RESEARCH ARTICLEOpen Access
The effect of H. pylori eradication on meal-
associated changes in plasma ghrelin and leptin
Fritz Francois1,2*, Jatin Roper1, Neal Joseph1, Zhiheng Pei1,2, Aditi Chhada1, Joshua R Shak1,
Asalia Z Olivares de Perez1, Guillermo I Perez-Perez1and Martin J Blaser1,2
Background: Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric
mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori
eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight.
Methods: Veterans referred for upper GI endoscopy were evaluated at baseline and ≥8 weeks after endoscopy,
and H. pylori status and body weight were ascertained. During the first visit in all subjects, and during subsequent
visits in the initially H. pylori-positive subjects and controls, blood was collected after an overnight fast and 1 h
after a standard high protein meal, and levels of eight hormones determined.
Results: Of 92 enrolled subjects, 38 were H. pylori-negative, 44 H. pylori-positive, and 10 were indeterminate.
Among 23 H. pylori-positive subjects who completed evaluation after treatment, 21 were eradicated, and 2 failed
eradication. After a median of seven months following eradication, six hormones related to energy homeostasis
showed no significant differences, but post-prandial acylated ghrelin levels were nearly six-fold higher than pre-
eradication (p = 0.005), and median integrated leptin levels also increased (20%) significantly (p < 0.001). BMI
significantly increased (5 ± 2%; p = 0.008) over 18 months in the initially H. pylori-positive individuals, but was not
significantly changed in those who were H. pylori-negative or indeterminant at baseline.
Conclusions: Circulating meal-associated leptin and ghrelin levels and BMI changed significantly after H. pylori
eradication, providing direct evidence that H. pylori colonization is involved in ghrelin and leptin regulation, with
consequent effects on body morphometry.
The healthful regulation of energy homeostasis in humans,
depends on centrally-acting hormones such as ghrelin and
leptin [1,2]. Serum ghrelin concentrations increase during
fasting, and decrease after eating ; ghrelin decreases
energy expenditure and promotes weight gain . In con-
trast, leptin produced primarily by adipocytes, reduces
appetite and increases energy utilization . The gastric
epithelium expresses both ghrelin and leptin (and their
receptors) [6,7]; inflammation can modify their production
Helicobacter pylori, which colonizes the human sto-
mach and interacts with host tissues  may affect the
regulation of ghrelin and leptin . However, ghrelin and
leptin expression in H. pylori-colonized hosts has been
reported as reduced , or increased. Similarly, body
mass index (BMI) has been reported to be increased 
or reduced  following H. pylori eradication.
We hypothesized that gastric H. pylori colonization
affects the physiologic regulation of gut hormones
involved in food intake, energy expenditure, and body
weight maintenance. The hormones that affect overall
metabolic function include ghrelin, leptin, amylin, insu-
lin, active glucagon-like peptide-1, gastric inhibitory
polypeptide, peptide YY, and pancreatic polypeptide. We
used clinically indicated H. pylori eradication to evaluate
the effect of H. pylori on meal-associated changes in
ghrelin, leptin, and the other specified insulinotropic
and digestive hormones, and to assess post-eradication
changes in body mass index.
* Correspondence: Fritz.firstname.lastname@example.org
1New York University Langone Medical Center, New York, NY, USA
Full list of author information is available at the end of the article
Francois et al. BMC Gastroenterology 2011, 11:37
© 2011 Francois et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Adults ≥ 18 years of age undergoing routine upper
endoscopy for any indication at the ambulatory endo-
scopy unit at the New York campus of the VA New
York Harbor Healthcare System were prospectively
recruited, as described [9,14]. The Institutional Review
Board approved the study protocol, and written
informed consent was obtained from all participants.
Clinical evaluation and specimen collection
Each patient had a history and physical examination, and
fasted for 12-hours overnight prior to the endoscopy.
Demographic and clinical information, including assess-
ment of dyspeptic symptoms (Additional file 1), was
collected via a standardized questionnaire administered
by trained interviewers at the time of study entry. Ethnic
designation was self-reported by participants as White
Non-Hispanic, Black Non-Hispanic, Hispanic, or Asian.
