Association of baseline plasma des-acyl ghrelin level with the response to rikkunshito in patients with functional dyspepsia.

BACKGROUND AND AIM: We recently conducted a randomized placebo-controlled trial on the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for the treatment of functional dyspepsia (FD). The present post-hoc study aimed to evaluate the differences in clinical characteristics between responders and non-responders among FD patients who received rikkunshito for 8 weeks. METHODS: Rikkunshito responders were defined by using a global patient assessment. Candidate predictors included age, gender, smoking, alcohol consumption, body mass index, comorbidity, Helicobacter pylori infection, plasma levels of acyl ghrelin and des-acyl ghrelin, severity of dyspeptic symptoms, FD subgroup, previous medication, and the type of recruiting institution (clinic or hospital). We calculated hazard ratios (HRs) by using Cox regression analysis with the factors that were indicated to be associated with responders. RESULTS: We assigned 83 and 42 patients to responder and non-responder categories, respectively. Lack of alcohol consumption (HR, 2.04; 95% confidence interval, 1.08-3.88) and low plasma des-acyl ghrelin levels (< 177 fmol/mL; HR, 2.42; 95% confidence interval, 1.24-4.73) were significantly associated with the efficacy of rikkunshito. Lack of alcohol consumption was associated with the efficacy of rikkunshito especially among H. pylori-infected participants. On the other hand, the low plasma des-acyl ghrelin was associated with the efficacy of rikkunshito especially among H. pylori-negative participants. CONCLUSIONS: A low baseline level of plasma des-acyl ghrelin was associated with an increased treatment efficacy of rikkunshito against FD. Lack of alcohol consumption was also clinically useful for predicting the response to rikkunshito.

Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine.

AIM: To investigate the effect of a fat rich diet on non-steroidal anti-inflammatory drug (NSAID)-induced mucosal damage in the murine small intestine. METHODS: C57BL6 mice were fed 4 types of diets with or without indomethacin. One group was fed standard laboratory chow. The other groups were fed a fat diet consisting of 8% w/w fat, beef tallow (rich in SFA), fish oil, (rich in omega-3 PUFA), or safflower oil (rich in omega-6 PUFA). Indomethacin (3 mg/kg) was injected intraperitoneally from day 8 to day 10. On day 11, intestines and adhesions to submucosal microvessels were examined. RESULTS: In the indomethacin-treated groups, mucosal damage was exacerbated by diets containing beef tallow and fish oil, and was accompanied by leukocyte infiltration (P < 0.05). The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet (P < 0.05). Indomethacin increased monocyte and platelet migration to the intestinal mucosa, whereas safflower oil significantly decreased monocyte and platelet recruitment (P < 0.05). CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte infiltration. Importantly, a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis.

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.

Effect of dietary fat on intestinal inflammatory diseases.

Dietary fat has multiple roles on human health, and some dietary fat is used to treat organic diseases because of its anti-inflammatory effect. It is commonly accepted that omega-3 polyunsaturated fatty acid (PUFA) is beneficial on ischemic heart disease or rheumatic arthritis. On the contrary, effect of omega-3-PUFA on Crohn's disease remained controversial. That effect of omega-3 PUFA differs according to the location of inflamed intestine was hypothesized. To elucidate this hypothesis, to investigate the role of dietary fat on disease activity in different kind of murine models of intestinal inflammatory diseases was planned. The effect of omega-3 PUFA on small intestinal Crohn's disease model and large intestinal Crohn's disease model of mice. Chronic colitis model C57BL/6 mice received two cycles of dextran sodium sulfate solution treatment to induce chronic colitis. Feeding of omega-3 fat-rich diets exacerbated colitis with decrease in adiponectin expression. Chronic small intestinal inflammation model: SAMP1/Yit mice showed remarkable inflammation of the terminal ileum spontaneously. Feeding of omega-3 fat-rich diets for 16 weeks significantly ameliorated the inflammation of the terminal ileum. Enhanced infiltration of leukocytes and expression of mucosal addressin cell adhesion molecule-1 in intestinal mucosa was significantly decreased by omega-3 fat-rich diets treatment. Omega-3 PUFA has dual role, pro-/anti-inflammatory, on intestinal inflammatory diseases. The role of omega-3 fat and the potential for immunonutrition in inflammatory conditions of the gastrointestinal tract will be discussed.

Dietary lipids and sweeteners regulate glucagon-like peptide-2 secretion.

