• Eradication
• Helicobacter pylori
• Metabolic syndrome
• Sex

• Ghrelin
• atrophic gastritis
• gastric cancer
• intestinal metaplasia
• pepsinogen

Background: Antibiotic therapy used to eradicate Helicobacter pylori has been associated with changes in plasma ghrelin and alterations in the gut microbiota. On the other hand, changes in ghrelin levels have been related to changes in gut microbiota composition. Our aim was to evaluate the relationship between changes in the gut microbiota and ghrelin levels in H. pylori infected patients who received antibiotic treatment for its eradication.

Methods: A prospective case-control study that included forty H. pylori-positive patients who received eradication therapy (omeprazole, clarithromycin, and amoxicillin) and twenty healthy H. pylori antigen-negative participants. Patients were evaluated, including clinical, anthropometric and dietary variables, before and 2 months after treatment. Gut microbiota composition was analyzed through 16S rRNA amplicon sequencing (IlluminaMiSeq).

Results: Changes in gut microbiota profiles and decrease in ghrelin levels were identified after H. pylori eradication treatment. Gut bacteria such as Bifidobacterium longum, Bacteroides, Prevotella, Parabacteroides distasonis, and RS045 have been linked to ghrelin levels fasting and/or post meals. Changes in the abundance of Lachnospiraceae, its genus Blautia, as well as Prevotella stercorea, and Megasphaera have been inversely associated with changes in ghrelin after eradication treatment.

Conclusions: Eradication treatment for H. pylori produces changes in the composition of the intestinal microbiota and ghrelin levels. The imbalance between lactate producers such as Blautia, and lactate consumers such as Megasphaera, Lachnospiraceae, or Prevotella, could trigger changes related to ghrelin levels under the alteration of the eradication therapy used for H. pylori. In addition, acetate producing bacteria such as B. longum, Bacteroides, and P. distasonis could also play an important role in ghrelin regulation.

• Helicobacter pylori
• antibiotic
• eradication treatment
• ghrelin
• gut microbiota

Plasma ghrelin level is influenced by Helicobacter pylori (H. pylori) status and the severity of gastric mucosal atrophy, and the ghrelin level is associated with nutrition status in hemodialysis patients. Here, we investigated the efficacy of H. pylori eradication therapy in improving nutrition status in relation to the ghrelin level in H. pylori-positive hemodialysis patients. Of H. pylori-positive patients receiving hemodialysis at 8 dialysis center, 21 patients underwent gastroduodenoscopy for evaluation of the severity of gastric atrophy, and nutrition markers and plasma ghrelin levels before and 1 year after H. pylori eradication therapy were evaluated. Serum cholinesterase level was significantly increased after H. pylori eradication compared with the level before eradication (303.2 ± 76.0 vs 287.3 ± 68.1 IU/L, p = 0.029). In particular, cholesterol (before, 196.6 ± 23.2 mg/dl; after, 206.1 ± 25.9 mg/dl, p = 0.042) and cholinesterase levels (before, 296.9 ± 70.8 IU/L; after, 316.4 ± 73.8 IU/L, p = 0.049) increased more strongly in patients with mild–moderate atrophy than those with severe atrophy, irrespective of improvement of plasma acyl-ghrelin and desacyl-ghrelin levels after eradication therapy. In conclusion, H. pylori eradication may improve nutrition status by increasing serum cholinesterase and cholesterol levels in hemodialysis patients, especially those with mild and moderate gastric mucosal atrophy.

