scholarly journals Effects of Proton Pump Inhibitors on the Gastric Mucosa-Associated Microbiota in Dyspeptic Patients

2016 ◽  
Vol 82 (22) ◽  
pp. 6633-6644 ◽  
Author(s):  
Francesco Paroni Sterbini ◽  
Alessandra Palladini ◽  
Luca Masucci ◽  
Carlo Vittorio Cannistraci ◽  
Roberta Pastorino ◽  
...  

ABSTRACTBesides being part of anti-Helicobacter pyloritreatment regimens, proton pump inhibitors (PPIs) are increasingly being used to treat dyspepsia. However, little is known about the effects of PPIs on the human gastric microbiota, especially those related toH. pyloriinfection. The goal of this study was to characterize the stomach microbial communities in patients with dyspepsia and to investigate their relationships with PPI use andH. pyloristatus. Using 16S rRNA gene pyrosequencing, we analyzed the mucosa-associated microbial populations of 24 patients, of whom 12 were treated with the PPI omeprazole and 9 (5 treated and 4 untreated) were positive forH. pyloriinfection. TheProteobacteria,Firmicutes,Bacteroidetes,Fusobacteria, andActinobacteriaphyla accounted for 98% of all of the sequences, withHelicobacter,Streptococcus, andPrevotellaranking among the 10 most abundant genera.H. pyloriinfection or PPI treatment did not significantly influence gastric microbial species composition in dyspeptic patients. Principal-coordinate analysis of weighted UniFrac distances in these communities revealed clear but significant separation according toH. pyloristatus only. However, in PPI-treated patients,Firmicutes, particularlyStreptococcaceae, were significantly increased in relative abundance compared to those in untreated patients. Consistently,Streptococcuswas also found to significantly increase in relation to PPI treatment, and this increase seemed to occur independently ofH. pyloriinfection. Our results suggest thatStreptococcusmay be a key indicator of PPI-induced gastric microbial composition changes in dyspeptic patients. Whether the gastric microbiota alteration contributes to dyspepsia needs further investigation.IMPORTANCEAlthough PPIs have become a popular treatment choice, a growing number of dyspeptic patients may be treated unnecessarily. We found that patients treated with omeprazole showed gastric microbial communities that were different from those of untreated patients. These differences regarded the abundances of specific taxa. By understanding the relationships between PPIs and members of the gastric microbiota, it will be possible to envisage new strategies for better managing patients with dyspepsia.

2021 ◽  
Vol 59 (5) ◽  
Author(s):  
Anthony Mannion ◽  
JoAnn Dzink-Fox ◽  
Zeli Shen ◽  
M. Blanca Piazuelo ◽  
Keith T. Wilson ◽  
...  

ABSTRACT Colombia, South America has one of the world’s highest burdens of Helicobacter pylori infection and gastric cancer. While multidrug antibiotic regimens can effectively eradicate H. pylori, treatment efficacy is being jeopardized by the emergence of antibiotic-resistant H. pylori strains. Moreover, the spectrum of and genetic mechanisms for antibiotic resistance in Colombia is underreported. In this study, 28 H. pylori strains isolated from gastric biopsy specimens from a high-gastric-cancer-risk (HGCR) population living in the Andes Mountains in Túquerres, Colombia and 31 strains from a low-gastric-cancer-risk (LGCR) population residing on the Pacific coast in Tumaco, Colombia were subjected to antibiotic susceptibility testing for amoxicillin, clarithromycin, levofloxacin, metronidazole, rifampin, and tetracycline. Resistance-associated genes were amplified by PCR for all isolates, and 29 isolates were whole-genome sequenced (WGS). No strains were resistant to amoxicillin, clarithromycin, or rifampin. One strain was resistant to tetracycline and had an A926G mutation in its 16S rRNA gene. Levofloxacin resistance was observed in 12/59 isolates and was significantly associated with N87I/K and/or D91G/Y mutations in gyrA. Most isolates were resistant to metronidazole; this resistance was significantly higher in the LGCR (31/31) group compared to the HGCR (24/28) group. Truncations in rdxA and frxA were present in nearly all metronidazole-resistant strains. There was no association between phylogenetic relationship and resistance profiles based on WGS analysis. Our results indicate H. pylori isolates from Colombians exhibit multidrug antibiotic resistance. Continued surveillance of H. pylori antibiotic resistance in Colombia is warranted in order to establish appropriate eradication treatment regimens for this population.


2021 ◽  
Vol 35 ◽  
pp. 205873842110303
Author(s):  
Wenwen Gao ◽  
Xiang Zhang ◽  
Yanhui Yin ◽  
Shuwen Yu ◽  
Lu Wang

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.


AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shenzheng Zeng ◽  
Sukontorn Khoruamkid ◽  
Warinphorn Kongpakdee ◽  
Dongdong Wei ◽  
Lingfei Yu ◽  
...  

