Exploring the impact of Helicobacter pylori on gut microbiome composition.
ABSTRACT: Helicobacter pylori (H. pylori) is known to colonize gastric mucosa, induce inflammation, and alter gastric microbiota resulting in a spectrum of gastric diseases. Likewise, changes in gut microbiota have recently been linked with various metabolic and inflammatory diseases. While extensive number of studies were published examining the relationship between H. pylori and gastric microbiota, little is known about the impact of H. pylori on downstream gut microbiota. In this study, we performed 16 S rRNA and ITS2-based microbial profiling analysis of 60 stool samples from adult individuals. Remarkably, the gut microbiota of H. pylori infected individuals was shown to be increased of members belonging to Succinivibrio, Coriobacteriaceae, Enterococcaceae, and Rikenellaceae. Moreover, gut microbiota of H. pylori infected individuals was shown to have increased abundance of Candida glabrata and other unclassified Fungi. These results links possible role for H. pylori-associated changes in the gut microbiota in intestinal mucosal barrier disruption and early stage colorectal carcinoma deployment. Altogether, the identified differences in bacterial and fungal composition provides important information that may eventually lead to the development of novel biomarkers and more effective management strategies.
Project description:BACKGROUND:H. pylori infection and eradication cause perturbations of the gut microbiome. The gut microbiota has been identified as a potential contributor to metabolic diseases. We evaluate whether these alterations in intestinal microbiota composition produced by H. pylori infection and its posterior eradication with antibiotic treatment could be associated with glucose homeostasis in metabolically healthy subjects. METHODS:Forty adult patients infected with H. pylori and 20 control subjects were recruited. The infected subjects were evaluated before and two months after eradication treatment (omeprazole, clarithromycin, amoxicillin). The microbiota composition in fecal samples was determined by 16S rRNA gene (V3-V4) sequencing using Illumina Miseq. RESULTS:Patients (pre- and post-H. pylori eradication) showed a decreased bacterial richness and diversity with respect to controls. There was an improvement in glucose homeostasis in subjects two months after H. pylori eradication treatment. Changes in the amount of Rikenellaceae, Butyricimonas, E. biforme, B. fragilis, and Megamonas were inversely associated with changes in the glucose level or related parameters (Hb1ac) in H. pylori eradication subjects. CONCLUSIONS:H. pylori infection and eradication with antibiotic treatment causes alteration of the human gut microbiome. The increase in SCFA-producing bacteria and glucose-removing bacteria, specifically members of Megamonas, Rikenellaceae and Butyricimonas, has been related with an improvement in glucose homeostasis after H. pylori eradication with antibiotic treatment.
Project description:<i>Helicobacter pylori</i> infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most <i>H. pylori</i>-infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the <i>H. pylori</i>-associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to <i>H. pylori</i> infection and related gastric diseases. Here, we studied <i>H. pylori</i> infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents (<i>N</i> = 375) in southwestern India by standard <i>H. pylori</i> culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent <i>H. pylori</i> strains (<i>vacAs1i1m1cagA</i>+) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the <i>H. pylori</i>-infected vs. <i>H. pylori</i>-non-infected individuals. <i>Bifidobacterium</i> (belonging to the phylum Actinobacteria) and <i>Bacteroides</i> (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the <i>H. pylori</i>+ group than the <i>H. pylori</i>- group (<i>p</i> < 0.05). On the contrary, for the <i>H. pylori</i>+ group, genus <i>Dialister</i> (bacteria belonging to the phylum Firmicutes) and genus <i>Prevotella</i> (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the <i>H. pylori-</i> group (<i>p</i> < 0.05). Notably, those who carried <i>H. pylori</i> in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance (<i>p</i> < 0.05) of several <i>Bifidobacterium</i> species (e.g., <i>B. adolescentis</i>, <i>B. longum</i>) in the lower gut suggesting a protective role of <i>Bifidobacterium</i>. Our results show the link between lower gastrointestinal microbes and upper gastrointestinal diseases. Moreover, the results are important for developing effective probiotic and early prognosis of severe gastric diseases.