• Helicobacter pylori
• eradication
• ghrelin
• hemodialysis
• nutritional marker

Chronic kidney disease (CKD) patients receiving hemodialysis (HD) often develop gastrointestinal abnormalities over their long treatment period. In general, prognosis in such patients is poor due to the development of protein-energy wasting (PEW). Therefore, it is important to clarify the etiology of PEW and to establish better strategies to deal with this condition. Chronic Helicobacter pylori (H. pylori) infection in the gastric mucosa has a close association with not only the development of peptic ulcer disease and gastric cancer, but is also associated with abnormal plasma and gastric mucosal ghrelin levels that are seen in malnutrition. It is unclear whether H. pylori infection of the gastric mucosa is directly associated with prognosis in HD patients by affecting ghrelin levels. Recent studies show that the prevalence of H. pylori infection in HD patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in HD patients, the prevalence of infection decreases as the length of time on HD increases. The severity of gastric mucosal atrophy has been suggested as the major determinant of ghrelin levels in these patients, and eradication therapy of H. pylori improves nutritional status by increasing serum cholinesterase and cholesterol levels, especially in patients with mild-to-moderate gastric mucosal atrophy. Prompt H. pylori eradication to inhibit the progress of gastric atrophy may be required to prevent this decrease in ghrelin levels and subsequent PEW and improve the prognosis of HD patients by improving their nutritional status.

• Helicobacter pylori
• Hemodialysis
• Ghrelin
• Gastric mucosa
• Anti-bacterial agents

• Anti-Bacterial Agents/therapeutic use
• Atrophy/metabolism
• Atrophy/microbiology
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Ghrelin/blood
• Helicobacter Infections/drug therapy
• Helicobacter Infections/epidemiology
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter pylori/drug effects
• Helicobacter pylori/isolation & purification
• Humans
• Nutritional Status
• Prevalence
• Prognosis
• Renal Dialysis/adverse effects
• Renal Insufficiency, Chronic/metabolism
• Renal Insufficiency, Chronic/therapy
• Time Factors
• Wasting Syndrome/blood
• Wasting Syndrome/metabolism
• Wasting Syndrome/microbiology
• Wasting Syndrome/prevention & control

Small intestinal bacterial overgrowth (SIBO) may coexist with Helicobacter pylori infection, which can be the cause of chronic gastrointestinal complaints.

Evaluation of the therapeutic efficacy of amoxicillin and rifaximin in the treatment of these diseases.

The lactulose hydrogen breath test (LHBT) and the urea breath test (¹³C-UBT) were performed in 116 patients. In 62 patients the coexistence of small intestinal bacterial overgrowth and H. pylori infection was observed. Then, in group I (n = 30) pantoprazole (2 × 40 mg), amoxicillin (2 × 1000 mg) and metronidazole (2 × 500 mg) and in group II (n = 32) pantoprazole and amoxicillin at the above doses and rifaximin (3 × 400 mg) were administered for 10 days. After 6 weeks, both breath tests were repeated and the degree of remission of symptoms was measured using a 10-point visual analog scale (VAS).

After the treatment the LHBT index decreased in group I from 61.2 ±19.4 ppm to 22.0 ±8.2 ppm (p < 0.001) and in group II from 59.6 ±15.5 ppm to 15.2 ±8.6 ppm (p < 0.001). Eradication of H. pylori (¹³C-UBT below 4.0‰) was achieved in 63.3% of patients in group I and 59.4% in group II (p > 0.05). The decrease of pain below 3.0 points in the VAS was obtained in 64.8% of patients in group I and in 56.2% in group II.

Combination of amoxicillin and rifaximin may be effective in the treatment of patients with small intestinal bacterial overgrowth syndrome and concomitant H. pylori infection.

• Helicobacter pylori
• amoxicillin
• rifaximin
• small intestinal bacterial overgrowth
• therapy

To investigate the influence of antimicrobials on both the gut microbiota structure and the plasma ghrelin level using Helicobacter pylori-infected patients who underwent eradication therapy.