Glucagon-like peptide-2 (GLP-2) is a potent intestinal growth factor derived from enteroendocrine L cells. Although food intake is known to increase GLP-2 secretion, its regulatory mechanisms are largely unknown as a result of its very short half-life in venules. The aims of this study were to compare the effects of luminal nutrients on the stimulation of GLP-2 secretion in vivo using lymph samples and to clarify the involvement of the sweet taste receptor in this process in vitro. Lymph samples were collected from the thoracic duct after bolus administration of dietary lipids or sweetening agents into the duodenum of rats. Human enteroendocrine NCI-H716 cells were also used to compare the effects of various nutrients on GLP-2 secretion. GLP-2 concentrations were measured by ELISA in vivo and in vitro. GLP-2 secretion was enhanced by polyunsaturated fatty acid- and monounsaturated fatty acid-rich dietary oils, dietary carbohydrates, and some kinds of sweeteners in rats; this effect was reproduced in NCI-H716 cells using α-linolenic acid (αLA), glucose, and sweeteners. GLP-2 secretion induced by sweetening agents was inhibited by lactisole, a sweetness-antagonizing inhibitor of T1R3. In contrast, lactisole was unable to inhibit GLP-2 secretion induced by αLA alone. Our results suggested that fatty acid- and sweetener-induced GLP-2 secretion may be mediated by two different pathways, with the sweet taste receptor involved in the regulation of the latter.

Diagnosis and treatment of functional gastrointestinal disorders in the Asia-Pacific region: a survey of current practices.

BACKGROUND AND AIMS: Functional gastrointestinal disorders (FGIDs), namely functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common disorders important to public health in the Asia-Pacific region. Our objectives were to determine the current practices in diagnosis and management of these disorders in the Asia-Pacific region. METHODS: Forty-three physicians and researchers in FGID who attended the first Asian Pacific Topic Conference at Tokyo in November 2010 were invited to answer a questionnaire. Twenty-three Japanese doctors and twenty doctors from other Asia-Pacific Societies answered the questionnaire, which consisted of 60 multiple-choice questions concerning physician's preferences in diagnosis and management of FGIDs. RESULTS: Overall, there were similarities in diagnostic approach, such as differential diagnosis, exclusion of organic diseases, psychophysiological assessment, medical advice or medication with psychological drugs, not only among different Asia-Pacific region but also between FD and IBS. Several notable differences were seen. For example, general practitioners did not commonly use the term FD or diagnose FD by themselves, while the term IBS was widely used and frequently diagnosed. Sub-categorization was more common in IBS than FD. There was also a difference between Japan and other Asia-Pacific region; upper GI endoscopy and blood examination were more common in Japan, while eradication of Helicobacter pylori was more frequently done in other countries. Anti-secretory drugs for FD and mild laxatives or anti-diarrheal drug for IBS were frequently used, and prokinetics were used for all patients with FD or IBS. Interestingly, drugs developed in Japan and Chinese herbal medicines were more frequently prescribed in Japan. CONCLUSION: Information obtained in this survey is useful for understanding the most common clinical approaches for FGIDs in the Asia-Pacific region.

Lemon grass (Cymbopogon citratus) ameliorates murine spontaneous ileitis by decreasing lymphocyte recruitment to the inflamed intestine.

OBJECTIVE: Aberrant leukocyte migration has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Lemon grass is a natural herb that contains citral, which suppresses lymphocyte expression of gut homing molecules by inhibiting retinoic acid formation. We therefore hypothesized that lemon grass intake could ameliorate excess migration of leukocytes to the inflamed intestine in chronic ileitis. METHODS: Migration of fluorescence-labeled T cells to microvessels in the ileal mucosa of SAMP1/Yit mice was monitored using intravital microscopy. In some mice, lemon grass solution was administered for two weeks. For evaluation of the effects on chronic ileitis, mice were treated with lemon grass for 26 weeks. RESULTS: Surface expression of beta7 and CCR9 on T lymphocytes was stronger in SAMP1/Yit mice than in AKR/J mice. Lemon grass treatment attenuated the surface expression of beta7-integrin and CCR9. The number of adherent lymphocytes to microvessels in chronic inflamed ileum was significantly few when lymphocytes were isolated from lemon grass treated mice. Long-term lemon grass treatment improved ileitis in SAMP1/Yit mice, which was assessed by body weight, histological changes and the infiltration of beta7-positive cells. CONCLUSION: Lemon grass ameliorated ileitis through decreasing lymphocyte migration by inhibiting beta7-expression, suggesting its therapeutic usefulness for IBD.

An antioxidant resveratrol significantly enhanced replication of hepatitis C virus.

