Sigal M(1), Rothenberg ME(2), Logan CY(3), Lee JY(4), Honaker RW(5), Cooper
RL(5), Passarelli B(6), Camorlinga M(7), Bouley DM(8), Alvarez G(9), Nusse R(3),
Torres J(7), Amieva MR(10).
Gastroenterology. 2015 Feb 25. pii: S0016-5085(15)00271-1. doi: 10.1053/j.gastro.2015.02.049. [Epub ahead of print]
BACKGROUND & AIMS: Helicobacter pylori infection is the main risk factor for gastric cancer. We characterized
the interactions of H pylori with gastric epithelial progenitor and stem cells in humans and mice and investigated how
these interactions contribute to H pylori-induced pathology.
METHODS: We used quantitative confocal microscopy and 3-dimensional reconstruction of entire gastric glands to determine the localizations of H pylori in stomach tissues from
humans and infected mice. Using lineage tracing to mark cells derived from Lgr5+ stem cells (Lgr5-eGFP-IRES-CreERT2/Rosa26-TdTomato mice) and in situ hybridization, we analyzed gastric stem cell responses to infection. Isogenic H pylori
mutants were used to determine the role of specific virulence factors in stem cell activation and pathology.
RESULTS: H pylori grow as distinct bacterial microcolonies deep in the stomach glands and interact directly with
gastric progenitor and stem cells in tissues from mice and humans. These gland-associated bacteria activate stem cells, increasing the number of stem cells, accelerating Lgr5(+) stem cell proliferation, and upregulating expression of stem cell-related genes. Mutant bacteria with defects in chemotaxis that are able to colonize the stomach surface but not the
antral glands in mice do not activate stem cells. Moreover, bacteria that are unable to inject the contact-dependent virulence factor CagA into the epithelium colonized stomach glands in mice, but did not activate stem
cells or produce hyperplasia to the same extent as wild-type H pylori.
CONCLUSIONS: H pylori colonize and manipulate the progenitor and stem cell compartments, which alters turnover
kinetics and glandular hyperplasia. Bacterial ability to alter the stem cells has important implications for
gastrointestinal stem cell biology and H pylori-induced gastric pathology.
Subhash VV(1), Ho B(1).
Microbiology. 2015 Feb 26. pii: mic.0.000066. doi: 10.1099/mic.0.000066. [Epub ahead of print]
H. pylori is a major etiological agent in the development of various gastro-duodenal diseases. Its persistence in gastric mucosa is determined by the interaction between various host, microbial
and environmental factors. The bacteria colonizes the gastric epithelium and induces activation of various chemokine
mediators, including NFKB, the master regulator of inflammation. H.pylori infection is also associated with an
increase in expression of cell cycle regulators thereby leading to mucosal cell hyper proliferation. Thus, H.pylori-associated infections manifest activation of key host response events, which inadvertently could lead to the
establishment of chronic infection and neoplastic progression. This article reviews and elaborates the current
knowledge in H. pylori induced activation of various host signaling pathways that could promote cancer development.
Special focus is placed on the inflammatory and proliferative responses that could serve as suitable biomarkers of
infection, since a sustained cell proliferation in an environment rich in inflammatory cells is characteristic in
H. pylori-associated gastric malignancies. Here, the role of ERK and WNT signaling in H. pylori-induced activation of inflammatory and proliferative responses respectively is discussed in detail. An in depth analysis
of the underlying signaling pathways and interacting partners causing alterations in these crucial host responses could
contribute to the development of successful therapeutic strategies for the prevention, management and treatment of
H. pylori infection.
这项在印度进行的研究将212例患者随机分为2组，旨在评价含环丙沙星和含克拉霉素14天序贯疗法的幽门螺杆菌根除治疗疗效。结果显示，含环丙沙星序贯疗法的根除率高于含克拉霉素序贯疗法（根除率分别为87.6% vs 76%），且两者在患者依从性和副作用方面无显著差异。
Helicobacter pylori eradication: A randomized trial.
Chaabane NB(1), Al-Adhba HS.