Twenty H. pylori-infected patients (mean age 68.3 years old) who underwent eradication therapy participated in the study. For the therapy, patients had 1 week of triple therapy consisting of amoxicillin, clarithromycin and proton-pump inhibitors. Stool and blood samples were obtained before (S1), immediately after (S2) and/or 3 months after (S3) the therapies. The concentrations of ghrelin and leptin in the blood were assayed using an ELISA. The V3-V4 region of the 16S rRNA gene was amplified using bacterial DNA from the stool, and about 50 000 high-quality amplicons per sample were grouped into operational taxonomic units for bacteriological analyses.

The Bacteroidetes:Firmicutes (B:F) ratio was significantly greater at S3 than S1 (P<0.01). This increase in the B:F ratio between S3 and S1 was found in 15 out of 20 patients. A significant decrease in the concentration of active ghrelin (P=0.003) in the plasma was observed between S3 and S1. There was a statistically significant correlation between the rate of patients whose B:F ratio increased and that of patients whose active ghrelin level decreased between S3 and S1 according to Fisher’s exact probability test (P=0.03).

Changes in the gut microbiota, such as the B:F ratio after treatment with antimicrobials, might cause a change in the plasma ghrelin level, as the direct and earliest target of antimicrobials would be the microbiota rather than the hormone-secreting system.

• antibiotic therapy
• helicobacter pylori
• intestinal microbiology
• obesity

To investigate the relationship between plasma ghrelin level, Helicobacter pylori (H. pylori) infection status and the severity of atrophy in hemodialysis patients.

One hundred eights patients who received hemodialysis and 13 non-hemodialysis H. pylori-negative controls underwent gastroduodenoscopy to evaluate the severity of gastric atrophy. Serum levels of pepsinogen (PG) were measured as serum markers of gastric atrophy. H. pylori infection was evaluated by anti-H. pylori IgG antibody, rapid urease test and culture test. We classified H. pylori infection status as non-infection, present infection and past infection. In addition, plasma acyl-ghrelin and desacyl-ghrelin levels were measured by enzyme-linked immunosorbent assay.

Infection rate of H. pylori was 45.4% (49/108). Acyl-ghrelin level in the non-infection group (39.4 ± 23.0 fmol/mL) was significantly higher than in the past (23.4 ± 19.9 fmol/mL, P = 0.005) and present infection groups (19.5 ± 14.0 fmol/mL, P < 0.001). Furthermore, desacyl-ghrelin level in the non-infection group (353.2 ± 190.2 fmol/mL) was significantly higher than those in the past (234.9 ± 137.5 fmol/mL, P = 0.008) and present infection groups (211.8 ± 124.2 fmol/mL, P < 0.001). Acyl-ghrelin was positively correlated with the PG I level and PG I/II ratio (|R| = 0.484, P < 0.001 and |R| = 0.403, P < 0.001, respectively). Both ghrelins were significantly decreased in accordance with the progress of endoscopic atrophy (both P < 0.001) and acyl-ghrelin was significantly lower in patients with mild, moderate and severe atrophy (24.5 ± 23.1 fmol/mL, 20.2 ± 14.9 fmol/mL and 18.3 ± 11.8 fmol/mL) than in those with non-atrophy (39.4 ± 22.2 fmol/mL, P = 0.039, P = 0.002 and P < 0.001, respectively).

In hemodialysis patients, plasma ghrelin level was associated with the endoscopic and serological severity of atrophy related to H. pylori infection.

• Acyl-ghrelin
• Desacyl-ghrelin
• Helicobacter pylori
• Hemodialysis
• Pepsinogen

• Aged
• Atrophy
• Biomarkers/blood
• Breath Tests
• Case-Control Studies
• Duodenoscopy
• Enzyme-Linked Immunosorbent Assay
• Female
• Gastric Mucosa/metabolism
• Gastric Mucosa/microbiology
• Gastric Mucosa/pathology
• Gastritis, Atrophic/blood
• Gastritis, Atrophic/diagnosis
• Gastritis, Atrophic/microbiology
• Gastroscopy
• Ghrelin/blood
• Helicobacter Infections/blood
• Helicobacter Infections/diagnosis
• Helicobacter Infections/microbiology
• Helicobacter pylori/isolation & purification
• Humans
• Male
• Middle Aged
• Nutritional Status
• Pepsinogen A/blood
• Predictive Value of Tests
• Renal Dialysis

