Response of Gastric Epithelial Progenitors to Helicobacter pylori Isolates Obtained from Swedish Patients with Chronic Atrophic Gastritis

Giannakis, Marios; Bäckhed, Helene Kling; Chen, Swaine L.; Faith, Jeremiah J.; Wu, Meng; Guruge, Janaki L.; Engstrand, Lars; Gordon, Jeffrey I.

doi:10.1074/jbc.m109.052738

Cited by 27 publications

(29 citation statements)

References 64 publications

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“…For if environmental influences were responsible they would have to have operated in childhood, and it is difficult to believe that the fathers have been equally subjected to the same influences in their childhood". In light of our current knowledge of the persistence and familial transmission of H. pylori (23,(54)(55)(56)(57), an increased incidence in peptic ulcer disease across two generations can just as easily be ascribed to transmission of a pathogenic strain as it can to the genetic origins suggested by Doll and Buch.…”

Section: A Model Of Microbial Inheritancementioning

confidence: 99%

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Faith¹,

Colombel

Gordon

2015

Proc. Natl. Acad. Sci. U.S.A.

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It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases.microbial inheritance | strain-resolution human microbial ecology analyses | effector strains | health | disease

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Section: A Model Of Microbial Inheritancementioning

confidence: 99%

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Faith¹,

Colombel

Gordon

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…S3) into "operational gene units" (OGUs), a term we use in a way that is analogous to OTUs. If any predicted gene from an assembled genome was present in a given OGU bin, that OGU was called "present" within that genome (43). Functions were assigned to predicted proteins encoded by each gene by using the KEGG and STRING databases; Pfam and TIGRFAM annotations were also made.…”

Section: Mz Twins Have Higher Concordance For Gut Methanogens Than Dzmentioning

confidence: 99%

Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii , studied in twins

Hansen

Lozupone

Rey

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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192

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The human gut microbiota harbors three main groups of H 2 -consuming microbes: methanogens including the dominant archaeon, Methanobrevibacter smithii, a polyphyletic group of acetogens, and sulfate-reducing bacteria. Defining their roles in the gut is important for understanding how hydrogen metabolism affects the efficiency of fermentation of dietary components. We quantified methanogens in fecal samples from 40 healthy adult female monozygotic (MZ) and 28 dizygotic (DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M. smithii strains isolated from families of MZ and DZ twins, and performed RNA-Seq of a subset of strains to identify their responses to varied formate concentrations. The concordance rate for methanogen carriage was significantly higher for MZ versus DZ twin pairs. Co-occurrence analysis revealed 22 bacterial specieslevel taxa positively correlated with methanogens: all but two were members of the Clostridiales, with several being, or related to, known hydrogen-producing and -consuming bacteria. The M. smithii pan-genome contains 987 genes conserved in all strains, and 1,860 variably represented genes. Strains from MZ and DZ twin pairs had a similar degree of shared genes and SNPs, and were significantly more similar than strains isolated from mothers or members of other families. The 101 adhesin-like proteins (ALPs) in the pan-genome (45 ± 6 per strain) exhibit strain-specific differences in expression and responsiveness to formate. We hypothesize that M. smithii strains use their different repertoires of ALPs to create diversity in their metabolic niches, by allowing them to establish syntrophic relationships with bacterial partners with differing metabolic capabilities and patterns of co-occurrence.hydrogen-consuming microbes | metagenomics | microbial genome evolution | horizontal gene tranfer H uman microbiome projects seek to determine how microbial communities are assembled, maintained, and operate within our various body habitats as a function of our different cultural and socioeconomic conditions, family structures, stages of life, genotypes, and physiologies. Culture-independent metagenomic surveys have revealed that microbial communities cluster according to body habitat but with considerable interpersonal variation in bacterial species content (1), although differences are smaller within rather than between families (2). The gut harbors our largest collection of microbes, spanning all three domains of life. Bacteria dominate, specifically members of the phyla Bacteroidetes and Firmicutes (2-5).Monozygotic (MZ) and dizygotic (DZ) twin pairs provide an attractive study paradigm for dissecting the relative contributions of host genotype and environmental exposures to shaping the microbial and viral landscape of our gut microbiota (2, 6). To date, bacterial 16S rRNA datasets indicate that adult MZ co-twins share no more similarity in their fecal bacterial communities than DZ ...

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“…Since hopZ has previously been shown to confer a selective advantage in a mouse model of chronic atrophic gastritis (20), we asked whether the hopZ status might correlate with the development of chronic atrophic gastritis in humans. We sequenced hopZ in 63 isolates from the Kalixanda study, a large population-based study S3 and Table S5 in the supplemental material).…”

Section: Hopz Status In H Pylori Isolates From Patients With Chronicmentioning

confidence: 99%

“…In addition to its regulation via the phase-variable repeat, hopZ has also been reported to be regulated at the transcriptional level in response to changing pH (41) and to contact with host cells (20). In this study, we systematically investigated phase and sequence variability in hopZ during acute and chronic infection of humans and after transmission, as well as the association of hopZ with the phylogeny of H. pylori.…”

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confidence: 99%

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In Vivo Sequence Variation in HopZ, a Phase-Variable Outer Membrane Protein of Helicobacter pylori

et al. 2012

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The Helicobacter pylori outer membrane protein HopZ is regulated by a phase-variable CT repeat and occurs in two distinct allelic variants. Whole-genome comparisons of isolates from one human volunteer recently provided evidence for in vivo selection for the hopZ ON status. We explored the frequency of sequence variation in hopZ during acute and chronic human infection and studied the association of hopZ with the phylogeographic population structure of H. pylori. hopZ ON variants were cultured from 24 out of 33 volunteers challenged with the hopZ OFF strain BCS 100. Transmission of H. pylori within families was also frequently associated with a status change of hopZ. In contrast, hopZ sequences obtained from 26 sets of sequential isolates from chronically infected individuals showed no changes of status, suggesting that the hopZ status selected during early infection is subsequently stable. Mutations leading to amino acid changes in HopZ occurred more frequently in ON than in OFF status isolates during chronic infection, indicating that sequence changes are more likely the result of positive selection in ON isolates than of a loss of negative selection pressure in OFF isolates. Analysis of 63 isolates from chronically infected individuals revealed no significant correlation of hopZ status with chronic atrophic gastritis. hopZ sequences were obtained from a globally representative collection of 54 H. pylori strains. All H. pylori populations contained hopZ-positive isolates. The data suggest that hopZ has been acquired and split into the two variants before the human migration out of Africa.

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Response of Gastric Epithelial Progenitors to Helicobacter pylori Isolates Obtained from Swedish Patients with Chronic Atrophic Gastritis

Cited by 27 publications

References 64 publications

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii , studied in twins

In Vivo Sequence Variation in HopZ, a Phase-Variable Outer Membrane Protein of Helicobacter pylori

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