Abstract The Pacific white shrimp, with the largest production in shrimp industry, has suffered from multiple severe viral and bacterial diseases, which calls for a more reliable and environmentally friendly system to promote shrimp culture. The “Aquamimicry system”, mimicking the nature of aquatic ecosystems for the well-being of aquatic animals, has effectively increased shrimp production and been adapted in many countries. However, the microbial communities in the shrimp intestine and surrounding environment that act as an essential component in Aquamimicry remain largely unknown. In this study, the microbial composition and diversity alteration in shrimp intestine, surrounding water and sediment at different culture stages were investigated by high throughput sequencing of 16S rRNA gene, obtaining 13,562 operational taxonomic units (OTUs). Results showed that the microbial communities in shrimp intestine and surrounding environment were significantly distinct from each other, and 23 distinguished taxa for each habitat were further characterized. The microbial communities differed significantly at different culture stages, confirmed by a great number of OTUs dramatically altered during the culture period. A small part of these altered OTUs were shared between shrimp intestine and surrounding environment, suggesting that the microbial alteration of intestine was not consistent with that of water and sediment. Regarding the high production of Aquamimicry farm used as a case in this study, the dissimilarity between intestinal and surrounding microbiota might be considered as a potential indicator for healthy status of shrimp farming, which provided hints on the appropriate culture practices to improve shrimp production.


2013 ◽  
Vol 80 (1) ◽  
pp. 177-183 ◽  
Author(s):  
Lavane Kim ◽  
Eulyn Pagaling ◽  
Yi Y. Zuo ◽  
Tao Yan

ABSTRACTThe impact of substratum surface property change on biofilm community structure was investigated using laboratory biological aerated filter (BAF) reactors and molecular microbial community analysis. Two substratum surfaces that differed in surface properties were created via surface coating and used to develop biofilms in test (modified surface) and control (original surface) BAF reactors. Microbial community analysis by 16S rRNA gene-based PCR-denaturing gradient gel electrophoresis (DGGE) showed that the surface property change consistently resulted in distinct profiles of microbial populations during replicate reactor start-ups. Pyrosequencing of the bar-coded 16S rRNA gene amplicons surveyed more than 90% of the microbial diversity in the microbial communities and identified 72 unique bacterial species within 19 bacterial orders. Among the 19 orders of bacteria detected,BurkholderialesandRhodocyclalesof theBetaproteobacteriaclass were numerically dominant and accounted for 90.5 to 97.4% of the sequence reads, and their relative abundances in the test and control BAF reactors were different in consistent patterns during the two reactor start-ups. Three of the five dominant bacterial species also showed consistent relative abundance changes between the test and control BAF reactors. The different biofilm microbial communities led to different treatment efficiencies, with consistently higher total organic carbon (TOC) removal in the test reactor than in the control reactor. Further understanding of how surface properties affect biofilm microbial communities and functional performance would enable the rational design of new generations of substrata for the improvement of biofilm-based biological treatment processes.


Author(s):  
V.V. Parkhomenko ◽  
І.М. Skrypnyk ◽  
І.І. Starchenko ◽  
O.F. Gopko

The non-steroidal anti-inflammatory drugs (NSAIDs) in general clinical practice can provoke the development of NSAID-induced gastropathy, which can be complicated by bleeding. The aim of this article was to evaluate the effect of eupatilin on histological changes of the gastric mucosa in patients with NSAID-induced gastropathy and concomitant ischemic heart disease depending on the association with Helicobacter pylori. The study included 125 patients with NSAID-gastropathy and concomitant stable ischemic heart disease I-II functional class. Patients were divided into two groups: I (n=82) included individuals with NSAID-gastropathy, which was not associated with H. pylori, while II (n=43) included individuals with H. pylori-induced gastropathy. Depending on the prescribed treatment complexes, patients were subdivided as follows: I-A (n=44) included patients, who took proton pump inhibitors in standard doses and II-A group (n=23) included patients, who received antihelicobacter therapy according to Maastricht V (2016) guidelines. Patients of groups I-B (n=38) and II-B (n=20) were additionally prescribed 60 mg of eupatilin (1 tablet) 3 times a day for 28 days. The upper endoscopy with the gastric mucosa biopsy, followed by histological examination was done at the beginning of treatment and in 45±2 days. The severity of gastric mucosa erosive and ulcerative injury was assessed endoscopically using a modified Lanzascore scale; morphological changes were evaluated by a semi-quantitative method on a visual-analogue scale. H. pylori is an independent and significant factor determining the severity of endoscopic and morphological changes in NSAID-gastropathy patients with concomitant ischemic heart disease. Acid-suppressive and antihelicobacter therapy can reduce the intensity of the structural injury of the gastric mucosa, but the identified changes substantiate the feasibility of long-term proton pump inhibitors prescribed to the patients with NSAID-gastropathy. Prescribing eupatilin against the background of basic therapy can significantly reduce the severity of erosive-ulcerative gastric mucosa injury assessed by Lanzascore scale while histomorphological parameters by reducing the activity of neutrophilic inflammation, protective effect on mucosal barrier resistance and microcirculatory condition.


