| 1. |
- Vaga, S., et al.
(författare)
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Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
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| 2. |
- Rodin, S., et al.
(författare)
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Performance of a 70-mer oligonucleotide microarray for genotyping of Campylobacter jejuni
- 2008
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Campylobacter jejuni is widespread in the environment and is the major cause of bacterial gastroenteritis in humans. In the present study we use microarray-based comparative genomic hybridizations (CGH), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to analyze closely related C. jejuni isolates from chicken and human infection. RESULTS: With the exception of one isolate, the microarray data clusters the isolates according to the five groups determined by PFGE. In contrast, MLST defines only three genotypes among the isolates, indicating a lower resolution. All methods show that there is no inherit difference between isolates infecting humans and chicken, suggesting a common underlying population of C. jejuni. We further identify regions that frequently differ between isolates, including both previously described and novel regions. Finally, we show that genes that belong to certain functional groups differ between isolates more often than expected by chance. CONCLUSION: In this study we demonstrated the utility of 70-mer oligonucleotide microarrays for genotyping of Campylobacter jejuni isolates, with resolution outperforming MLST.
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| 3. |
- Thorpe, H. A., et al.
(författare)
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Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori lives in the human stomach and has a population structure resembling that of its host. However, H. pylori from Europe and the Middle East trace substantially more ancestry from modern African populations than the humans that carry them. Here, we use a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations, implying selection to remove them during admixture. Simulations show that population fitness can be restored after bottlenecks by migration and subsequent admixture of small numbers of bacteria from non-bottlenecked populations. We conclude that recent spread of African DNA has been driven by deleterious mutations accumulated during the original out-of-Africa bottleneck.
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| 4. |
- Andersson, A. F., et al.
(författare)
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Comparative analysis of human gut microbiota by barcoded pyrosequencing
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:7
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Tidskriftsartikel (refereegranskat)abstract
- Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.
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| 5. |
- Jakobsson, H E, et al.
(författare)
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Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:3, s. e9836-
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.
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| 6. |
- Skoglund, A., et al.
(författare)
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Functional analysis of the M.HpyAIV DNA methyltransferase of Helicobacter pylori
- 2007
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Ingår i: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 189:24, s. 8914-8921
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genes encoding restriction-modification (R-M) systems are found in the genome of the human pathogen Helicobacter pylori. R-M genes comprise approximately 10% of the strain-specific genes, but the relevance of having such an abundance of these genes is not clear. The type II methyltransferase (MTase) M.HpyAIV, which recognizes GANTC sites, was present in 60% of the H. pylori strains analyzed, whereof 69% were resistant to restriction enzyme digestion, which indicated the presence of an active MTase. H. pylori strains with an inactive M.HpyAIV phenotype contained deletions in regions of homopolymers within the gene, which resulted in premature translational stops, suggesting that M.HpyAIV may be subjected to phase variation by a slipped-strand mechanism. An M.HpyAIV gene mutant was constructed by insertional mutagenesis, and this mutant showed the same viability and ability to induce interleukin-8 in epithelial cells as the wild type in vitro but had, as expected, lost the ability to protect its self-DNA from digestion by a cognate restriction enzyme. The M.HpyAIV from H. pylori strain 26695 was overexpressed in Escherichia coli, and the protein was purified and was able to bind to DNA and protect GANTC sites from digestion in vitro. A bioinformatic analysis of the number of GANTC sites located in predicted regulatory regions of H. pylori strains 26695 and J99 resulted in a number of candidate genes. katA, a selected candidate gene, was further analyzed by quantitative real-time reverse transcription-PCR and shown to be significantly down-regulated in the M.HpyAIV gene mutant compared to the wild-type strain. This demonstrates the influence of M.HpyAIV methylation in gene expression.
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| 7. |
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| 8. |
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| 9. |
- Olsson, Lisa M., 1984, et al.
(författare)
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Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden
- 2022
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Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 30:5
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Tidskriftsartikel (refereegranskat)abstract
- Temporal dynamics of the gut microbiota potentially limit the identification of microbial features associated with health status. Here, we used whole-genome metagenomic and 16S rRNA gene sequencing to characterize the intra- and inter-individual variations of gut microbiota composition and functional potential of a disease-free Swedish population (n = 75) over one year. We found that 23% of the total compositional variance was explained by intra-individual variation. The degree of intra-individual compositional variability was negatively associated with the abundance of Faecalibacterium prausnitzii (a butyrate producer) and two Bifidobacterium species. By contrast, the abundance of facultative anaerobes and aerotolerant bacteria such as Escherichia coli and Lactobacillus acidophilus varied extensively, independent of compositional stability. The contribution of intra-individual variance to the total variance was greater for functional pathways than for microbial species. Thus, reliable quantification of microbial features requires repeated samples to address the issue of intra-individual variations of the gut microbiota.
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| 10. |
- West, Christina E., et al.
(författare)
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Gut microbiome and innate immune response patterns in IgE-associated eczema
- 2015
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 45:9, s. 1419-1429
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Tidskriftsartikel (refereegranskat)abstract
- Background Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signaling. Objective We examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5 years in predisposed children due to maternal atopy [www.anzctr.org.au, trial ID ACTRN12606000280505]. Methods Microbial composition and diversity were analyzed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1 week, 1 month and 12 months in infants (n=10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5 years of age (n=10). Microbiome data at 1 week and 1 month were analyzed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6 months of age. Results The relative abundance of Gram-positive Ruminococcaceae was lower at 1 week of age in infants developing IgE-associated eczema, compared with controls (p=0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, p=0.042) and TNF-α (-0.597, p=0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4 induced TNF-α (rs= -0.629, p=0.024). This relationship persisted at 1 month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Protebacteria phylum) and TLR4 induced TNF-α (rs=-0.697, p=0.038) and Enterobacteriaceae and IL-6 (rs=-0.709, p=0.035). Mothers whose infants developed IgE-associated eczema had lower α-diversity of Bacteroidetes (p=0.04) although this was not seen later in their infants. At 1 year, α-diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (p=0.002). Conclusion and clinical relevance Our findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated inflammatory cytokine responses to TLR ligands and subsequent development of IgE-associated eczema. This article is protected by copyright. All rights reserved.
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