AIM: To elucidate the effect of antioxidants, resveratrol (RVT) and astaxanthin (AXN), on hepatitis C virus (HCV) replication. METHODS: We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6. RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses. AXN is also a strong antioxidant. The replication of HCV RNA was assessed by the luciferase reporter assay. An additive effect of antioxidants on antiviral effects of interferon (IFN) and ribavirin (RBV) was investigated. RESULTS: This is the first report to investigate the effect of RVT and AXN on HCV replication. In contrast to other reported viruses, RVT significantly enhanced HCV RNA replication. Vitamin E also enhanced HCV RNA replication as reported previously, although AXN did not affect replication. IFN and RBV significantly reduced HCV RNA replication, but these effects were dose-dependently hampered and attenuated by the addition of RVT. AXN did not affect antiviral effects of IFN or RBV. CONCLUSION: These results suggested that RVT is not suitable as an antioxidant therapy for chronic hepatitis C.

Omega-3 fatty acids exacerbate DSS-induced colitis through decreased adiponectin in colonic subepithelial myofibroblasts.

BACKGROUND: Although the immunoregulatory effects of omega-3 fatty acid and adiponectin have been postulated, their role in intestinal inflammation is controversial. The aim of this study was to determine whether dietary fat intake influences activity of colonic inflammation through modulating this system. METHODS: C57BL/6 mice received dextran sulfate sodium for induction of colitis. Mice were fed a control diet, omega-3 fat-rich diet, omega-6 fat-rich diet, or saturated fat-rich diet. Some mice were administered a peroxisome proliferator activated receptor-gamma; agonist, pioglitazone. Messenger RNA expression of adiponectin and its receptors were analyzed. Adiponectin expression in colonic mucosa of ulcerative colitis patients was also analyzed. RESULTS: The receptors for adiponectin were found to be ubiquitously expressed in epithelial cells, intraepithelial lymphocytes, lamina proprial mononuclear cells, and subepithelial myofibroblasts from colonic tissue, but adiponectin was only expressed in myofibroblasts. Induction of colitis significantly decreased the expression of adiponectin in colonic mucosa. The omega-3 fat diet group, but not the other fat diet groups, showed exacerbated colitis with a further decrease of adiponectin expression. Pioglitazone treatment ameliorated the level of decrease in adiponectin expression and improved colonic inflammation induced by the omega-3 fat-rich diet. In patients with ulcerative colitis, the expression level of adiponectin in colonic mucosa was also decreased compared with that in control mucosa. CONCLUSIONS: Adiponectin was found to be expressed in myofibroblasts. Adiponectin expression was significantly suppressed by induction of colitis, and aggravation of colitis after exposure to omega-3 fat may be due to a further decrease in the expression level of adiponectin.

Ameliorating effects of compounds derived from Salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion.

Ischemia and reperfusion (I/R) exerts multiple insults in microcirculation, frequently accompanied by endothelial cell injury, enhanced adhesion of leukocytes, macromolecular efflux, production of oxygen free radicals, and mast cell degranulation. Since the microcirculatory disturbance results in injury of organ involved, protection of organ after I/R is of great importance in clinic. Salvia miltiorrhiza root has long been used in Asian countries for clinical treatment of various microcirculatory disturbance-related diseases. This herbal drug contains many active water-soluble compounds, including protocatechuic aldehyde (PAl), 3,4-dihydroxyphenyl lactic acid (DLA) and salvianolic acid B (SalB). These compounds, as well as water-soluble fraction of S. miltiorrhiza root extract (SMRE), have an ability to scavenge peroxides and are able to inhibit the expression of adhesion molecules in vascular endothelium and leukocytes. Moreover, lipophilic compounds of SMRE also prevent the development of vascular damage; NADPH oxidase and platelet aggregation are inhibited by tanshinone IIA and tanshinone IIB, respectively, and the mast cell degranulation is blunted by cryptotanshinone and 15,16-dihydrotanshinone I. Thus, the water-soluble and lipophilic compounds of SMRE appear to improve the I/R-induced vascular damage multifactorially and synergically. This review will summarize the ameliorating effect of compounds derived from SMRE on microcirculatory disturbance and target organ injury after I/R and will provide a new perspective on remedy with multiple drugs.

Butter feeding enhances TNF-alpha production from macrophages and lymphocyte adherence in murine small intestinal microvessels.