Indian J Gastroenterol. 2015 Feb 28. [Epub ahead of print]
BACKGROUND AND STUDY AIMS: Helicobacter pylori eradication rates with standard triple therapy have declined
to unacceptable levels. This randomized trial aimed at evaluating the efficacy of a ciprofloxacin containing sequential
regimen in the eradication of H. pylori-infected patients vs. a clarithromycin containing sequential therapy.
METHODS: A total of 212 patients were randomized into 14-day therapeutic schemes (106 patients per group): (1) clarithromycin-containing sequential therapy rabeprazole plus amoxicillin for 7 days, followed by rabeprazole plus clarithromycin
plus metronidazole for 7 days, and (2) ciprofloxacin-containing sequential therapy using ciprofloxacin instead of clarithromycin. Eradication was confirmed by stool
H. pylori antigen. Adverse effects and compliance were assessed by a questionnaire.
RESULTS: Per protocol cure rates were as follows: 87.6 % in the ciprofloxacin-containing sequential therapy and 76 % in the clarithromycin group. Intention-to-treat cure rates were as follows: 73.5 % for the ciprofloxacin group and 66 % for the clarithromycin group. No
differences in compliance or adverse effects were demonstrated among treatments.
CONCLUSION: Ciprofloxacin-containing sequential therapy is more effective and equally safe compared to a clarithromycin-containing sequential therapy.
Yilmaz I(1), Erkul E, Berber U, Kucukodaci Z, Narli G, Haholu A, Demirel D.
Eur Arch Otorhinolaryngol. 2015 Feb 27. [Epub ahead of print]
A definitive relationship between Helicobacter pylori (HP) and upper respiratory tract disorders has not been
established. In this case-control study, we investigated the relationship between HP and laryngeal carcinoma by real-time PCR method in Turkey. 74 subjects were enrolled from patients who were admitted to the Otolaryngology
Department. Formalin-fixed-paraffin-embedded tissue samples with laryngeal cancer were used and all samples were evaluated by real-time PCR method. Our study population included 72 males and 2 females with a mean age range of 62.7 years.
Helicobacter Pylori was detected in only one case. The positive case was also investigated with histopathologic
evaluation and HP immunohistochemistry. However, we could not detect HP in this case with both methods.
This study revealed that HP might not contribute to the pathogenesis of laryngeal carcinoma. A definitive relationship
between HP and upper respiratory tract disorders has not been established.
Matak P(1), Heinis M(1), Mathieu JR(1), Corriden R(2), Cuvellier S(1), Delga
S(1), Mounier R(3), Rouquette A(4), Raymond J(4), Lamarque D(5), Emile JF(5),
Nizet V(2), Touati E(6), Peyssonnaux C(7).
J Immunol. 2015 Feb 20. pii: 1401260. [Epub ahead of print]
Helicobacter pylori infection triggers chronic inflammation of the gastric mucosa that may progress to gastric cancer.
The hypoxia-inducible factors (HIFs) are the central mediators of cellular adaptation to low oxygen levels (hypoxia), but they have
emerged recently as major transcriptional regulators of immunity and inflammation. No studies have investigated
whether H. pylori affects HIF signaling in immune cells and a potential role for HIF in H. pylori-mediated gastritis. HIF-1 and HIF-2 expression was examined in human H. pylori-positive gastritis biopsies. Subsequent experiments were performed in naive and polarized bone marrow-derived macrophages from wild-type (WT) and myeloid HIF-1α-null mice (HIF-1(Δmyel)). WT and HIF-1(Δmyel) mice were inoculated with H. pylori by oral gavage and sacrificed 6 mo postinfection. HIF-1 was specifically expressed in macrophages of human H. pylori-positive gastritis biopsies. Macrophage HIF-1 strongly contributed to the induction of proinflammatory genes (IL-6, IL-1β) and inducible NO synthase in response to H. pylori. HIF-2 expression and markers of M2 macrophage differentiation were decreased in response to H. Pylori. HIF-1(Δmyel) mice inoculated with H. pylori for 6 mo presented with a similar bacterial colonization than WT mice but,
surprisingly, a global increase of inflammation, leading to a worsening of the gastritis, measured by an increased
epithelial cell proliferation. In conclusion, myeloid HIF-1 is protective in H.pylori-mediated gastritis, pointing to the complex counterbalancing roles of innate immune and inflammatory phenotypes
in driving this pathology.