Helicobacter pylori (H. pylori) infection and eradication therapy have been known to influence gastric ghrelin and leptin secretion, which may lead to weight gain. However, the exact relationship between plasma ghrelin/leptin levels and H. pylori infection has remained controversial. The aim of this study was to investigate plasma ghrelin and leptin levels in H. pylori-positive and -negative patients, to compare the two levels of the hormones before and after H. pylori eradication, and to examine the correlation between body mass index (BMI) and active ghrelin or leptin levels, as well as that between atrophic pattern and active ghrelin or leptin levels.

Seventy-two H. pylori-positive patients who underwent upper gastrointestinal endoscopy, 46 diagnosed as having peptic ulcer and 26 as atrophic gastritis, were enrolled. Control samples were obtained from 15 healthy H. pylori-negative volunteers. The extent of atrophic change of the gastric mucosa was assessed endoscopically. Body weight was measured and blood was collected before and 12 weeks after H. pylori eradication therapy. Blood samples were taken between 8 and 10 AM after an overnight fast.

Plasma ghrelin levels were significantly lower in H. pylori-positive patients than in H. pylori-negative patients. In particular, plasma active ghrelin levels were significantly lower in patients with gastritis compared with patients with peptic ulcer. Plasma ghrelin levels decreased after H. pylori eradication in both peptic ulcer and gastritis patients, while plasma leptin levels increased only in peptic ulcer patients. Plasma leptin levels and BMI were positively correlated, and active ghrelin levels and atrophic pattern were weakly negatively correlated in peptic ulcer patients.

H. pylori infection and eradication therapy may affect circulating ghrelin/leptin levels. This finding suggests a relationship between gastric mucosal injury induced by H. pylori infection and changes in plasma ghrelin and leptin levels.

• Eradication
• Helicobacter pylori
• Plasma Ghrelin and Leptin

• Dyspepsia
• Ghrelin
• Helicobacter pylori

• Infection
• obesity

• Cardiometabolic risk factors
• Diabetes mellitus, type 2
• Gastric inflammation
• Helicobacter pylori infection
• Pepsinogens

• Adult
• Appetite/physiology
• Body Mass Index
• Eating/physiology
• Female
• Gastrointestinal Hormones/metabolism
• Helicobacter Infections/complications
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter pylori/pathogenicity
• Humans
• Islet Amyloid Polypeptide/metabolism
• Malaysia
• Male
• Pancreatic Polypeptide/metabolism
• Peptide YY/metabolism
• Young Adult

Ghrelin, the ligand of growth hormone secretagogue receptor 1a, takes part in several functions of the digestive system, including regulation of appetite, energy homeostasis, gastric acid secretion and motility. Ghrelin has also immunoregulatory properties and is supposed to inhibit some inflammatory pathways that can mediate gastric damage. Interestingly, ghrelin synthesis is reduced in the gastric mucosa of patients with Helicobacter pylori (H. pylori) infection, a worldwide condition inducing a T helper (Th)1/Th17 cell response-driven gastritis, which may evolve towards gastric atrophy and cancer. In this article, we review the available data on the expression of ghrelin in H. pylori infection and discuss how the defective ghrelin synthesis may contribute to sustain the ongoing inflammatory response in this disease.

