Probiotic Lactobacillus spp. act Against Helicobacter pylori-induced Inflammation

The bacterial species, Helicobacter pylori, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics. Lactobacillus spp., on the other hand, possess probiotic activities that have beneficial effects in humans. However, the mechanisms by which Lactobacillus spp. harbor favorable functions and act against H. pylori infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains, Lactobacillus rhamnosus and Lactobacillus acidophilus, termed GMNL-74 and GMNL-185, respectively, to inhibit H. pylori growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-H. pylori. In addition, an in vitro cell-based model revealed that the inhibition of H. pylori adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the Lactobacillus strains. In vivo studies demonstrated that colonization of H. pylori and induced inflammation in the mouse stomach were also alleviated by these Lactobacillus strains. Furthermore, the abundance of beneficial gut bacteria, including Bifidobacterium spp. and Akkermansia muciniphilia, were significantly increased in H. pylori-infected mice treated with GMNL-74 and GMNL-185. These results demonstrate that Lactobacillus spp. ameliorate H. pylori-induced inflammation and supports beneficial gut specific bacteria that act against H. pylori infection.

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Systematic Analysis of Monoterpenes: Advances and Challenges in the Treatment of Peptic Ulcer Diseases

Biomolecules ◽

10.3390/biom10020265 ◽

2020 ◽

Vol 10 (2) ◽

pp. 265 ◽

Cited By ~ 1

Author(s):

Larissa Lucena Périco ◽

Maycon Tavares Emílio-Silva ◽

Rie Ohara ◽

Vinícius Peixoto Rodrigues ◽

Gabriela Bueno ◽

...

Keyword(s):

Helicobacter Pylori ◽

Peptic Ulcer ◽

Complex Disease ◽

Pharmacological Action ◽

In Vivo Studies ◽

Systematic Analysis ◽

Ulcer Disease ◽

H Pylori

Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the understanding of PUD has changed a lot with the discovery of Helicobacter pylori infection. However, this disease continues to be a challenge due to side-effects, incidence of relapse from use of various anti-ulcer medicines, and the rapid appearance of antimicrobial resistance with current H. pylori therapies. Consequently, there is the need to identify more effective and safe anti-ulcer agents. The search for new therapies with natural products is a viable alternative and has been encouraged. The literature reports the importance of monoterpenes based on the extensive pharmacological action of this class, including wound healing and anti-ulcerogenic agents. In the present study, 20 monoterpenes with anti-ulcerogenic properties were evaluated by assessing recent in vitro and in vivo studies. Here, we review the anti-ulcer effects of monoterpenes against ulcerogenic factors such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori, highlighting challenges in the field.

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Limited Role of Lipopolysaccharide Lewis Antigens in Adherence of Helicobacter pylori to the Human Gastric Epithelium

Infection and Immunity ◽

10.1128/iai.71.5.2876-2880.2003 ◽

2003 ◽

Vol 71 (5) ◽

pp. 2876-2880 ◽

Cited By ~ 27

Author(s):

Jafar Mahdavi ◽

Thomas Borén ◽

Christina Vandenbroucke-Grauls ◽

Ben J. Appelmelk

Keyword(s):

Helicobacter Pylori ◽

Gastric Epithelium ◽

In Vivo Studies ◽

Minor Role ◽

Human Gastric Mucosa ◽

H Pylori

ABSTRACT In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Lex) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Lex-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Lex-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion.

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Phytochemicals in Helicobacter pylori Infections: What Are We Doing Now?

International Journal of Molecular Sciences ◽

10.3390/ijms19082361 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2361 ◽

Cited By ~ 35

Author(s):

Bahare Salehi ◽

Farukh Sharopov ◽

Miquel Martorell ◽

Jovana Rajkovic ◽

Adedayo Ademiluyi ◽

...

Keyword(s):

Helicobacter Pylori ◽

Plant Extracts ◽

Bioactive Molecules ◽

Herbal Remedies ◽

In Vivo Studies ◽

Modes Of Action ◽

Urease Inhibitory ◽

H Pylori

In this critical review, plant sources used as effective antibacterial agents against Helicobacter pylori infections are carefully described. The main intrinsic bioactive molecules, responsible for the observed effects are also underlined and their corresponding modes of action specifically highlighted. In addition to traditional uses as herbal remedies, in vitro and in vivo studies focusing on plant extracts and isolated bioactive compounds with anti-H. pylori activity are also critically discussed. Lastly, special attention was also given to plant extracts with urease inhibitory effects, with emphasis on involved modes of action.