Participants wore light clothing without shoes; height and
weight were measured using the same column scale with a
telescopic height rod, and BMI calculated. Between 8 am
and 10 am, 15 ml of blood was collected in EDTA-coated
tubes from the fasting patients prior to endoscopy. All
samples were centrifuged, and stored as serum at -20 C,
Complete endoscopic evaluation of the upper gastrointest-
inal tract was performed in standard fashion to the
2ndportion of the duodenum, after intravenous adminis-
tration of meperidine and midazolam, as described .
Gastric inflammation was graded using the Sydney-
Houston system . Using standard forceps, two biopsies
each were obtained from the gastric antrum, body, and
fundus in accordance with the updated Sydney classifica-
tion; two additional antral biopsies were used for rapid
One biopsy specimen from each of the three sites was
fixed in 10% formalin, embedded in paraffin, and 5 μm
consecutive sections obtained for histologic staining.
A single experienced GI pathologist (Z.P.) blinded to the
data, graded the extent of gastritis and intestinal metapla-
sia on a scale of 0 to 3+ according to the Sydney classifi-
cation . Active gastritis refers to the presence of
neutrophils in the histopathology, and chronic active
reflects both neutrophils and mononuclear cells. For
active gastritis, total score < 2 was defined as “low” while
≥ 2 was defined as “high”. H. pylori was detected using
the cresyl violet stain for the identification of spiral or
curved-shaped organisms near the mucous layer .
H. pylori status determination
Along with histologic evaluation and the rapid urease
assays, H. pylori was assessed using one other tissue-based
method (bacteriologic culture, as described) , and by
two serologic methods. Serum samples were examined by
ELISA for IgG antibodies to H. pylori whole cell and CagA
antigens, with results expressed as OD ratios relative to
laboratory standards, as described [19,20]. Subjects were
considered H. pylori-positive if positive by histologic
examination or culture, or if positive by rapid urease assay,
and by IgG antibodies to H. pylori group or CagA anti-
gens. Subjects were considered indeterminate for H. pylori
if only the rapid urease test or one serological test was
positive, consistent with prior studies .
Following recovery from endoscopy-related sedation, all
patients ate a high-protein non-commercial meal aver-
aging 806 calories. The contents of the meal were selected
with the guidance of a trained nutritionist to provide 72 g
carbohydrate, 71 g protein, and 26 g fat. Given that the
trough that occurs in serum ghrelin levels occurs one
hour postprandially , 15 ml of blood was collected one
hour after completing the meal, and processed as above.
H. pylori eradication therapy
Patients who tested positive for H. pylori were offered a
14-day twice-daily regimen [amoxicillin 1000 mg, clari-
thromycin 500 mg, and a proton pump inhibitor (PPI;
omeprazole 20 mg, rabeprazole or esomeprazole 40 mg)]
. Seven patients who had two positive serologic tests
were treated to eradicate H. pylori after further confirma-
tion with the13C Urea Breath Test while off antisecretory
medications. One penicillin-allergic patient received
metronidazole [500 mg twice a day] instead of amoxicillin.
In accordance with current guidelines , H. pylori eradi-
cation was ascertained using the13C Urea Breath Test,
according to the manufacturer’s instructions (Meretek
Diagnostics, Rockville, MD) ≥8 weeks after treatment
ended. At that time blood (15 ml) was again collected
after fasting and 1 hour after a standardized meal. Patients
who failed eradication were treated for 14 days with bis-
muth subsalicylate (525 mg four times a day), combined
with a twice daily regimen [tetracycline (500 mg), metroni-
dazole (500 mg), and PPI] . The13C Urea Breath Test
was repeated in all patients who completed rescue therapy.
If not clinically indicated, antisecretory medications were
not continued beyond the treatment period necessary for
A multi-hormone EIA panel (Catalogue HGT-68K;
Millipore Corp., Billerica MA) was used to quantify
Francois et al. BMC Gastroenterology 2011, 11:37
Page 2 of 9
eight gut hormones that are important regulators of
food intake [1,3,23], energy expenditure , and body
weight  via the gut-brain axis: acylated (active) ghre-
lin, leptin, active amylin, insulin, active glucagon-like
peptide-1 (GLP-1), total gastric inhibitory polypeptide
(GIP), total peptide YY (PYY), and pancreatic polypep-
tide (PP). We have previously reported a significant cor-
relation between this assay and a standard enzyme
linked immunoassay (EIA) for leptin (r = 0.57, p =
0.004). Similarly, we have found the correlation with a
standard ghrelin EIA to be significant [r = 0.37; p =
0.018 (data not shown)]. The intra- and inter-assay vari-
abilities ranged between11% and 19%, respectively,
according to the manufacturer, and for the ghrelin assay
no cross reactivity exists with desacyl ghrelin. All tests
were performed in duplicate on coded samples.