6. 幽门螺杆菌毒力因子CagA 在细菌微转运系统（ibNOTs）内的转运路径
Wu H(1), Iwai N, Nakano T, Ooi Y, Ishihara S, Sano K.
Med Mol Morphol. 2015 Feb 24. [Epub ahead of print]
Helicobacter pylori (H. pylori) possesses an intrabacterial nanotransportation system (ibNoTS) for transporting CagA
and urease within the bacterial cytoplasm; this system is controlled by the extrabacterial environment.
The transportation routes of the system have not yet been studied in detail. In this study, we demonstrated by
immunoelectron microscopy that CagA localizes closely with the MreB filament in the bacterium, and MreB
polymerization inhibitor A22 obstructs ibNoTS for CagA. These findings indicate that the route of ibNoTS for
CagA is closely associated with the MreB filament. Because these phenomena were not observed in ibNoTS for
urease, the route of ibNoTS for CagA is different from that of ibNoTS for urease as previously suggested.
We propose that the route of ibNoTS for CagA is associated with the MreB filament in H. pylori.
Eradication: A Long-Term Prospective Analysis.
Suzuki S(1), Gotoda T, Suzuki H, Kono S, Iwatsuka K, Kusano C, Oda I, Sekine S,
Helicobacter. 2015 Feb 23. doi: 10.1111/hel.12218. [Epub ahead of print]
BACKGROUND: Helicobacter pylori infection causes gastric neoplasia via development of chronic atrophic gastritis
and intestinal metaplasia. The effect of H. pylori eradication on pre-existing gastric neoplasias is still controversial. The aim of this study was to use long-term observation to clarify morphologic and histologic changes in gastric adenomas following H. Pylori eradication.
MATERIALS AND METHODS: Twenty-seven patients with gastric adenomas (revised Vienna classification category 3 or 4.1) who underwent successful
H. Pylori eradication between April 1996 and December 1997 were followed up at regular intervals with endoscopic
and histologic examination. The association between macroscopic and histologic regressions of the lesions and the
following patient and lesion characteristics was assessed with univariate analysis: follow-up period, age, sex, serum pepsinogen level, lesion size, lesion location, and histologic gastritis.
RESULTS: The mean follow-up period was 91.9 months (range 44-181 months). Twelve lesions (44.4%) showed macroscopic regression, of which 7 (25.9% of the total) also showed
histologic regression, with the mean duration from H. Pylori eradication to complete macroscopic and histologic
regression being 19.9 months. The other 15 lesions (55.6%) remained stable macroscopically and histologically,
of which 6 (22.2% of the total) progressed to malignancy during the follow-up period. Univariate analysis revealed that female sex (p = .005), smaller lesion size (p = .025), higher baseline
serum pepsinogen II level (p = .041), and absence of intestinal metaplasia in the greater curvature of the corpus
(p = .026) were significantly associated with complete regression.
CONCLUSIONS: Helicobacter pylori eradication may induce regression in some gastric adenomas.
Zaidi SF(1), Refaat A, Zhou Y, Sualeh Muhammad J, Shin MS, Saiki I, Sakurai H,
Helicobacter. 2015 Feb 23. doi: 10.1111/hel.12215. [Epub ahead of print]
BACKGROUND: The interaction of Helicobacter pylori with gastric epithelial cells can result in the activation of
transcription factor NF-κB via TGF-β-activated kinase 1 (TAK1). In this study, we have demonstrated the role of H. pylori in the activation of EGFR via
TAK1-mediated phosphorylation of p38.
MATERIALS AND METHODS: Gastric epithelial AGS or MKN-45 cells were co-cultured with wild-type or cagA(-) H. pylori strains. H. pylori was added to the cells, and the activation of EGFR, p65 (NF-κB) subunit, p38, ERK, and TAK1 was examined by Western blotting. Infected cells were pretreated with or without
ligands, chemical inhibitors, anti-HB-EGF antibody, and siRNAs to evaluate the effects on phosphorylation of various EGFR residues. Fluorescence
microscopy and flow cytometry were performed to detect the internalization of EGFR.