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Unraveling the Novel Effect of Patchouli Alcohol Against the Antibiotic Resistance of Helicobacter pylori

Frontiers in Microbiology ◽

10.3389/fmicb.2021.674560 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuanzun Zhong ◽

Liyao Tang ◽

Qiuhua Deng ◽

Li Jing ◽

Jiao Zhang ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibiotic Resistance ◽

Efflux Pump ◽

Underlying Mechanism ◽

Gastrointestinal Diseases ◽

Bactericidal Effect ◽

Patchouli Alcohol ◽

H Pylori

The long-term colonization of Helicobacter pylori can cause various gastrointestinal diseases, and its high genetic variability is prone to antibiotic resistance and leads to failure of clinical treatment. Intracellular survival also contributes to the drug tolerance of H. pylori. Patchouli alcohol (PA) shows a highly efficient activity against H. pylori in vitro and in vivo. And this study aims to explore whether PA can reduce the resistance of H. pylori and determine the underlying mechanism. Checkerboard and time–kill bactericidal curve assay reveal that the combination of PA and clarithromycin (CLR) promoted the inhibition and bactericidal effect against H. pylori. Stimulation of CLR leads to the internalization of H. pylori, but PA can effectively inhibit the invasion induced by CLR. Compared with antibiotics, PA remarkably eradicated the intracellular H. pylori, and this intracellular sterilized ability was further improved in combination with antibiotics (CLR and metronidazole). The expression of H. pylori efflux pump genes (hp0605, hp1327, and hp1489) was dose-dependently downregulated by PA. Digital droplet PCR indicated that the H. pylori mutant of A2143G can be inhibited by PA. Cellular uptake and transport assays showed that PA is rapidly absorbed, which promotes its activity against intracellular bacteria. Therefore, PA can act synergistically with CLR as a candidate treatment against drug-resistant H. pylori.

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Synthesis, Molecular Modelling and Antibacterial Activity Against Helicobacter pylori of Novel Diflunisal Derivatives as Urease Enzyme Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180627130208 ◽

2019 ◽

Vol 16 (4) ◽

pp. 392-400 ◽

Cited By ~ 2

Author(s):

Göknil Pelin Coşkun ◽

Teodora Djikic ◽

Sadık Kalaycı ◽

Kemal Yelekçi ◽

Fikrettin Şahin ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antibacterial Activity ◽

Enzyme Inhibitors ◽

Binding Modes ◽

Bacterial Strains ◽

Urease Enzyme ◽

H Pylori ◽

Ulcer Treatment ◽

Main Factor

Background:The main factor for the prolongation of the ulcer treatment in the gastrointestinal system would be Helicobacter pylori infection, which can possibly lead to gastrointestinal cancer. Triple therapy is the treatment of choice by today's standards. However, observed resistance among the bacterial strains can make the situation even worse. Therefore, there is a need to discover new targeted antibacterial therapy in order to make success in the eradication of H. pylori infections.Methods:The targeted therapy rule is to identify the related macromolecules that are responsible for the survival of the bacteria. Thus, 2-[(2',4'-difluoro-4-hydroxybiphenyl-3-yl)carbonyl]-N- (substituted)hydrazinocarbothioamide (3-13) and 5-(2',4'-difluoro-4-hydroxybiphenyl-3-yl)-4- (substituted)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (14-17) were synthesized and evaluated for antibacterial activity in vitro against H. pylori.Results:All of the tested compounds showed remarkable antibacterial activity compared to the standard drugs (Ornidazole, Metronidazole, Nitrimidazin and Clarithromycin). Compounds 4 and 13 showed activity as 2µg/ml MIC value.Conclusion:In addition, we have investigated binding modes and energy of the compounds 4 and 13 on urease enzyme active by using the molecular docking tools.

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Enhanced fitness of a Helicobacter pylori babA mutant in a murine model

Infection and Immunity ◽

10.1128/iai.00725-20 ◽

2021 ◽

Author(s):

M. Lorena Harvey ◽

Aung Soe Lin ◽

Lili Sun ◽

Tatsuki Koyama ◽

Jennifer H. B. Shuman ◽

...