Continuous variables were compared using the t-test, or
ANOVA method, and pair-wise analyses (e.g. pre-meal vs.
post-meal, baseline vs. eradicated) were performed using
non-parametric tests (Wilcoxon’s signed rank test, Mann-
Whitney U test), as appropriate. Data are expressed as
mean ± SD, or median and interquartile range (25th- 75th
percentile). Categorical variables were compared using the
Chi-squared test with Yates’ correction or using Fisher’s
exact test. Spearman correlation coefficients were calcu-
lated for the relationship of leptin and ghrelin to BMI.
Corrections were made in instances of multiple compari-
sons using techniques such as Tukey’s range test. Based
on previous findings showing 75% increase in fasting ghre-
lin after H. pylori eradication , our study was powered
to allow for the detection of at least a 30% difference in
ghrelin levels following successful eradication of 15
patients. Statistical analysis was performed using SPSS
software version 16.0 for Macintosh (SPSS Inc., Chicago,
Illinois); a two-tailed p-value of < 0.05 was considered
Patient demographic and clinical characteristics
We enrolled 92 patients who completed the test meal pro-
tocol, as shown in Additional file 2, Figure S1. Based on
histologic, culture, and serologic results, 38 patients were
categorized as H. pylori-negative, 44 as H. pylori-positive,
and 10 were indeterminate (Table 1). Compared to
H. pylori-negative patients baseline BMI was significantly
higher among H. pylori-positive patients. The prevalence of
diabetes was also higher among H. pylori-positive com-
pared to H. pylori-negative patients, however this difference
did not reach statistical significance. The most common
indication for endoscopy in both the H. pylori-negative and
H. pylori-positive patients was heme-positive stool, and
persistent heartburn in the H. pylori-indeterminate group
(shown in Additional file 3, Table S1); PPI use occurred
in 46% of the entire study group. Endoscopic findings did
not differ significantly between the groups (Additional
file 3, Table S2). There were no significant changes in the
maintenance use of antisecretory medications between
baseline and follow-up examinations. We excluded the
H. pylori-indeterminate group from subsequent analyses.
The H. pylori-negative and -positive groups did not differ
significantly in age, ethnicity, PPI use, gender, or prevalence
of upper abdominal symptoms, (Table 1), but as expected,
they differed in extent of acute gastritis (Additional file 3,
Table S3). At baseline, the H. pylori-negative subjects had
lower BMI measurements than did the H. pylori-positive
group (26.4 ± 4 vs. 29.4 ± 5; p = 0.008). Stratifying the 44
H. pylori-positive hosts according to cagA status of their
strain did not reveal any significant differences in baseline
demographic and clinical parameters (data not shown).
Energy homeostasis hormones
The study subjects varied substantially in baseline pre-meal
(fasting) serum values for the eight studied hormones
(Additional file 3, Table S4). As expected, serum leptin
values correlated with BMI, for both the H. pylori-negative
and H. pylori-positive subjects (Additional file 2, Figure S2).
There were no significant differences according to H. pylori
status in pre-meal leptin, amylin, insulin, ghrelin, GIP,
GLP-1, PP, and PYY levels (Additional file 3, Table S4). As
expected, there were hormonal responses to the test meal;
post-meal amylin levels rose physiologically  in both
the H. pylori-negative and H. pylori-positive subjects (Addi-
tional file 3, Table S4). Similarly, there were significant
post-meal increases in the levels of insulin, GIP, PP, and
PYY, in both the H. pylori-negative and H. pylori-positive
groups. As expected , ghrelin values diminished follow-
ing the meal, while leptin values rose significantly in both
groups. Thus, our observations are consistent with the
expected meal-associated hormonal changes, with no sig-
nificant differences between the H. pylori-positive and
-negative subjects, as well as when data were normalized
(Additional file 3, Table S5).