RESULTS: Incubating cells with wild-type and CagA(-) H. pylori strains resulted in the rapid and transient phosphorylation of serine residues of EGFR. RNAi experiments
using siRNA against TAK1 and p38 pathways blocked the phosphorylation of serine residue. Immunofluorescence
and flow cytometry revealed that EGFR was internalized in H. pylori-infected cells after EGFR phosphorylation in a p38-dependent manner. In contrast, pretreatment with gefitinib and anti-HB-EGF antibody did not block both the phosphorylation and internalization of EGFR.
CONCLUSION: Helicobacter pylori induces internalization of EGFR via novel TAK1-p38-serine activation pathway which is independent of HB-EGF. The interaction between TAK1 and EGFR in
H. pylori-infected cells might open new dimensions in understanding H. pylori-associated gastric carcinogenesis.
Park JS , Yeom JS, Seo JH, Lim JY, Park CH, Woo HO, Youn HS, Jun JS, Park JH,Ko GH, Baik SC, Lee WK, Cho MJ,
Helicobacter. 2015 Feb 23. doi: 10.1111/hel.12198. [Epub ahead of print]
OBJECTIVES: The aim of this study was to investigate expression of gastric mucins in children and adolescents and
to assess their relations with age and Helicobacter pylori (H. pylori) infection.
METHODS: Gastric biopsies were collected from 259 pediatric and adulthood patients with gastrointestinal
symptoms among all of patients undergone gastroduodenoscopy from 1990 to 2004 at Gyeongsang National
University hospital and assorted based on H. pylori infection, age, and intestinal metaplasia as follows; H. pylori
infection before 5 years of age or not, H. pylori infection between 5 and 9 years of age or not, H. pylori infection
between 10 and 14 years of age or not, H. pylori infection between 20 and 29 years of age or not and intestinal
metaplasia between 21 and 35 years of age. Total 810 tissue slides from the subjects were examined regarding
expressions of Mucin2 (MUC2), Mucin5AC (MUC5AC), and Mucin6 (MUC6) in nine groups using immunohistochemical
stains. A semiquantitative approach was used to score the staining extent of tissue slide.
RESULTS: Increased expressions of MUC2, MUC5AC, and MUC6 were noted in intestinal metaplasia compared with
subjects infected with H. pylori between 20 and 29 years. Gastric expressions of MUC5AC were decreased in older
than 5 years with H. pylori compared with in older than 5 years without H. pylori (p < .001). Expressions of MUC2
and MUC6 did not change significantly by H. pylori status. Some nuclear expressions of MUC2 and MUC6 were noted
in children without intestinal metaplasia.
CONCLUSIONS: MUC5AC might be affected by chronic H. pylori infection. In addition to biomarkers for intestinal
metaplasia or prognostic factors for gastric cancer in adults, MUC2 and MUC6 in children might have an another role,
based on ectopic gastric nuclear expressions of MUC2 and MUC6 in children without intestinal metaplasia.
melt granulation can enhance the efficacy of Helicobacter pylori eradication.
Aoki H(1), Iwao Y(1), Mizoguchi M(1), Noguchi S(1), Itai S(2).
Eur J Pharm Biopharm. 2015 Feb 19. pii: S0939-6411(15)00094-6. doi:10.1016/j.ejpb.2015.02.012. [Epub ahead of print]
In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine
granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed
sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules
might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated
Helicobacterpylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone.
Gisbert JP(1), Romano M, Gravina AG, Solís-Muñoz P, Bermejo F, Molina-Infante J,
Castro-Fernández M, Ortuño J, Lucendo AJ, Herranz M, Modolell I, Del Castillo F,
Gómez J, Barrio J, Velayos B, Gómez B, Domínguez JL, Miranda A, Martorano M,
Algaba A, Pabón M, Angueira T, Fernández-Salazar L, Federico A, Marín AC,
Aliment Pharmacol Ther. 2015 Feb 23. doi: 10.1111/apt.13128. [Epub ahead of print]
BACKGROUND: The most commonly used second-line Helicobacter pylori eradication regimens are bismuth-containing quadruple therapy and levofloxacin-containing triple therapy, both offering suboptimal results. Combining bismuth and levofloxacin may enhance the
efficacy of rescue eradication regimens.