BACKGROUND AND AIM: Dietary fat is known to modulate immune functions. Intake of an animal fat-rich diet has been linked to increased risk of inflammation; however, little is known about how animal fat ingestion directly affects intestinal immune function. The objective of this study was to assess the effect of butter feeding on lymphocyte migration in intestinal mucosa and the changes in adhesion molecules and cytokines involved in this effect. METHODS: T-lymphocytes isolated from the spleen were fluorescence-labeled and injected into recipient mice. Butter was administered into the duodenum, and villus microvessels of the small intestinal mucosa were observed under an intravital microscope. mRNA expression of adhesion molecules and cytokines in the intestinal mucosa were determined by quantitative PCR. The effect of butter feeding on tumor necrosis factor (TNF)-alpha mRNA expression of intestinal macrophages was also determined. RESULTS: Intraluminal butter administration significantly increased lymphocyte adherence to intestinal microvessels accompanied by increases in expression levels of adhesion molecules ICAM-1, MAdCAM-1 and VCAM-1. This accumulation was significantly attenuated by anti-MAdCAM-1 and anti-ICAM-1 antibodies. Butter administration significantly increased TNF-alpha in the lamina proprial macrophages but not interleukin-6. Anti-TNF-alpha treatment attenuated the enhanced expression of adhesion molecules induced by butter administration. CONCLUSION: T-lymphocyte adherence to microvessels of the small intestinal mucosa was significantly enhanced after butter ingestion. This enhancement is due to increase in expression levels of adhesion molecules of the intestinal mucosa, which is mediated by TNF-alpha from macrophages in the intestinal lamina propria.

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery.

AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITC-albumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo, all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.

Effect of risedronate on high-dose corticosteroid-induced bone loss in patients with glomerular disease.

BACKGROUND: Corticosteroids are often used for the treatment of glomerular diseases. We examined whether bisphosphonate or vitamin D3 has beneficial effects on bone mineral density (BMD) in patients with glomerular diseases being treated with high-dose corticosteroids, including pulse therapy. METHODS: Thirty-eight patients (19 men and 19 women, aged 42 +/- 16 years) were randomized into three groups: bisphosphonate alone (risedronate 2.5 mg/day, group R, n = 12), vitamin D3 alone (alfacalcidol 0.5 mug/day, group A, n = 15) and the combination of both agents (group R+A, n = 11). BMD at the lumbar spine was measured before and 12 months after treatment. The biochemical parameters of bone metabolism were assessed before and 3, 6 and 12 months after treatment. RESULTS: In group R+A, BMD was significantly increased (+2.0%), whereas BMD was significantly decreased in group A (-5.6%). The BMD in group R did not show a significant change. In patients treated with steroid-pulse, BMD was decreased in groups R and A. In group R+A, BMD was significantly increased (+2.1%). Serum osteocalcin and alkaline phosphatase levels, markers of bone formation, were significantly decreased in all groups. Urinary crosslinked N-telopeptide of type I collagen (NTx) levels, a marker of bone resorption, were decreased in groups R and R+A. In patients with decreased BMD, the urinary NTx levels at baseline were significantly higher than the patients with increased BMD. CONCLUSIONS: Bisphosphonate might be beneficial for the prevention of steroid-induced bone loss in patients with glomerular diseases compared with vitamin D3. The combined therapy may be more effective, especially in patients treated with high-dose corticosteroids, including pulse therapy. A high urinary NTx level before receiving corticosteroids might be a predictive marker of the loss of BMD.

Jumbo biopsy is useful for the diagnosis of colonic prolapsing mucosal polyps with diverticulosis.

We report here a case of multiple prolapsing mucosal polyps with diverticulosis in the sigmoid colon. A 52-year-old man was admitted to our hospital because of bloody diarrhea. Colonoscopy and barium enema showed multiple diverticula, markedly thickened mucosal folds and polypoid lesions with mucus on the top of them in the sigmoid colon. Endoscopic ultrasonography showed thickening of the mucosal and submucosal layers. Several endoscopic biopsy specimens were taken from the polypoid lesions. Histological examination revealed only chronic inflammatory cell infiltration. In order to obtain a definite diagnosis, we performed endoscopic jumbo biopsy for the polypoid lesions after obtaining informed consent. Histological examination revealed marked lymphocyte infiltration, hemosiderin deposits and fibromuscular obliteration in the lamina propria, features similar to those of mucosal prolapsing syndrome. After anti-diarrhetic treatment, clinical findings were improved. Thus, jumbo biopsy is useful for diagnosis and treatment of prolapsing mucosal polyps.

Attenuating effect of Myakuryu on mesenteric microcirculatory disorders induced by ischemia and reperfusion.