Effects of H. pylori eradication
Treatment for H. pylori was accepted by 31 (70.5%) of the
44 subjects in whom it was clinically indicated; 23 com-
pleted all of our assessments and eradication was successful
in 21 (91%) (Additional file 2, Figure S1). The 21 subjects
were representative of the entire group of 44 who were
initially H. pylori-positive, with similar meal-associated
hormone changes at baseline (compare Table 2, and
Additional file 3, Table S4). Following H. pylori eradication,
the meal-associated increases in amylin, insulin, GIP, PP,
and PYY remained significant (Table 2). Compared
to baseline, post-meal levels of the incretin GLP-1 were sig-
nificantly increased following H. pylori eradication.
Francois et al. BMC Gastroenterology 2011, 11:37
Page 3 of 9
Pre-meal ghrelin levels did not significantly differ between
baseline and post-eradication (Table 2); however, following
H. pylori eradication, post-meal ghrelin levels did not sub-
stantially decrease (Figure 1A). After H. pylori eradication,
pre-meal, post-meal, and integrated leptin levels rose sig-
nificantly (Figure 1B), and remained significantly correlated
with BMI (r = 0.69, p < 0.01). PPI use did not account for
the changes in ghrelin and leptin levels from baseline to
follow-up (data not shown). This finding is consistent with
other reports that PPI use does not influence ghrelin levels
Since the initial measurements were performed on the
day of endoscopy while the second measurements were
not, we considered that gastric distension might have
influenced measurements between the two time-points.
We addressed this potential bias by also evaluating seven
subjects who were H. pylori negative at a second time-
point. The same test meal, and metabolic evaluations were
repeated in the seven H. pylori-negative subjects at base-
line and after follow-up (median 14 months). As expected,
this control group had no significant changes in the eight
measured adipokines between the two time-points (data
Table 1 Demographic and clinical characteristics of the 92 study patients, according to H. pylori status
(N = 38)(N = 10)
(N = 44)
Comparison of H. pylori-negative and
H. pylori-positive subjects (p-value)
Mean age (years) ± SD65 ± 1370 ± 6 64 ± 14
Male, n (%) 36 (95)10 (100)43 (98)
Race/ethnicity, n (%)
Mean BMI (kg/m2) ± SD
PPI use, n (%)a
26.4 ± 426.0 ± 329.4 ± 5 0.008b
15 (40)9 (90) 18 (41)
Diabetes, n (%)7 (18) 3 (30) 14 (32)
aPPI = proton pump inhibitor.
bStudent’s t-test;cChi-Squared test.
Table 2 Levels of eight hormones related to energy homeostasis, and BMI in 21 subjects, according to H. pylori
Median (IQR) hormone concentration (pg/ml), before and after H. pylori
Comparison of values at baseline and after
(14-43) (15-54)(15-50) (15-106)
(129-414) (462-1,475) (139-558)(430-2,100)
GLP-1 28160.5136450.95 0.11
(10-56) (9-59)(12-89) (14-91)
0.020.001 < 0.001
PP 63 107
ap-values < 0.05 are indicated in bold.
bWilcoxon’s signed rank test comparing pre-meal and post-meal values.
cPaired t-test comparing BMI at baseline to after H. pylori eradication.
Francois et al. BMC Gastroenterology 2011, 11:37
Page 4 of 9
not shown), and no changes in meal-associated physiology
(Figure 2). In the H. pylori-positive subjects at baseline,
ingestion of the test meal led to a 32 ± 9% decrease (p =
0.004) in ghrelin with somewhat larger declines in persons
with cagA-positive strains than in those with cagA-nega-
tive strains. Data from the 38 H. pylori-negative subjects
and the subset of seven who had long-term follow-up
also showed similar trends (Figure 2A). However, after
H. pylori eradication, post-meal ghrelin levels only fell
minimally (4 ± 12%; p = NS); the difference in meal-asso-
ciated responses comparing baseline and post-eradication
(32% vs. 4%) was significant (p = 0.05). At baseline, leptin
levels in both the H. pylori-positive and H. pylori-negative
subjects significantly increased after the test meal (Figure
2B). The meal-associated rise in leptin after eradication
(19 ± 7%), remained significant (p = 0.02). Following
H. pylori-eradication in subjects previously colonized with
cagA-positive strains, the expected meal-associated
increase in PP was significantly lower than expected (27%
vs. -13%; p = 0.01).