Keyword(s):

Helicobacter Pylori ◽

Outer Membrane Proteins ◽

Population Diversity ◽

Fitness Advantage ◽

Neutral Locus ◽

Mutant Strains ◽

Bacterial Fitness ◽

H Pylori

Helicobacter pylori genomes encode >60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify hop mutant strains that exhibit altered fitness in vivo compared to fitness in vitro , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of hop mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time in vivo compared to changes detected in the populations during library passage in vitro . The control library proliferated as a relatively stable community in vitro, but there was a reduction in the population diversity of this library in vivo and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a non-selective bottleneck in vivo . We did not identify any OMP mutants exhibiting fitness defects exclusively in vivo without corresponding fitness defects in vitro . Conversely, a babA mutant exhibited a strong fitness advantage in vivo but not in vitro . These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.

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Lactobacillus johnsonii La1 Attenuates Helicobacter pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.12.1378-1386.2005 ◽

2005 ◽

Vol 12 (12) ◽

pp. 1378-1386 ◽

Cited By ~ 56

Author(s):

Dionyssios N. Sgouras ◽

Effrosini G. Panayotopoulou ◽

Beatriz Martinez-Gonzalez ◽

Kalliopi Petraki ◽

Spyros Michopoulos ◽

...

Keyword(s):

Helicobacter Pylori ◽

Lamina Propria ◽

Serum Levels ◽

Favorable Effect ◽

Lactobacillus Johnsonii ◽

Ags Cells ◽

Inflammatory Infiltration ◽

H Pylori

ABSTRACT In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P = 0.038) and neutrophilic (P = 0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P = 0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P = 0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.

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Therapeutic effects of Zuojin Pill on Helicobacter pylori-induced chronic atrophic gastritis through JMJD2B/COX-2/VEGF signaling axis

10.21203/rs.3.rs-20652/v2 ◽

2020 ◽

Author(s):

Shihua Wu ◽

Chunmei Bao ◽

Ruilin Wang ◽

Xiaomei Zhang ◽

Sijia Gao ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cell Viability ◽

Atrophic Gastritis ◽

Chronic Atrophic Gastritis ◽

Gastric Mucosal Damage ◽

Therapeutic Effects ◽

Cox 2 ◽

H Pylori

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

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A Novel 3-Deoxy-d-manno-Octulosonic Acid (Kdo) Hydrolase That Removes the Outer Kdo Sugar of Helicobacter pylori Lipopolysaccharide

Journal of Bacteriology ◽

10.1128/jb.187.10.3374-3383.2005 ◽

2005 ◽

Vol 187 (10) ◽

pp. 3374-3383 ◽

Cited By ~ 34

Author(s):

Christopher Stead ◽

An Tran ◽

Donald Ferguson ◽

Sara McGrath ◽

Robert Cotter ◽

...

Keyword(s):

Helicobacter Pylori ◽

Lipid A ◽

In Vitro Assay ◽

Spectrometric Analysis ◽

Vitro Assay ◽

The Core ◽

H Pylori

ABSTRACT The lipid A domain anchors lipopolysaccharide (LPS) to the outer membrane and is typically a disaccharide of glucosamine that is both acylated and phosphorylated. The core and O-antigen carbohydrate domains are linked to the lipid A moiety through the eight-carbon sugar 3-deoxy-d-manno-octulosonic acid known as Kdo. Helicobacter pylori LPS has been characterized as having a single Kdo residue attached to lipid A, predicting in vivo a monofunctional Kdo transferase (WaaA). However, using an in vitro assay system we demonstrate that H. pylori WaaA is a bifunctional enzyme transferring two Kdo sugars to the tetra-acylated lipid A precursor lipid IVA. In the present work we report the discovery of a Kdo hydrolase in membranes of H. pylori capable of removing the outer Kdo sugar from Kdo2-lipid A. Enzymatic removal of the Kdo group was dependent upon prior removal of the 1-phosphate group from the lipid A domain, and mass spectrometric analysis of the reaction product confirmed the enzymatic removal of a single Kdo residue by the Kdo-trimming enzyme. This is the first characterization of a Kdo hydrolase involved in the modification of gram-negative bacterial LPS.

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3-Pentylcatechol, a Non-Allergenic Urushiol Derivative, Displays Anti-Helicobacter pylori Activity In Vivo

Pharmaceuticals ◽

10.3390/ph13110384 ◽

2020 ◽

Vol 13 (11) ◽

pp. 384

Author(s):

Hang Yeon Jeong ◽

Tae Ho Lee ◽

Ju Gyeong Kim ◽

Sueun Lee ◽

Changjong Moon ◽

...

Keyword(s):

Helicobacter Pylori ◽

Triple Therapy ◽

Inflammatory Cells ◽

Control Group ◽

Vitro Assay ◽

Low Concentrations ◽

H Pylori ◽

Stomach Mucous Membrane

We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.

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