AIMS: To evaluate the efficacy and tolerability of a second-line quadruple regimen containing levofloxacin and bismuth in patients whose previous H. pylori eradication treatment
METHODS: This was a prospective multicenter study including patients in whom a standard triple therapy (PPI-clarithromycin-amoxicillin) or a non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-metronidazole, either sequential or concomitant) had failed. Esomeprazole (40 mg b.d.), amoxicillin (1 g b.d.),
levofloxacin (500 mg o.d.) and bismuth (240 mg b.d.) was prescribed for 14 days. Eradication was confirmed by
(13) C-urea breath test. Compliance was determined through questioning and recovery of empty medication envelopes.
Incidence of adverse effects was evaluated by questionnaires.
RESULTS: 200 patients were included consecutively (mean age 47 years, 67% women, 13% ulcer). Previous failed
therapy included: standard clarithromycin triple therapy (131 patients), sequential (32) and concomitant (37).
A total of 96% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 91.1% (95%CI = 87-95%) and 90% (95%CI = 86-94%). Cure rates were similar regardless of previous (failed) treatment or country of origin. Adverse effects were
reported in 46% of patients, most commonly nausea (17%) and diarrhoea (16%); 3% were intense but none was
CONCLUSIONS: Fourteen-day bismuth- and levofloxacin-containing quadruple therapy is an effective (≥90% cure rate), simple and safe second-line strategy in patients whose previous standard triple or non-bismuth quadruple (sequential or concomitant) therapies have failed.
a Taiwanese Patient with Mucosa-Associated Lymphoid Tissue Lymphoma.
Kao CY(1), Chen JW(2), Huang YT(1), Sheu SM(3), Sheu BS(3), Wu JJ(4).
Genome Announc. 2015 Feb 19;3(1). pii: e00006-15. doi: 10.1128/genomeA.00006-15.
We present the complete genome sequence of Helicobacter pylori strain Hp238, isolated from a Taiwanese patient
with gastric mucosa-associated lymphoid tissue lymphoma. Importantly, H. pylori strain Hp238 can multiply in THP-1 cells after internalization through the induction of autophagosome formation. These genome data will help to identify
genes associated with H. pylori intracellular multiplication and pathogenesis.
Zhou X(1), Liu W, Gu M, Zhou H, Zhang G.
J Gastroenterol. 2015 Feb 19. [Epub ahead of print]
BACKGROUND: Epidemiological studies have indicated that patients with chronic Helicobacter pylori infection have
an increased risk of developing type 2 diabetes mellitus, but the underlying mechanisms remain largely unknown.
This study aimed to investigate whether H. pylori infection contributes to the development of insulin resistance,
as well as the underlying mechanisms both in vivo and in vitro.
METHODS: The effect of H. pylori infection on glucose metabolism was evaluated in humans and mouse models.
The role of the c-Jun/miR-203/suppressor of cytokine signaling 3 (SOCS3) pathway in H. pylori-induced insulin resistance was determined in vitro and was validated in vivo.
RESULTS: Average fasting glucose levels were increased in patients (P = 0.012) and mice (P = 0.004) with H. pylori
infection. Diabetic mice with H. Pylori infection showed impaired glucose metabolism and insulin tolerance and
hyperinsulinemia. Furthermore, H. pylori infection impaired insulin signaling in primary hepatocytes. H. pylori
infection could upregulate SOCS3, a well-known insulin signaling inhibitor, by downregulating miR-203. SOCS3 overexpression interfered with insulin signaling proteins, and knockdown of SOCS3 alleviated H. pylori-induced impairment of insulin signaling. The transcription factor c-Jun, which affects gene expression, was induced by H. pylori infection and suppressed miR-203 expression.
CONCLUSIONS: Our results demonstrated that H. pylori infection induced hepatic insulin resistance by the c-Jun/miR-203/SOCS3 signaling pathway and provide possible implications with regard to resolving insulin resistance.