Meal-associated ghrelin physiology in relation to baseline
In the group from whom H. pylori was eradicated, the
severity of histologic inflammation in the fundus at
baseline was negatively correlated with pre-meal ghrelin
(r = -0.57, p = 0.01), as expected [29,30]. Subjects with
more active gastritis had higher pre-meal ghrelin levels
at baseline, and greater meal-associated changes post-
eradication (Additional file 3, Table S6). Eradication-
related changes in ghrelin physiology also correlated
with the anatomic location of gastritis; subjects with
antral gastritis only showed the largest increases in
values obtained pre-meal, post-meal, and across the
Figure 1 Comparison of H. pylori+ persons at baseline, and
then after eradication of H. pylori. A standardized meal was
administered to 21 subjects, and pre-meal, post-meal, and
integrated values (mean of pre-meal and post-meal) were calculated
for acyl-ghrelin (Panel A) and leptin (Panel B). H. pylori+(grey),
Eradicated (white). Boxes indicate median and interquartile range,
and bars indicate minimum and maximum values. P-values
represent significant (< 0.05) differences between the H. pylori+and
Figure 2 Comparison of test-meal induced changes in plasma
acyl-ghrelin and leptin levels according to H. pylori at baseline
and after eradication. Data are for seven H. pylori-negative, 21
H. pylori-positive subjects including eight H. pylori+cagA- and 13
H. pylori+cagA+ subjects. (* P < 0.05, comparing either pre-meal to
post-meal values, or **comparing the first and second evaluations).
Data also are shown for all of the 38 H. pylori-negative subjects at
baseline, for comparison with the subset who also had follow-up
studies. Panel A: Ghrelin levels. Panel B: Leptin Levels.
Francois et al. BMC Gastroenterology 2011, 11:37
Page 5 of 9
meal (Additional file 3, Table S7). These data provide
evidence that both location and extent of gastric inflam-
mation affects ghrelin secretion, but similar associations
were not found with reference to leptin physiology (data
Body mass index in relation to H. pylori status
Since baseline BMI was higher for the H. pylori-eradicated
group, we addressed this potential bias by comparing indi-
viduals to themselves in longitudinal pair-wise analyses.
During the six months prior to study initiation, BMI did
not change substantially in any of the study subjects
(Figure 3). During 18 months (IQR 12, 24) of follow-up,
BMI did not change significantly in subjects who at
baseline were either H. pylori-negative or H. pylori-
indeterminate. In contrast, in the H. pylori-eradicated
group, BMI progressively and significantly increased,
reaching 105 ± 2% by 18 months of follow-up (p = 0.008);
baseline H. pylori cagA status did not predict results (p =
0.58). The change in BMI relative to baseline also was
significantly greater at 3, 6, and 12 months following eradi-
cation compared to the H. pylori-negative group (data not
shown). The change in pre-meal ghrelin from baseline fol-
lowing H. pylori eradication, was positively correlated with
the change in BMI at 3 months (r = 0.78; p = 0.005),
6 months (r = 0.86; p = 0.001), and 12 months [r = 0.82;
p = 0.001 (Additional file 2, Figure S3)], and 18 months
(r = 0.87; p = 0.001).
Dyspepsia symptoms at baseline and follow-up
Since weight gain could reflect decreased dyspeptic
symptoms following H. pylori eradication, we assessed
dyspeptic symptoms at baseline and post-eradication.
A validated multidimensional assessment tool  was
used to evaluate three scales: pain intensity, non-pain
symptoms, and satisfaction with dyspepsia-related
health. At baseline, the 38 H. pylori-negative and 44
H. pylori-positive subjects did not differ significantly in
median pain, non-pain, and satisfaction scores (data not
shown). Among the 21 patients from whom H. pylori
was eradicated, there were no significant differences
between baseline and follow-up pain scores [Median
(IQR) 9 (2-23) vs. 6 (2-15); p = 0.86], non-pain scores
[13 (12-16) vs. 10 (10-18); p = 0.28], or satisfaction
scores [13 (10-23) vs. 19 (12-20); p = 0.29]. Thus, the
observed increase in BMI following eradication (Figure 3)
was not correlated with diminished dyspepsia that could
Appetite-reducing hormones, such as amylin, insulin, GIP,
GLP-1, PP, and PYY, produced in the small intestine and
pancreas are important in mammalian energy homeostasis,
[32-35], as is leptin which is produced mostly by adipo-
cytes, but also by gastric chief cells . Importantly, gastric
oxyntic endocrine cells  account for 65-80% of the
body’s total ghrelin production. H. pylori colonization
status has been correlated with circulating and gastric
mucosal leptin levels , and with gastric mRNA expres-
sion and plasma levels of ghrelin [9,37]. We now identified
substantial effects of H. pylori eradication on meal-
associated changes in gastric hormones and energy
balance, confirming and extending prior studies in a more
rigorous manner [13,38].
