjects, 10 g, 25 g, and 40 g of the indigestible
disaccharide lactulose (15, 37.5, and 60 ml, Duphalac, Phil-
lips Duphar, Weesp, Holland) were incorporated into the
pineapple puree dessert in place of equal amounts of su-
crose. Gastric emptying and small intestinal transit time
were measured in each experiment, but stool weight and
whole gut transit time were measured only after ingestion
of 40 g lactulose.
Gastric emptying and small intestinal transit time were
also determined in 11 subjects after ingestion of 10 g lactu-
lose in 400 ml of water. The methods were the same as
those used for the solid meal.
Statistical Analysis
The degree of statistical significance between sets
of data collected under differing conditions in the same
subjects was determined using Student’s paired t-test.
Results
Control Experiments
Rate of ingestion. Each subject ate the meal
within 7 min, and there was no correlation between
1278 READ ET AL. GASTROENTEROLOGY Vol. 79, No. 6

tied exponentially with an average of half-time of

little over 1 hr (1.32 f 0.13 hr; mean f SEM, range =
0.60-2.33 hr; median = 1.20 hr, n = 14). It made no
significant difference to the results if the half-time
was obtained from the direct or semilogarithmic
plots.
The rate of emptying of the marker incorporated
into the solid part of the meal in 6 subjects by label-
ing chicken liver (t?4 = 1.15 f 0.13 hr), was not sig-
nificantly different from the rate of emptying of the
marker incorporated in the mashed potato in the
same subjects (t% = 1.22 f 0.16 hr).
. Small intestinal transit. All 14 subjects mani-
.
fested increases in hydrogen excretion after inges-
2. tion of the meal. A typical record of hydrogen excre-
tion after ingestion of the standard meal is shown in
Figure 1. Two hydrogen peaks were observed after
ingestion of the meal. The primary peak was brief
and occurred shortly after ingestion (26 f 4 min)
(while most of the meal was in the stomach). The
secondary peak was larger, started to rise between 2
0 1 2 3 4 5 6 7 8 9 l0 11 I2 and 7 hr after the meal (mean = 3.9 + 0.4 hr, range =
1.5-7.4 hr, median = 4.0 hr, n = 14) reach a maxi-
TIME(hr) mum between 5 and 11 hr (mean = 6.3 & 0.4 hr,
range = 3.3-10.9 hr, median = 6.2 hr) and decayed
towards basal values around 12 hr after ingestion.
The primary peak was not related to entry of the
meal into the cecum because it was not associated
with any rise in radioactivity over the cecal area
(Figure 1). Neither could it be explained by bacterial
overgrowth in the small intestine because in our ex-
perience the early increase in breath hydrogen in
that condition is sustained for several hours after in-
gestion of the meal. We tested the possibility that
01 -t
the enhanced colonic motility induced by feeding’”
0 1 2 3 4 5 6 7 8 3 10 II 12
either released hydrogen trapped in the fecal mass
TIME (hr) or exposed sequestered carbohydrate to the action
Figure 1. Comparison of breath hydrogen excretion and gastric of bacteria, by feeding a steak meal at the very end
and cecal radioactivity. In the upper graph, the radio- of a control study after hydrogen excretion had re-
active counts over the surface of the stomach (open cir- turned to basal levels. This manoeuvre did not in-
cles) and cecum (closed circles), expressed as a per- duce any increase in hydrogen excretion. In our
centage of the gastric counts measured immediately
after ingestion of the test meal are plotted against the
opinion the most likely explanation for this primary
time after ingestion of the meal. The lower graph increase in hydrogen excretion is that ingestion of
shows the relationship between the concentration of the meal caused the passage of a portion of the meal
hydrogen excreted in the breath and the time after in- eaten the night before into the cecum.
gestion of the meal. The values were obtained from 1 There was a highly significant correlation be-
normal subject. Note that the first rise in breath hydro-
gen occurs at a time when there is no increase in radio-
tween the time of the increase in radioactivity (r =
activity over the cecum, while the secondary rise in 0.82; P < 0.001) over the cecum and the time of the
breath hydrogen concentration corresponds with the secondary increase in hydrogen excretion. In nine
rise in cecal radioactivity. out of fourteen subjects, the secondary increase in
H, excretion occurred at the same time as the in-
crease in cecal radioactivity indicating that measure-
the rate of ingestion and the rates of gastric empty- ment of breath hydrogen is a useful method to in-
ing or small intestinal transit. dicate when a meal enters the colon. The
Gastric emptying. When technetium was in- observation that the increase in cecal radioactivity
corporated in the mashed potato, the stomach emp- preceded the rise in hydrogen excretion in the re-
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1280 READ ET AL. GASTROENTEROLOGY Vol. 79, No. 6

Small lntesttnal Transit TlmQ (hr)

SW-

600 .

.
.
400 . .
0
00
0

. + :
Figure 2. The relationship between the total
.
zco-
weight of feces passed during the
.
48 hr after ingestion of the meal
0 .
and the small intestinal transit time
. . (top) and the time of elimination of
0 I -t the first plastic marker in the stool
I 2 3 4 5 6 7 8 (whole gut transit time; bottom).
The closed circles are measure-
800.
WhOlQ Gut Transit Time (hr) ments made after ingestion of the
standard meal. The open circles re-
fer to measurements made after the
@lo- meal containing 40 g lactulose.

ux)-

200.