• Gastritis
• Ghrelin
• Helicobacter pylori
• T helper 1 cells

• Animals
• Gastric Mucosa/metabolism
• Gastritis/immunology
• Gastritis/metabolism
• Gastritis/microbiology
• Ghrelin/metabolism
• Helicobacter Infections/immunology
• Helicobacter Infections/metabolism
• Helicobacter Infections/microbiology
• Helicobacter pylori/metabolism
• Helicobacter pylori/pathogenicity
• Humans
• Inflammation Mediators/metabolism
• Signal Transduction
• Stomach/microbiology
• T-Lymphocytes, Helper-Inducer/immunology
• T-Lymphocytes, Helper-Inducer/metabolism
• T-Lymphocytes, Helper-Inducer/microbiology

The present review summarizes the prevalence and active clinical problems in obese patients with Helicobacter pylori (H. pylori) infection, as well as the outcomes after bariatric surgery in this patient population. The involvement of H. pylori in the pathophysiology of obesity is still debated. It may be that the infection is protective against obesity, because of the gastritis-induced decrease in production and secretion of the orexigenic hormone ghrelin. However, recent epidemiological studies have failed to show an association between H. pylori infection and reduced body mass index. H. pylori infection might represent a limiting factor in the access to bariatric bypass surgery, even if high-quality evidence indicating the advantages of preoperative H. pylori screening and eradication is lacking. The clinical management of infection is complicated by the lower eradication rates with standard therapeutic regimens reported in obese patients than in the normal-weight population. Prospective clinical studies to ameliorate both H. pylori eradication rates and control the clinical outcomes of H. pylori infection after different bariatric procedures are warranted.

• Helicobacter pylori
• Obesity
• Bariatric surgery
• Ghrelin
• Antibiotic resistance

• Bariatric Surgery/adverse effects
• Body Mass Index
• Helicobacter Infections/diagnosis
• Helicobacter Infections/drug therapy
• Helicobacter Infections/epidemiology
• Helicobacter Infections/microbiology
• Helicobacter pylori/pathogenicity
• Humans
• Obesity/diagnosis
• Obesity/epidemiology
• Obesity/physiopathology
• Obesity/surgery
• Prevalence
• Risk Factors
• Treatment Outcome

• CD
• CVID
• Common variable immunodeficiency
• Crohn disease
• IBD
• Immunity
• Inflammatory bowel disease
• SCFA
• Short-chain fatty acid
• TLR
• Toll-like receptor
• gut microbiota
• immunodeficiency
• intestinal lipid metabolism

Functional dyspepsia (FD) is one of the most common clinical functional gastrointestinal disorders. As a chronic, relapsing and remitting disorder, FD not only significantly affects the quality of life of patients but also causes very high medical expenses. However, the specific pathogenesis of FD has always been a big problem for gastroenterologists. Recently, motility abnormalities, visceral hypersensitivity, psychosocial factors, Helicobacter pylori, genetic factors, excessive gastric acid secretion, environment, diet, and lifestyle have been proposed to explain the pathogenesis of FD, of which the brain-gut axis, autonomic nervous system , gastrointestinal hormones may play an important role. In this paper, we review the recent progress in the pathogenesis of FD.

• Functional dyspepsia
• Pathogenesis

Functional dyspepsia is one of the most common clinical functional gastrointestinal disorders. Currently, many pathogenic factors have been proposed to explain the pathogenesis of functional dyspepsia. Although the relationship between Helicobacter pylori (H. pylori) infection and functional dyspepsia has been studied extensively, the results obtained are contradictory. In recent years, the better understanding of functional dyspepsia and several revisions of the Roman standards have led to the revelation of shortcomings of previous studies. In this paper we discuss the relationship between H. pylori infection and functional dyspepsia.

• Dyspepsia
• Functional dyspepsia
• Helicobacter pylori

Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHSR). Upon binding to its receptor, Ghrelin can produce a variety of biological effects, such as promoting the release of growth hormone and maintaining energy balance. Besides, it also promotes gastrointestinal motility, increases gastric acid secretion, and is involved in the genesis of tumors. This article reviews the role of Ghrelin in gastrointestinal system disease.