Myakuryu (MR) is a newly developed herbal medicine composing Crataegue oinnatifida bge (COB), Panax notoginseng (PN) and Ginkyo biloba (GB). To examine the effectiveness of MR, we investigated its effects on rat mesenteric microcirculatory injury induced by ischemia/reperfusion (I/R). The mesenteric microcirculation of ileocecal portion of a male Wistar rat was observed through an inverted-type intravital microscope assisted with a charge-coupled devise (CCD) camera. Mesenteric I/R was conducted by a ligation of the mesenteric artery and vein (10 min) and subsequent release of the occlusion. We measured venular diameter, the number of adherent leukocytes, dihydrorhodamine 123 (DHR) fluorescence as an indicator of oxidative stress and mast cell degranulation, with or without MR extract (0.4 g/kg b.w.) via an orogastric tube 1 hr before I/R. The diameters of the observed mesenteric venules were not changed after the mesenteric I/R. MR had no effect on venular diameter. The leukocytes adhering to the post-capillary venular walls started just after reperfusion, and increased thereafter. The increased number of adherent leukocytes was significantly reduced by treatment with MR. DHR fluorescence ratio was significantly increased along the venular wall. MR attenuated the increased oxidation. The mesenteric I/R induced mast cell degranulation. The increase in mast cell degranulation was inhibited by MR. In conclusion, oral administration of MR attenuates I/R-induced microvascular damages in rat mesentery. MR has a therapeutic potential for prevention of I/R-related microvascular injury.

Combination therapy with tumor-lysate pulsed dendritic cells and antiangiogenic drug TNP-470 for mouse pancreatic cancer.

Most cases of pancreatic cancer are inoperable when diagnosed. Since immunotherapy and antiangiogenic therapy have been reported to be promising for pancreatic cancer, we examined whether the combination of immunotherapy with dendritic cells (DCs) and the antiangiogenic drug TNP-470 induces tumor regression. Syngeneic mouse pancreatic adenocarcinoma cells were orthotopically inoculated into C57/BL6 mice. DCs with or without tumor lysate (TL) were administered i.p. at 4 and 5 weeks. TNP-470 was injected s.c. into tumor-bearing mice every other day from 4 weeks to 6 weeks. We compared anticancer effects in 6 groups: NT (no treatment), DC/TL- (DCs without TL), DC/TL+ (DCs pulsed with TL), TNP (TNP-470 alone), DC/TL-TNP (DC/TL- plus TNP-470) and DC/TL+TNP (DC/TL+ plus TNP-470). We measured tumor volume, mean vascular density (MVD) and vessel diameter by FITC-dextran using an intravital microscope; degrees of proliferation and apoptosis of cancer cells by PCNA and TUNEL; infiltrating lymphocytes and expression levels of VEGF and MMP-9 by immunohistochemistry and immunoblotting. Tumor volume and MVD were significantly suppressed in the treatment groups with prolonged survival rate, especially in the DC/TL+TNP group. There were no significant differences in apoptosis among the 6 groups except DC/TL+. The number of infiltrating CD4+ cells in the DC/TL+ group was higher than that in the NT group. VEGF expression was significantly suppressed in the treatment groups containing TNP-470, and MMP-9 was also suppressed in the groups containing DC/TL+. Our data suggested that TL-pulsed DCs combined with TNP-470 induced regression of mouse pancreatic cancer, possibly through induction of immune responses and suppression of angiogenesis.

Melanoidin, a food protein-derived advanced maillard reaction product, suppresses Helicobacter pylori in vitro and in vivo.

BACKGROUND: Extracellular urease proteins located on the surface of Helicobacter pylori are gastric mucin-targeted adhesins, which play an important role in infection and colonization to the host. In this study we have determined the inhibitory activity of a variety of melanoidins, protein-derived advanced Maillard reaction products, ubiquitously found in heat-treated foods, on urease-gastric mucin adhesion. In addition, we have determined the anticolonization effect of melanoidin I, prepared by the Maillard reaction between casein and lactose, in an animal model and in human subjects infected with this bacterium. METHODS: The inhibitory activity of each compound was determined by a competitive binding assay of labeled gastric mucin to plate-immobilized urease. Melanoidin I was used in an in vivo trial using euthymic hairless mice as an infection model. Melanoidin I was consumed for 8 weeks by subjects infected with H. pylori. The [(13)C] urease breath test and H. pylori-specific antigen in the stool (HpSA) test were performed on subjects at week 0 and week 8. RESULTS: A variety of food protein-derived melanoidins strongly inhibited urease-gastric mucin adhesion in the concentration range of 10 micro g/ml to 100 micro g/ml. In particular, melanoidin I significantly (p <.05) suppressed colonization of H. pylori in mice when given for 10 weeks via the diets. Eight weeks daily intake of 3 g melanoidin I significantly (p <.05) decreased the optical density of HpSA in subjects. CONCLUSION: Foods containing protein-derived melanoidins may be an alternative to antibiotic-based therapy to prevent H. pylori that combines safety, ease of administration and efficacy.