0
. .
24 46 72 96 I20 144

hr). There was no significant correlation (r = 0.31; P
> 0.1) between transit time determined by the in-
crease in hydrogen excretion after ingestion of the
standard me’al and that determined after ingestion of
400 g of water containing 10 g of lactulose.
Incorporation of lactulose in the standard
meal. Although incorporation of increasing doses of
lactulose in the standard meal in place of sucrose in-
creased the rate of gastric emptying (Table 1)the re-
sults were not significantly different from the emp-
tying of the standard meal alone. Increasing the dose
of lactulose, however, significantly decreased the
time between the ingestion of the meal and both the
secondary increase in hydrogen production and the
peak hydrogen production (Table 1) and sub-
stantially increased the maximum concentration
hydrogen in the breath samples. Despite the reduc-
tion in small intestinal transit time, replacement of
sucrose by 40 g of lactulose did not alter the average
rate of elimination of fecal markers (Table 1).
Relationship between intestinal transit and
stool weight. There was an inverse curvilinear rela-
tionship (Figure 2) between the whole gut transit of
radiopaque markers (first marker, 50% and 100%
markers), and the weight of feces was collected over
48 hr after ingestion of the meal (I: values for log
whole gut transit time vs. log 2 day stool weight
< 0.75). This relationship was present even when the
data from the control meal or the meal containing 40
g lactulose were analyzed separately. There was no
curvilinear or linear correlation between stool
weight and small intestinal transit time (Figure 2).
Inspection of Figure 2 also shows that subjects re-
sponded in dramatically different ways to incorpora-
tion of lactulose in the meal. One subject passed
nearly 800 ml of liquid feces after ingestion of 40 g of
lactulose and commenced passing markers 8 hr after
the meal. Another subject who passed only 90 g of
solid feces during the 48 hr after lactulose, did not
of pass any markers for 6 days. The small intestinal
transit time in these subjects differed by only 30 min.
Discussion
The aim of this study was to develop and
evaluate a method for measuring the transit of food
through the stomach, small intestine, and large in-
testine in humans. The method chosen was designed
December 1980
to be physiologically relevant and simple to carry
out. Clearly the results obtained in this study relate
only to the composition of the meal we used, and
different results may be obtained with meals of dif-
ferent composition or weight. For example, the rea-
son why other workers” have noted very different
gastric emptying curves for liquid and solid com-
ponents of the meal whereas we found that liquid
and solid labels emptied at similar rates must de-
pend on the relative composition of the meals used.
If the meal is clearly differentiated into solid and liq-
uid phases, these will empty at different rates,” but,
if the meal is of homogeneous consistency, the solid
and liquid components will not necessarily separate
in the stomach and will empty at similar rates.14
The close correspondence between cecal radio-
activity and measurements of breath hydrogen sug-
gests that the secondary increase in hydrogen excre-
tion may indicate the time when the head of the
meal enters the cecum’ (small intestinal transit time)
while in at least 50% of the subjects peak hydrogen
excretion indicates the time when the bulk of the
meal was entered the colon. If this is the case, then
the observation that these two times are closely cor-
related supports the idea that measurement of the
secondary increase in breath hydrogen excretion
provides an index of the transit time of the bulk as
well as the head of the meal.
We could not demonstrate any direct correlation
between the transit time of the meal and the transit
time of a solution of lactulose in the same subjects.
This suggests that transit measurements after inges-
tion of a drink of lactulose do not provide a useful
index of the transit of food through the small in-
testine and are not necessarily of relevance in eval-
uating the role of small intestinal transit in condi-
tions which give rise to malabsorption, diarrhea, or
constipation. On the other hand, the measurement of
the transit of a standard meal offers direct insight
into the role of small intestinal transit of food in
these conditions.
The increase in the rate of transit of the meal
through the small intestine induced by incorporation
of lactulose in place of sucrose can for the most part
be explained by an increase in the volume of the
meal caused by osmotic inhibition of fluid absorp-
tion by the unabsorbed carbohydrate. This would
stimulate peristalsis and hence propulsion of the
meal. It is of note that despite the accelerated small
intestinal transit, increasing the amount of lactulose
in the meal did not increase the rate of transit of the
meal through the whole gut. This, together with the
lack of correlation between the rates of transit of the
standard meal through stomach, small intestine, and
whole gut suggests that the rate of transit through
each portion of the gastrointestinal tract is con-
MEAL TRANSIT AND DIARRHEA 1281
trolled by its own independent mechanism. This
does not however rule out the possibility that these
control mechanisms could be overwhelmed by the
delivery of a large volume of fluid, caused by exces-
sively rapid transit of food through a more proximal
segment of gut. Such an event could contribute to
the diarrhea observed in short bowel syndrome or in
conditions causing abnormal secretion in the small
bowel or the rapid small intestinal transit observed
in some patients after partial gastrectomy.”
The observations that the Z-day stool weight was
inversely correlated to whole gut transit but not to
small intestinal transit, suggest that under our exper-
imental conditions, transit of material through the
colon is more important in the pathogenesis of os-
motic diarrhea than transit through the small gut. In-
deed, the results of studies adding 40 g of lactulose
(60 ml Duphalac) to the meal showed that although
small intestinal transit time was reduced by about
50% in all subjects, some were able to accommodate
the rapid delivery of this amount of undigested car-
bohydrate and its attendant fluid load in the colon
and were still able to produce normal stools. Other
subjects could not accommodate this load in the co-
lon and developed rapid colonic transit and diar-
rhea. Among the factors which may influence co-
ionic accommodation to the rapid delivery of this
meal are the sensitivity of the cecum to distension
and the ability of the colonic flora to metabolize car-
bohydrate to short chain fatty acids, which may
then be rapidly absorbed.16
Differences in colonic accommodation may ex-
plain why only some patients with disorders of car-
bohydrate digestion, such as lactase deficiency, or
disorders of carbohydrate absorption, such as celiac
sprue, develop diarrhea while others may even be-
come constipated, and why some patients fail to re-
spond to osmotic laxatives such as lactulose.
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