• Ghrelin
• Gastrointestinal motility
• Gastric acid secretion
• Protection of gastric mucosa
• Gastrointestinal tumor

In a cohort of 1,863 Filipinos, diarrhea, fever, and unsanitary conditions in infancy were associated with a decreased body mass index in adulthood; upper respiratory tract infection was associated with an increased body mass index. These finding support the hypothesis that infections early in life play a role in body habitus in adulthood.

AIM: To compare ghrelin levels in plasma and gastric mucosa before and after Helicobacter pylori (H. pylori) treatment in children with H. pylori-associated functional dyspepsia.

METHODS: Children with H. pylori-associated functional dyspepsia were enrolled in this study. H. pylori infection was confirmed by positive bacterial culture results. All of the children received triple H. pylori eradication therapy (a 2 wk course of omeprazole, amoxicillin, and clarithromycin). The children were divided into two groups based on the success of the H. pylori treatment: group 1 (eradicated) - patients who had a negative 13C-urea breath test 2 mo after the end of therapy; and group 2 (non-eradicated) - patients who had a positive 13C-urea breath test. Plasma ghrelin, gastric ghrelin mRNA, and the body mass index were evaluated in both groups before and after the H. pylori treatment. The plasma ghrelin levels were measured by a radioimmunoassay. The expression of gastric ghrelin mRNA was determined by real-time reverse transcription polymerase chain reaction.

RESULTS: A total of 50 children with H. pylori-associated functional dyspepsia were treated with triple H. pylori eradication therapy. The mean age of the children was 5.52 ± 0.83 years, and there were 28 males and 22 females. Among the 50 H. pylori-positive children, 30 successfully achieved eradication, and 20 did not. The mean plasma ghrelin levels of group 1 were 22.17 ± 1.73 ng/L and 26.59 ± 2.05 ng/L before and after the treatment, respectively, which was a significant increase (P = 0.001). However, the mean plasma ghrelin level of group 2 before and after the H. pylori treatment was 21.34 ± 2.40 ng/L and 22.24 ± 2.10 ng/L (P = 0.785). The plasma ghrelin levels increased substantially after treatment in group 1 but showed only minor changes in group 2. Similarly, the gastric ghrelin mRNA expression in group 1 before treatment was 2.84 ± 0.08. After treatment, the level was 3.11 ± 0.65, which was significantly different (P = 0.023). The gastric ghrelin mRNA expression in group 2 did not change significantly during the treatment (2.82 ± 0.44 vs 2.79 ± 0.31, P = 0.875). The plasma ghrelin and gastric ghrelin mRNA levels in group 1 increased substantially after the treatment but did not do so in group 2. In addition, the body mass index the two groups did not differ significantly 2 mo before and after the H. pylori treatment.

CONCLUSION: H. pylori eradication increases the plasma and tissue ghrelin levels in children with H. pylori-associated functional dyspepsia.

• Helicobacter pylori
• Functional dyspepsia
• Ghrelin
• Eradication
• Children

A two-year, prospective, nationwide multicenter study was undertaken to evaluate the effect of Helicobacter pylori eradication on the development of reflux esophagitis (RE) and gastroesophageal reflux disease (GERD) symptoms in the Korean population.

In total, 1,489 subjects without RE were enrolled at the outpatient clinics of 12 tertiary hospitals nationwide, and 452 subjects underwent follow-up (F/U) for 2 years to evaluate the development of RE and GERD symptoms.

RE was found in 33 subjects (7.3% of 452 subjects) and 14 subjects (7.3% of 192 subjects) during the first and second year of F/U, respectively. H. pylori status was not associated with the development of RE. RE was found in six (9.0%) of 67 H. pylori-negative patients, in 26 (11.2%) of 233 eradicated subjects and in eight (7.0%) of 114 noneradicated subjects (p=0.532). Multivariate analysis showed that age ≥60 years (odds ratio [OR], 7.11; 95% confidence interval [CI], 1.92 to 26.41), alcohol consumption (OR, 4.43; 95% CI, 1.03 to 19.19) and F/U cholesterol levels ≥200 mg/dL (OR, 5.03; 95% CI, 1.32 to 19.17) were significant risk factors for the development of RE. There was no significant difference in the development of GERD symptoms or weight according to H. pylori status during the 2-year F/U.