Project description:Both maternal microbiota and helminth infection may alter offspring immunity but the relationship between these is underexplored. We hypothesized that maternal helminth exposure prior to pregnancy has lasting consequences on offspring intestinal microbiota and consequent immunity. Female BALB/c adult mice were infected with 500L3 Nippostrongylus brasiliensis (N brasiliensis). Infection was cleared by ivermectin treatment, and mice were mated 3 weeks post-infection (NbM). Control mice were not infected but were exposed to ivermectin (NvM). We analysed maternal gut microbiota during pregnancy, breastmilk microbiota and offspring faecal microbiota and immunity 2 weeks after delivery. During pregnancy, NbM (Mothers previously infected with Nippostrongylus brasiliensis) displayed significantly altered stool bacterial communities (R<sup>2</sup> = .242; P = .001), with increased abundance of Enterococcaceae versus NvM (Naive mothers). Similarly, we observed a profound impact on breastmilk microbiota in NbM vs NvM. Moreover, NbM pups showed significantly altered gut microbial communities at 14 days of age versus those born to NvM with increased relative abundance of Coriobacteriaceae and Micrococcaceae. These changes were associated with alterations in pup immunity including increased frequencies and numbers of activated CD4 T cells (CD4 + CD44hi) in NbM offspring spleens. Taken together, we show that preconception helminth infections impact offspring immunity possibly through alteration of maternal and offspring microbiota.
Project description:Helicobacter pylori have been shown to influence physiological regulation of metabolic hormones involved in food intake, energy expenditure and body mass. It has been proposed that inducing H. pylori-induced gastric atrophy damages hormone-producing endocrine cells localized in gastric mucosal layers and therefore alter their concentrations. In a recent study, we provided additional proof in mice under controlled conditions that H. pylori and gut microbiota indeed affects circulating metabolic gut hormones and energy homeostasis. In this addendum, we presented data from follow-up investigations that demonstrated H. pylori and gut microbiota-associated modulation of metabolic gut hormones was independent and precedes H. pylori-induced histopathological changes in the gut of H. pylori-infected mice. Thus, H. pylori-associated argumentation of energy homeostasis is not caused by injury to endocrine cells in gastric mucosa.
Project description:Human milk fat contains high concentrations of medium-chained fatty acids (MCFA) and triacylglycerols emulsified by a sphingomyelin-rich phospholipid membrane (milk phospholipids, MPL). Infant formula comprises mainly long-chained fatty acids (LCFA) emulsified with dairy proteins and soy lecithin (SL) lacking sphingomyelin. Sphingomyelin content and saturation level of phospholipids affect the gut lipase activity, which alters the concentrations of lipid hydrolysis products in ileum and colon, and hereby putatively affects the competitive advantage of specific gut bacteria. Thus, differences in phospholipid and FA composition may modulate the establishment of the gut microbiota. We investigated effects of fatty acid (FA) composition and emulsification (MPL vs SL) ingested during establishment of human gut microbiota in germ-free mice, and found that cecal microbiotas from mice given MCFA-rich emulsions were characterized by high relative abundances of Bacteroidaceae and Desulfovibrionaceae, while LCFA-rich emulsions caused higher abundances of Enterobacteriaceae, Erysipelotrichaceae, Coriobacteriaceae and Enterococcaceae. Consumption of SL-emulsified lipids skewed the community towards more Enterococcaceae and Enterobacteriaceae, while MPL increased Bacteroidaceae, Desulfovibrionaceae, Rikkenellaceae and Porphyromonadaceae. Intake of SL increased cecal concentrations of iso-valeric and iso-butyric acids. This suggests that fat-type and emulsifiers applied in infant formula may have distinct effects on the establishment of the gut microbiota in formula-fed infants.
Project description:Changes in the intestinal microbial community and some metabolic disturbances, including obesity and type2 diabetes, are related. Glucagon-like peptide-1 (GLP-1) regulates glucose homeostasis. Microbiota have been linked to incretin secretion. Antibiotic use causes changes in microbial diversity and composition. Our aim was to evaluate the relationship between microbiota changes and GLP-1 secretion. A prospective case-control study with a Helicobacter pylori-positive patient model involving subjects under eradication therapy (omeprazole, clarithromycin, and amoxicillin). Forty patients with H. pylori infection and 20 matched participants, but negative for H. pylori antigen. Patients were evaluated before and two months after treatment. We analyzed anthropometric measurements, carbohydrate metabolism, lipid profile, and C-reactive protein. Gut microbiota composition was analyzed through 16S rRNA amplicon sequencing (IlluminaMiSeq). Eradication treatment for H. pylori decreased bacterial richness (Chao1, p = 0.041). Changes in gut microbiota profiles were observed at phylum, family, genus and species levels. GLP-1 secretion and variables of carbohydrate metabolism were improved. Correlations were seen between GLP-1 changes and variations within microbial community abundances, specifically Bifidobacterium adolescentis, the Lachnobacterium genus, and Coriobacteriaceae family. A conventional treatment to eradicate H. pylori could improve carbohydrate metabolism possibly in relation with an increase in GLP-1 secretion. GLP-1 secretion may be related to alterations in intestinal microbiota, specifically Lachnobacterium, B. adolescentis and Coriobacteriaceae.