That H. pylori-positive and H. pylori-negative subjects
had similar baseline digestive hormonal physiologies
(Additional file 3, Table S4) may reflect the highly inte-
grated cross-regulation of energy homeostasis,  and
the long-term equilibria between H. pylori and individual
hosts [10,40]. Our observations of high pre-meal levels of
acylated (acyl-) ghrelin that then fell post-prandially were
as expected . However, several months after H. pylori
eradication, the extent of physiologic meal-associated
reduction in circulating acyl-ghrelin was much diminished.
These findings are consistent with other studies of subjects
who underwent H. pylori eradication and then had
increased plasma ghrelin [13,30,38] and gastric ghrelin
mRNA levels . Alterations in ghrelin regulation follow-
ing H. pylori eradication may reflect the extent of baseline
gastric inflammation . Similarly, plasma levels of acyl-
ghrelin may be significantly elevated post-H. pylori eradi-
cation, and vary reflecting the severity of atrophic gastritis
, but atrophic gastritis is uncommon in the population
we studied (data not shown). Methodological issues across
studies, such as the length of follow-up post-H. pylori
treatment [11,29] and differences in populations examined
Change in BMI as a percent
Time (months) in relation to baseline
Figure 3 Change in BMI in 69 study subjects over a 2-year
period. BMI is calculated relative to the baseline (at time 0), and is
shown from 6 months prior to baseline and during 18 months of
follow-up in 38 H. pylori-negative, 21 H. pylori-eradicated, and 10
subjects who were H. pylori-indeterminate at baseline (*p < 0.05,
comparing time 0 to other follow-up months).
Francois et al. BMC Gastroenterology 2011, 11:37
Page 6 of 9
 may partially account for differing metabolic and
anthropometric findings. We now provide evidence that
the extent and location of H. pylori-induced inflammation
at baseline is associated with the differences in ghrelin
physiology that develop due to H. pylori eradication.
Although our data must be considered preliminary with
small numbers of subjects, baseline antral gastritis appears
to affect responses to eradication.
Although ghrelin is known to induce weight gain, in a
study with six weeks of follow-up after H. pylori eradica-
tion, plasma ghrelin was increased, but median BMI was
unchanged . In another study, 12 weeks following
H. pylori eradication, plasma ghrelin was increased in
some subjects and reduced in others .
Our study now shows that following H. pylori eradica-
tion, there is blunting of the meal-associated physiologic
reduction in circulating acyl-ghrelin, and there is long-
term weight gain; in addition, changes in baseline acyl-
ghrelin values and changes in BMI were linked (Additional
file 2, Figure S3). Reflecting the observed weight gain,
leptin levels pre-meal and post-meal ghrelin levels were
significantly elevated after eradication and differed signifi-
cantly from baseline values. We also observed that
H. pylori eradication was associated with preservation of
the expected [26,41-43] meal-associated increases in amy-
lin, insulin, GIP, PP, and PYY. Post-meal levels of the
incretin GLP-1 were significantly increased following era-
dication compared to baseline, perhaps reflecting the need
for a meal-termination signal in the setting of persistently
elevated ghrelin levels. We found no evidence that the
weight gain associated with H. pylori eradication reflected
improvement of dyspeptic symptoms as suggested
previously . Although in our study group, the
H. pylori-positive subjects had higher BMIs at baseline
compared to H. pylori-negative, the study was not
designed to compare BMI between H. pylori-negative and
H. pylori-positive groups. Rather, we sought to compare
the change in BMI over time within the groups.