Eradication of H. pylori did not affect the development of reflux esophagitis or GERD symptoms among patients in outpatient gastroenterology clinics in South Korea.

• Eradication
• Helicobacter pylori
• Reux esophagitis
• Symptoms

Functional dyspepsia is a group of disorders featuring symptoms believed to be derived from the stomach and duodenum such as upper abdominal discomfort, pain, postprandial fullness and early satiety. A key diagnostic requisite is the absence of organic, metabolic, or systemic disorders to explain "dyspeptic symptoms." Therefore, when peptic ulcer diseases (including scars), erosive esophagitis and upper gastrointestinal malignancies are found at endoscopic examinations, the diagnosis of functional dyspepsia is excluded. One notable exception, however, is Helicobacter pylori infection. According to the Rome III definition, H. pylori infection is included in functional dyspepsia. This is an obvious deviation from the diagnostic principle of functional dyspepsia, since H. pylori infection is a definite cause of mucosal inflammation, which affects a number of important gastric physiologies such as acid secretion, gastric endocrine function and motility. The chronic persistent nature of infection also results in more dramatic mucosal changes such as atrophy or intestinal metaplasia, the presence of which in the esophagus (Barrett's esophagus) precludes the diagnosis of functional dyspepsia. Since careful endoscopic examination can diagnose reliably H. pylori infection not only in Japan but also in Western contries, it is now feasible and more logical to exclude patients with chronic gastritis caused by H. pylori infection as having dyspeptic symptoms. It is time to establish the Asian consensus to declare that H. pylori infection should be separated from functional dyspepsia.

• Dyspepsia
• Functional dyspepsia
• Gastric acid
• Helicobacter pylori
• Ulcer

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.

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.

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.

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.

Ghrelin is predominantly produced by the gastric enteroendocrine cell compartment and is octanoylated by the recently discovered ghrelin o-acyltransferase (GOAT) before secretion into the bloodstream. This octanoylation is essential for many of the biological properties of ghrelin including appetite stimulation and anti-inflammatory properties as only the acylated form of ghrelin binds to the ghrelin receptor, the growth hormone secretagogue receptor (GHS-R). Given the gastric location of ghrelin production, it is perhaps not surprising that insult to the gastric mucosa affects circulating ghrelin levels in humans. Helicobacter pylori (H. pylori) infects more than fifty percent of the world’s population and once established within the gastric mucosa, can persist for life. Infection is associated with chronic gastritis, gastric atrophy and ulceration, reduced appetite and a lower body mass index (BMI). The large majority of studies investigating levels of circulating ghrelin and ghrelin expression in the stomach in patients with H. pylori infection indicate that the bacterium has a negative impact on ghrelin production and/or secretion. Eradication of infection restores ghrelin, improves appetite and increases BMI in some studies, however, a causative relationship between H. pylori-associated serum ghrelin decline and food intake and obesity has not been established. Most studies measure total ghrelin in the circulation although the measurement of the ratio of acyl/total ghrelin gives a clearer indication that the ghrelin acylation process is altered during infection and atrophy. GOAT is essential for the production of biologically-active, acyl ghrelin and the impact of H. pylori on GOAT expression and activity will be highly informative in the future.

• Appetite
• Ghrelin
• Ghrelin o-acyltransferase
• Helicobacter pylori
• Infection
• Inflammation
• Obesity

The nature of the association between ghrelin, an orexigenic hormone produced mainly in the stomach, and Helicobacter pylori (H pylori), a bacterium that colonises the stomach, is still controversial. We examined available evidence to determine whether an association exists between the two; and if one exists, in what direction.