Nguyen T(1), Ramsey D, Graham D, Shaib Y, Shiota S, Velez M, Cole R, Anand B,
Vela M, El-Serag HB.
Helicobacter. 2015 Feb 17. doi: 10.1111/hel.12199. [Epub ahead of print]
BACKGROUND: Helicobacter pylori in the United States has been declining in the 1990s albeit less so among blacks
and Hispanics. As the socioeconomic status of racial groups has evolved, it remains unclear whether the prevalence or
the racial and ethnic disparities in the prevalence of H. pylori have changed.
METHODS: This is a cross-sectional study from a Veteran Affairs center among patients aged 40-80 years old who underwent a study esophagogastroduodenoscopy with gastric biopsies, which were cultured for
H. pylori irrespective of findings on histopathology. Positive H. pylori was defined as positive culture or
histopathology (stained organism combined with active gastritis). We calculated age-, race-, and birth cohort-specific H. pylori prevalence rates and examined predictors of H. pylori infection in logistic regression models.
RESULTS: We analyzed data on 1200 patients; most (92.8%) were men and non-Hispanic white (59.9%) or black (28.9%). H. pylori was positive in 347 (28.9%) and was highest among black males
aged 50-59 (53.3%; 44.0-62.4%), followed by Hispanic males aged 60-69 (48.1%; 34.2-62.2%), and lowest in non-Hispanic white males aged 40-49 (8.2%; 2.7-20.5%). In multivariate analysis, age group 50-59 was significantly associated with H. pylori (adjusted odds ratio (OR), 2.32; 95% confidence interval (CI), 1.21-4.45) compared with those aged 40-49, and with black race (adjusted OR, 2.57; 95% CI, 1.83-3.60) and Hispanic ethnicity (adjusted OR, 3.01; 95% CI, 1.70-5.34) compared with non-Hispanic white. Irrespective of age group, patients born during 1960-1969 had a lower risk of H. pylori (adjusted OR, 0.45; 95% CI, 0.22-0.96) compared to those born in 1930-1939. Those with some college education were less likely to have H. Pylori compared to those with no college
education (adjusted OR 0.51; 95% CI, 0.37-0.69).
CONCLUSION: Among veterans, the prevalence of active H. pylori remains high (28.9%) with even higher rates in
blacks and Hispanics with lower education levels.
Zhu Y(1), Chen M(2), Gong Y(2), Liu Z(3), Li A(2), Kang D(2), Han F(2), Liu J(2),
Liu J(4), Yuan Y(2).
FEMS Microbiol Lett. 2015 Feb 16. pii: fnv023. [Epub ahead of print]
ThoSugh Helicobacter pylori (H. pylori) has been classified as class I carcinogen, key virulence factorabs(s) generated by H. pylori that causes gastric cancer remains to be fully determined. Here, we show that deletion of
peptidyl-prolyl cis-trans isomerase (PPIase) prevented H. pylori from stimulating human gastric epithelial cell (AGS) proliferation.
Consistent with this observation, ectopic expression of H. pylori PPIase promoted AGS cell proliferation and
anchorage-independent growth. To gain insight into the biochemical mechanism of PPIase-induced effect, early signal events involved in mitogenic signaling pathways were evaluated. Expression of H. pylori
PPIase caused an increase in basal as well as EGF-stimulated phosphorylation of ERK and EGF receptor at Tyr1086. Treatment with MEK inhibitor completely blocked
PPIase-induced cell proliferation. Our results suggest that H. pylori PPIase has the potential to activate mitogenic signaling
pathway and to promote transformation of gastric epithelial cells. H. pylori PPIase may represent a novel target for
therapeutic management of gastric cancer patients.
本研究探讨了TLR1 rs4833095, TLR10 rs10004195和TLR10 rs4129009基因多态性与幽门螺杆菌易感性和胃黏膜病变之间的相关性，关联分析结果表明TLR1 rs4833095 T等位基因或CT 基因型与幽门螺杆菌低感染率、慢性萎缩性胃炎和肠上皮化生低风险相关。TLR10 rs10004195 T 等位基因亦和慢性萎缩性胃炎低风险相关。单倍型分析显示rs4833095和rs10004195TT基因型在幽门螺杆菌易感性和胃部癌前病变中起保护性作用。
risk of gastric lesions in a high-risk Chinese population.