Our findings are limited by the study setting at a veter-
an’s hospital where most of the evaluated patients were
older men. Measurement of ghrelin is not standardized,
 and may account for the substantial inter-individual
variation that we report. However, comparing each sub-
ject to himself before and after the standard test meal,
and repeating the same measurements at baseline and
during follow-up reduces the effects of inter-individual
variation, as well as any potential effect of the endoscopic
evaluation performed on all patients. We also verified
measurements in the same individuals in duplicate on
separate occasions. Since all patients (H. pylori-negative
and H. pylori-positive) had an endoscopic evaluation
prior to the first postprandial measurement of hormones,
and not prior to the second postprandial measurement,
the observed post-eradication changes could not be
explained by the potential effect of the endoscopic exami-
nation alone. We measured acyl-ghrelin, which also may
be relevant in energy homeostasis following H. pylori
eradication, as opposed to total ghrelin as others have
done [11,29]. We did not address changes in the ratio of
circulating active versus inactive ghrelin before and after
eradication. Other strengths of the study include the col-
lection of detailed demographic, clinical, and histologic
data from a prospectively enrolled group using validated
instruments, H. pylori status determination using multi-
ple methods for all patients that improve sensitivity and
diminish falsely negative categorization , measure-
ment of eight gut hormones to ascertain the meal-
associated metabolic profile of each subject at baseline,
and following up an H. pylori-negative group for compar-
ison. We planned to analyze patients who were not
successfully treated to eradicate H. pylori, however few
individuals failed eradication therapy and thus that
control group was not sufficiently populated. In addition,
our ability to further analyze H. pylori-negative patients
was limited by the fact that only 7 completed follow-up
In conclusion, our study indicates that leptin and ghre-
lin physiology change and that BMI increases following
H. pylori eradication. Although the number of subjects
is limited, using patients as their own controls and hav-
ing multiple measurements allowed us to both confirm
previous published data, and to use a standard meal
technique to extend the findings. This study provides
further evidence that gastric H. pylori is involved in the
physiologic regulation of these hormones, and supports
the rationale for randomized controlled H. pylori eradi-
cation trials to focus on the role of inflammation and
endocrine cross-talk in explaining these findings.
Additional file 1: Supplemental methods. Provides information
regarding exclusion criteria for the study population, symptom
evaluation, H. pylori evaluation, test meal, and metabolic tests.
Additional file 2: Supplemental figures. Provides information regarding
the enrollment and classification of study participants (Figure S1), the
relationship of baseline BMI and baseline pre-meal leptin according to
H. pylori status (Figure S2), and the correlation of changes in ghrelin and
BMI post-H. pylori eradication (Figure S3).
Additional file 3: Supplemental tables. Provides information regarding
the indications for upper GI endoscopy among study subjects (Table S1),
findings during upper endoscopy (Table S2), Histologic score at three
gastric sites according to H. pylori status (Table S3), levels of eight
hormones related to energy homeostasis at the baseline evaluation of
subjects according to H. pylori status and in relation to the test meal
(Table S4), test-meal induced change and normalized change in
hormone profile according to H. pylori status at baseline (Table S5),
comparison of baseline and post-eradication meal-associated ghrelin
profile in 21 originally H. pylori-positive subjects according to severity of
Francois et al. BMC Gastroenterology 2011, 11:37
Page 7 of 9
baseline histologic gastritis (Table S6), and meal-associated changes in
ghrelin profile in 28 subjectsawho had follow-up evaluation according to
anatomical distribution of histologic gastritis at baseline (Table S7).
Supported in part by K23CA107123, R01GM63270, R01DK090989,
NCRRM01RR0096, and 1UL1RR029893 from the National Institutes of Health,
the Michael Saperstein Medical Scholars Program, and the Diane Belfer
Program in Human Microbial Ecology. We thank the NYU School of
Medicine Division of Gastroenterology, its fellows, and nurses for their
1New York University Langone Medical Center, New York, NY, USA.2New
York Harbor Veteran Affairs Medical Center, New York, NY, USA.
All authors read and approved the final manuscript. FF participated in the
design of the study, patient recruitment, sample procurement, statistical
analysis, and manuscript preparation. JR participated in patient recruitment,
sample processing, and manuscript preparation. NJ contributed with patient
recruitment and with manuscript preparation. ZP was involved in review of
pathology samples and manuscript. AC participated in patient recruitment
and manuscript review. JRS participated in sample processing and
manuscript preparation. AZO was involved in sample procurement and
processing as well as manuscript review. GIP participated in sample
processing and manuscript preparation. MJB participated in study design,
analysis, and manuscript preparation.
The authors declare that they have no competing interests.
Received: 15 September 2010 Accepted: 14 April 2011
Published: 14 April 2011
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The pre-publication history for this paper can be accessed here:
Cite this article as: Francois et al.: The effect of H. pylori eradication on
meal-associated changes in plasma ghrelin and leptin. BMC
Gastroenterology 2011 11:37.
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