We reviewed original English language studies on humans reporting circulating ghrelin levels in H pylori infected and un-infected participants; and circulating ghrelin levels before and after H pylori eradication. Meta-analyses were conducted for eligible studies by combining study specific estimates using the inverse variance method with weighted average for continuous outcomes in a random effects model.

Seventeen out of 27 papers that reported ghrelin levels in H pylori positive and negative subjects found lower circulating ghrelin levels in H pylori positive subjects; while 10 found no difference. A meta-analysis of 19 studies with a total of 1801 participants showed a significantly higher circulating ghrelin concentration in H pylori negative participants than in H pylori positive participants (Effect estimate (95%CI) = -0.48 (-0.60, -0.36)). However, eradicating H pylori did not have any significant effect on circulating ghrelin levels (Effect estimate (95% CI) = 0.08 (-0.33, 0.16); Test for overall effect: Z = 0.67 (P = 0.5)).

We conclude that circulating ghrelin levels are lower in H pylori infected people compared to those not infected; but the relationship between circulating ghrelin and eradication of H pylori is more complex.

AIM: To investigate the level of gastric ghrelin in stomach mucosa of dyspeptic patients in relation to Helicobacter pylori (H pylori) infection, bacterial cytotoxicity, topography and gender.

METHODS: The study comprised 40 premenopausal women (19 H pylori positive) and 48 men (17 H pylori positive) with functional dyspepsia. All gastric biopsy specimens revealed normal mucosa or non-atrophic gastritis. Gastric ghrelin concentration was determined by Enzyme linked immunosorbent assay. The cagA and vacA strains of bacterial DNA were identified by multiplex polymerase chain reaction.

RESULTS: In general, infection with H pylori caused an increase in gastric ghrelin level regardless of gender and stomach topography. Significantly more hormone was present in both, non-infected and H pylori positive female samples, as compared to males. The distribution of bacterial strains showed cagA(+) vacA s1m1 and cagA(-) vacA s2m2 genotypes as the most common infections in the studied population. A tendency to higher ghrelin levels was observed in less cytotoxic (cagA negative) strain-containing specimens from the antrum and corpus of both gender groups (without statistical significance).

CONCLUSION: An increase in gastric ghrelin levels at the stage of non-atrophic gastritis in H pylori positive patients, especially in those infected with cagA(-) strains, can exert a gastroprotective effect.

• Dyspepsia
• Gastric ghrelin
• Helicobacter pylori
• Gender

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. Ghrelin also plays an essential role in the mechanism of gastric mucosal defense. Thus, it is important to clarify which diseases primarily influence changes in plasma ghrelin concentrations. Helicobacter pylori (H pylori) infection is involved in the pathogenesis of gastritis, gastric and duodenal ulcer, gastric carcinoma, and mucosa-associated lymphoid tissue lymphoma. H pylori eradication is related to body weight change. Compared, H pylori infected and negative subjects with normal body mass index, plasma ghrelin concentration, gastric ghrelin mRNA, and the number of ghrelin producing cells in gastric mucosa are significantly lower in H pylori infected subjects than in H pylori-negative controls. Plasma ghrelin concentration decreases with the progression of gastric atrophy. Impaired gastric ghrelin production in association with atrophic gastritis induced by H pylori infection accounts for the decrease in plasma ghrelin concentration. However, the ratio of plasma acylated ghrelin to total ghrelin levels is higher in patients with chronic atrophic gastritis than in healthy subjects. This may result from the compensatory increase in plasma active ghrelin concentration in response to gastric atrophy. After H pylori eradication, gastric preproghrelin mRNA expression is increased nearly 4-fold in most cases. However, changes in plasma ghrelin concentrations before and after H pylori cure are not associated with the gastric ghrelin production. Plasma ghrelin changes are inversely correlated with both body weight change and initial plasma ghrelin levels.

• Ghrelin
• Helicobacter pylori
• Eradication
• Body weight
• Leptin