Tang FB(1), Li ZX(1), Wang YM(1), Zhang L(1), Ma JL(1), Zhou T(1), Zhang Y(1),
Gao JJ(1), Wu S(1), Yang T(1), You WC(2), Pan KF(3).
Infect Genet Evol. 2015 Feb 14;31C:263-269. doi: 10.1016/j.meegid.2015.02.005.
[Epub ahead of print]
Genetic polymorphisms of Toll-like receptor (TLR) 1 and 10 may influence Helicobacter pylori (H. pylori) susceptibility. To evaluate associations
between TLR1 and 10 polymorphisms, H. pylori infection, and precancerous gastric lesions, a population-based study was conducted in a high-risk Chinese population. Three single-nucleotide polymorphisms, TLR1 rs4833095, TLR10 rs10004195, and TLR10 rs4129009 were genotyped by TaqMan
SNP genotyping assay in 2553 participants with diverse gastric lesions. The status of H. pylori infection was
determined by (13)C-urea breath test. TLR1 rs4833095 T and TLR10 rs10004195 T alleles were the minor alleles and showed in linkage
disequilibrium (D'=0.98, r(2)=0.73) in the Chinese population. A decreased risk of H. pylori infection was observed in subjects with TLR1
rs4833095 CT genotype [adjusted odds ratio (OR)=0.80; 95% confidence interval (CI): 0.66-0.96] or T allele (OR=0.82; 95%CI: 0.69-0.99). Moreover, subjects carrying TLR1 rs4833095 TT genotype were associated with reduced risks of chronic
atrophic gastritis (CAG, OR=0.66; 95%CI: 0.45-0.97) and intestinal metaplasia (IM, OR=0.57; 95%CI: 0.36-0.90). The risk of CAG was also decreased in subjects carrying TLR10 rs10004195 T allele (OR=0.75; 95%CI:0.57-0.99). Furthermore, haplotype analysis indicated that haplotype TT of rs4833095 and rs10004195 had a protective
effect on H. pylori infection (OR=0.83; 95%CI: 0.72-0.96) or precancerous gastric lesions (OR=0.78; 95%CI: 0.64-0.96 for CAG, and OR=0.74; 95%CI: 0.57-0.96 for IM). These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori
susceptibility and gastric pathogenesis.
Shiota S(1), Reddy R(2), Alsarraj A(3), El-Serag HB(4), Graham DY(1).
Clin Gastroenterol Hepatol. 2015 Feb 11. pii: S1542-3565(15)00122-6. doi: 10.1016/j.cgh.2015.02.005. [Epub ahead of print]
BACKGROUND & AIMS: The most recent information published on resistance of Helicobacter pylori to antibiotics
in a large population in the United States is more than 10 y old. We assessed the susceptibility of H pylori to
antibiotics among patients in a large metropolitan hospital, as well as demographic, clinical, and life-style factors associated with antimicrobial resistance.
METHODS: We performed a cross-sectional study at the Houston Veterans Affairs Medical Center of a random sample of 656 patients (90.2% men) from
a cohort of 1559 undergoing esophagastroduodenoscopy with collection of gastric biopsies from 2009 through 2013.
We performed culture analyses of gastric tissues to detect H.pylori. The minimum inhibitory concentrations of
amoxicillin, clarithromycin, metronidazole, levofloxacin, and tetracycline were determined by the Epsilometer test.
Logistic regression analysis was performed to estimate the association between risk factors and antimicrobial
RESULTS: Biopsies from 135 subjects (20.6%) tested positive for H pylori; 128 of these were from men (94.8%).
Only 65 strains were susceptible to all 5 antibiotics. The prevalence of resistance to levofloxacin was 31.3%
(95% confidence interval [CI], 23.1-39.4), to metronidazole was 20.3% (95% CI, 13.2-27.4), to clarithromycin was 16.4% (95% CI, 9.9-22.9), and to tetracycline was 0.8% (95% CI, 0.0-2.3). No isolate was resistant to amoxicillin. Clarithromycin resistance increased from 9.1% in 2009-2010 to&nbs