2014 ◽  
Vol 80 (16) ◽  
pp. 4854-4864 ◽  
Author(s):  
Myrna E. Jacobson Meyers ◽  
Jason B. Sylvan ◽  
Katrina J. Edwards

ABSTRACTSeafloor basalts are widely distributed and host diverse prokaryotic communities, but no data exist concerning the metabolic rates of the resident microbial communities. We present here potential extracellular enzyme activities of leucine aminopeptidase (LAP) and alkaline phosphatase (AP) measured on basalt samples from different locations on Loihi Seamount, HI, coupled with analysis of prokaryotic biomass and pyrosequencing of the bacterial 16S rRNA gene. The community maximum potential enzyme activity (Vmax) of LAP ranged from 0.47 to 0.90 nmol (g rock)−1h−1; theVmaxfor AP was 28 to 60 nmol (g rock)−1h−1. TheKmof LAP ranged from 26 to 33 μM, while theKmfor AP was 2 to 7 μM. Bacterial communities on Loihi basalts were comprised primarily ofAlpha-,Delta-, andGammaproteobacteria,Bacteroidetes, andPlanctomycetes. The putative ability to produce LAP is evenly distributed across the most commonly detected bacterial orders, but the ability to produce AP is likely dominated by bacteria in the ordersXanthomonadales,Flavobacteriales, andPlanctomycetales. The enzyme activities on Loihi basalts were compared to those of other marine environments that have been studied and were found to be similar in magnitude to those from continental shelf sediments and orders of magnitude higher than any measured in the water column, demonstrating that the potential for exposed basalts to transform organic matter is substantial. We propose that microbial communities on basaltic rock play a significant, quantifiable role in benthic biogeochemical processes.


mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Anna M. Seekatz ◽  
Matthew K. Schnizlein ◽  
Mark J. Koenigsknecht ◽  
Jason R. Baker ◽  
William L. Hasler ◽  
...  

ABSTRACTAlthough the microbiota in the proximal gastrointestinal (GI) tract have been implicated in health and disease, much about these microbes remains understudied compared to those in the distal GI tract. This study characterized the microbiota across multiple proximal GI sites over time in healthy individuals. As part of a study of the pharmacokinetics of oral mesalamine administration, healthy, fasted volunteers (n = 8; 10 observation periods total) were orally intubated with a four-lumen catheter with multiple aspiration ports. Samples were taken from stomach, duodenal, and multiple jejunal sites, sampling hourly (≤7 h) to measure mesalamine (administered att = 0), pH, and 16S rRNA gene-based composition. We observed a predominance ofFirmicutesacross proximal GI sites, with significant variation compared to stool. The microbiota was more similar within individuals over time than between subjects, with the fecal microbiota being unique from that of the small intestine. The stomach and duodenal microbiota displayed highest intraindividual variability compared to jejunal sites, which were more stable across time. We observed significant correlations in the duodenal microbial composition with changes in pH; linear mixed models identified positive correlations with multipleStreptococcusoperational taxonomic units (OTUs) and negative correlations with multiplePrevotellaandPasteurellaceaeOTUs. Few OTUs correlated with mesalamine concentration. The stomach and duodenal microbiota exhibited greater compositional dynamics than the jejunum. Short-term fluctuations in the duodenal microbiota were correlated with pH. Given the unique characteristics and dynamics of the proximal GI tract microbiota, it is important to consider these local environments in health and disease states.IMPORTANCEThe gut microbiota are linked to a variety of gastrointestinal diseases, including inflammatory bowel disease. Despite this importance, microbiota dynamics in the upper gastrointestinal tract are understudied. Our article seeks to understand what factors impact microbiota dynamics in the healthy human upper gut. We found that the upper gastrointestinal tract contains consistently prevalent bacterial OTUs that dominate the overall community. Microbiota variability is highest in the stomach and duodenum and correlates with pH.