Project description:Emerging evidence shows that the human microbiota plays a larger role in disease progression and health than previously anticipated. Helicobacter pylori, the causative agent of gastric cancer and duodenal and gastric ulcers, was early associated with gastric disease, but it has also been proposed that the accompanying microbiota in Helicobacter pylori-infected individuals might affect disease progression and gastric cancer development. In this study, the composition of the transcriptionally active microbial community and H. pylori gene expression were determined using metatranscriptomic RNA sequencing of stomach biopsy specimens from individuals with different H. pylori infection statuses and premalignant tissue changes. The results show that H. pylori completely dominates the microbiota not only in infected individuals but also in most individuals classified as H. pylori uninfected using conventional methods. Furthermore, H. pylori abundance is positively correlated with the presence of Campylobacter, Deinococcus, and Sulfurospirillum Finally, we quantified the expression of a large number of Helicobacter pylori genes and found high expression of genes involved in pH regulation and nickel transport. Our study is the first to dissect the viable microbiota of the human stomach by metatranscriptomic analysis, and it shows that metatranscriptomic analysis of the gastric microbiota is feasible and can provide new insights into how bacteria respond in vivo to variations in the stomach microenvironment and at different stages of disease progression.
Project description:<b>Background:</b> The gut microbiome plays an important role in the lipid metabolism. Antibiotic treatment causes changes in the intestinal microbiota. Our objective was to explore the relationship between changes in the intestinal microbiota and the level of plasma high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL). <b>Methods:</b> Prospective case-control study with <i>Helicobacter pylori</i>-positive patients undergoing eradication therapy with omeprazole, clarithromycin, and amoxicillin. Stool and blood samples were obtained from 20 controls (<i>H. pylori</i> negative) and 40 patients before and 2 months after antibiotic treatment. Gut microbiota was determined through 16S rRNA amplicon sequencing (Illumina MiSeq). <b>Results:</b> Eradication treatment for <i>H. pylori</i> increased the HDL levels, and caused changes in gut microbiota profiles. An unfavorable lipid profiles (high LDL and low HDL levels) was associated with a low microbial richness and an increase of the Bacteroidetes phylum. <i>Prevotella copri, Lachonobacterium</i>, and <i>Delsufovibrio</i> were positively associated with HDL while <i>Rikenellaceae</i> was negatively associated with HDL after completing antibiotic treatment. <b>Conclusions:</b> <i>Helicobacter pylori</i> eradication treatment could improve lipid metabolism in relation with an increase in the HDL. Changes in the abundance of specific bacteria, such as <i>P. copri, Lachonobacterium, Delsufovibrio</i>, and <i>Rikenellaceae</i> could be associated with change in the plasma HDL levels.
Project description:Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (<i>n</i> = 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. β-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered β-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery. <b>IMPORTANCE</b> The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.
Project description:Helicobacter pylori is a causative pathogen of many gastric and extra-gastric diseases. It has infected about half of the global population. There were no genome-wide association studies (GWAS) for H. pylori infection conducted in Chinese population, who carried different and relatively homogenous strain of H. pylori. In this work, we performed SNP (single nucleotide polymorphism)-based, gene-based and pathway-based genome-wide association analyses to investigate the genetic basis of host susceptibility to H. pylori infection in 480 Chinese individuals. We also profiled the composition and function of the gut microbiota between H. pylori infection cases and controls. We found several genes and pathways associated with H. pylori infection (P < 0.05), replicated one previously reported SNP rs10004195 in TLR1 gene region (P = 0.02). We also found that glycosaminoglycan biosynthesis related pathway was associated with both onset and progression of H. pylori infection. In the gut microbiome association study, we identified 2 species, 3 genera and several pathways had differential abundance between H. pylori infected cases and controls. This paper is the first GWAS for H. pylori infection in Chinese population, and we combined the genetic and microbial data to comprehensively discuss the basis of host susceptibility to H. pylori infection.