2019 ◽  
Vol 12 ◽  
pp. 175628481983451 ◽  
Author(s):  
Ka Shing Cheung ◽  
Wai K. Leung

Gastric cancer remains one of the leading cancers in the world with a high mortality, particularly in East Asia. Helicobacter pylori infection accounts for the majority of the noncardia gastric cancers by triggering gastric inflammation and subsequent neoplastic progression. Eradication of H. pylori can reduce, but not totally eliminate, subsequent risk of developing gastric cancer. Proton-pump inhibitors (PPIs) are one of the most widely prescribed medications worldwide. With their profound gastric-acid suppression, there are concerns about a possible carcinogenic role in gastric cancer, due to induced hypergastrinemia, gastric atrophy and bacterial overgrowth in the stomach. While randomized clinical trials to establish causality between long-term PPI use and gastric cancer are lacking, current evidence based on observational studies suggests PPIs are associated with an increased gastric cancer risk. However, opinions on causality remain divergent due to unmeasured and possible residual confounding in various studies. Our recent study has showed that even after H. pylori eradication, long-term PPI use is still associated with an increased risk of gastric cancer by more than twofold. Hence, long-term PPIs should be used judiciously after considering individual’s risk–benefit profile, particularly among those with history of H. pylori infection. Further well-designed prospective studies are warranted to confirm the potential role of PPIs in gastric cancer according to baseline gastric histology and its interaction with other chemopreventive agents like aspirin, statins and metformin.


1996 ◽  
Vol 40 (3) ◽  
pp. 621-626 ◽  
Author(s):  
J E Sjöström ◽  
J Fryklund ◽  
T Kühler ◽  
H Larsson

Factors affecting the in vitro antibacterial activity of omeprazole were studied. Our data show that 3H-labeled omeprazole covalently bound to Helicobacter pylori and to other gram-negative and gram-positive bacteria. The compound was found to bind to a broad range of proteins in H. pylori, and at pH 5, binding was enhanced 15-fold compared with binding at pH 7. The bactericidal activity correlated to the degree of binding, and at pH 5, a pH at which omeprazole readily converts to the active sulfenamide form, beta-mercaptoethanol, a known scavenger of sulfenamide, and fetal calf serum, to which noncovalent protein binding of omeprazole is known to occur, reduced the level of binding and almost entirely abolished the bactericidal activity. At pH 7 the killing activities of omeprazole and structural analogs (e.g., proton pump inhibitors) were dependent on the time-dependent conversion (half-life) to the corresponding sulfenamide. The bactericidal activity exerted by the sulfenamide form at pH 5 was not specific for the genus Helicobacter. However, in brucella broth at pH 7 with 10% fetal calf serum, only Helicobacter spp. were susceptible to omeprazole, with MBCs in the range of 32 to 64 micrograms/ml, and MBCs for more stable proton pump inhibitors were higher. Wild-type H. pylori and its isogenic urease-deficient mutant were equally susceptible to omeprazole. Thus, the urease is not a lethal target for omeprazole action in H. pylori. In conclusion, the antibacterial activities of omeprazole and analogs are dependent on pH and the composition of the medium used. Thus, at a low pH in buffer, these compounds have a nonselective action, whereas in broth at neutral pH, the mechanism of action is selective for Helicobacter spp.


mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Jennifer M. Noto ◽  
Joseph P. Zackular ◽  
Matthew G. Varga ◽  
Alberto Delgado ◽  
Judith Romero-Gallo ◽  
...  

ABSTRACT Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer. To investigate the combinatorial effects of these determinants in an in vivo model of gastric cancer, Mongolian gerbils were infected with the carcinogenic cag+ H. pylori strain 7.13 or a 7.13 cagA isogenic mutant, and microbial DNA extracted from gastric tissue was analyzed by 16S rRNA sequencing. Infection with H. pylori significantly increased gastric inflammation and injury, decreased α-diversity, and altered microbial community structure in a cagA-dependent manner. The effect of iron deficiency on gastric microbial communities was also investigated within the context of infection. H. pylori-induced injury was augmented under conditions of iron deficiency, but despite differences in gastric pathology, there were no significant differences in α- or β-diversity, phyla, or operational taxonomic unit (OTU) abundance among infected gerbils maintained on iron-replete or iron-depleted diets. However, when microbial composition was stratified based solely on the severity of histologic injury, significant differences in α- and β-diversity were present among gerbils harboring premalignant or malignant lesions compared to gerbils with gastritis alone. This study demonstrates that H. pylori decreases gastric microbial diversity and community structure in a cagA-dependent manner and that as carcinogenesis progresses, there are corresponding alterations in community structure that parallel the severity of disease. IMPORTANCE Microbial communities are essential for the maintenance of human health, and when these communities are altered, hosts can become susceptible to inflammation and disease. Dysbiosis contributes to gastrointestinal cancers, and specific bacterial species are associated with this phenotype. This study uses a robust and reproducible animal model to demonstrate that H. pylori infection induces gastric dysbiosis in a cagA-dependent manner and further that dysbiosis and altered microbial community structure parallel the severity of H. pylori-induced gastric injury. Ultimately, such models of H. pylori infection and cancer that can effectively evaluate multiple determinants simultaneously may yield effective strategies for manipulating the gastric microbiota to prevent the development of gastric cancer.


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