| 1. |
- Aro, Pertti, et al.
(författare)
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Use of tobacco products and gastrointestinal morbidity : an endoscopic population-based study (the Kalixanda study)
- 2010
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 25:10, s. 741-750
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Tidskriftsartikel (refereegranskat)abstract
- The impact of snus (smokeless tobacco or snuff) on gastrointestinal symptoms and pathological findings is largely unknown. The authors aimed to investigate whether the exposure to different forms of tobacco influences upper gastrointestinal symptoms, histology and frequency of Helicobacter pylori infection. A random sample (n = 2,860) of the adult population of two northern Swedish municipalities Kalix and Haparanda (n = 21,610) was surveyed between December 1998 and June 2001 using a validated postal questionnaire assessing gastrointestinal symptoms (response rate 74.2%, n = 2,122) (The Kalixanda Study). A random sub-sample (n = 1,001) of the responders was invited to undergo an esophagogastroduodenoscopy (participation rate 73.3%) including biopsies, Helicobacter pylori culture and serology and symptom assessment and exploration of present and past use of tobacco products. No symptom groups were associated with snus use. Snus users had a significantly higher prevalence of macroscopic esophagitis univariately but snus use was not associated with esophagitis in multivariate analysis. Snus use was associated with basal cell hyperplasia (OR = 1.74, 95% CI: 1.02, 3.00) and with elongation of papillae (OR = 1.79, 95% CI: 1.05-3.05) of the squamous epithelium at the esophago-gastric junction. Current smoking cigarettes was associated with overall peptic ulcer disease (OR = 2.32, 95% CI: 1.04, 5.19) whereas snus use was not. There were no significant association between current Helicobacter pylori infection and different tobacco product user groups. Snus significantly alters the histology of the distal esophagus but does not impact on gastrointestinal symptoms or peptic ulcer disease.
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| 2. |
- Lu, Jun, et al.
(författare)
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Inhibition of Bacterial Thioredoxin Reductase: An Antibiotic Mechanism Targetting Bacteria Lacking Glutathione
- 2013
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 27:4, s. 1394-1403
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Tidskriftsartikel (refereegranskat)abstract
- Increasing antibiotic resistance makes the identification of new antibacterial principles an urgent task. The thioredoxin system including thioredoxinreductase (TrxR), thioredoxin (Trx), and NADPH plays critical roles in cellular DNA synthesis and defense against oxidative stress. Notably, TrxR is very different in structure and mechanism in mammals and bacteria. Ebselen [2-phenyl-1,2 benzisoselenazol-3(2H)-one], a well-known antioxidant and a substrate for mammalian TrxR and Trx, is rapidly bacteriocidal for methicillin-resistant Staphylococcus aureus by an unknown mechanism. We have discovered that ebselen is a competitive inhibitor of Escherichia coli TrxR with a K-i of 0.52 +/- 0.13 mu M, through reaction with the active site dithiol of the enzyme. Bacteria lacking glutathione (GSH) and glutaredoxin, in which TrxR and Trx are essential for DNA synthesis, were particularly sensitive to ebselen. In growth-inhibited E. coli strains, Trx1 and Trx2 were oxidized, demonstrating that electron transfer via thioredoxin was blocked. Ebselen and its sulfur analog ebsulfur were bactericidal for GSH-negative pathogens. Ebsulfur inhibited a clinically isolated Helicobacter pylori strain with a minimum inhibitory concentration value as low as 0.39 mu g/ml. These results demonstrate that bacterial Trx and TrxR are viable antibacterial drug targets using benzisoselenazol and benzisothiazol derivates.-Lu, J., Vlamis-Gardikas, A., Kandasamy, K., Zhao, R., Gustafsson, T. N., Engstrand, L., Hoffner, S., Engman, L., Holmgren, A. Inhibition of bacterial thioredoxin reductase: an antibiotic mechanism targeting bacteria lacking glutathione.
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| 3. |
- Normann, Erik, et al.
(författare)
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Intestinal microbial profiles in extremely preterm infants with and without necrotizing enterocolitis
- 2013
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 102:2, s. 129-136
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Tidskriftsartikel (refereegranskat)abstract
- Aim Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants. The suggested role of intestinal microbiota in the development of NEC needs to be elucidated. Methods This prospective single-centre casecontrol study applied barcoded pyrosequencing to map the bacterial composition of faecal samples from extremely preterm infants. Ten patients were diagnosed with NEC and matched to healthy controls with regard to sex, gestational age and mode of delivery prior to analysis of the samples. Results Enterococcus, Bacillales and Enterobacteriaceae dominated the flora. Although not statistically significant, a high relative abundance of Bacillales and Enterobacteriaceae was detected at early time points in patients developing NEC, while healthy controls had a microbiota more dominated by Enterococcus. A low diversity of intestinal microbial flora was found without any differences between NEC patients and controls. In 16 healthy controls, Firmicutes (Enterococcus and Bacillales) dominated the faecal flora during the first weeks after birth and were then succeeded by Enterobacteriaceae. Conclusion No significant differences in the composition of intestinal microbiota of patients developing NEC were detected; however, some findings need to be scrutinized in subsequent studies.
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| 4. |
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| 5. |
- Abrahamsson, Thomas, et al.
(författare)
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Low diversity of the gut microbiota in infants with atopic eczema
- 2012
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Ingår i: Journal of Allergy and Clinical Immunology. - New York, USA : Elsevier BV. - 0091-6749 .- 1097-6825. ; 129:2, s. 434-U244
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. OBJECTIVE: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P= .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P= .02 and P= .01) and the phylum Proteobacteria at 12 months of age (P= .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P= .008, q= 0.02). CONCLUSION: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.
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| 6. |
- Abrahamsson, Thomas, et al.
(författare)
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Low gut microbiota diversity in early infancy precedes asthma at school age
- 2014
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:6, s. 842-850
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Tidskriftsartikel (refereegranskat)abstract
- Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.
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| 7. |
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| 8. |
- Andres, Sonke, et al.
(författare)
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Type I Restriction-Modification Loci Reveal High Allelic Diversity in Clinical Helicobacter pylori Isolates
- 2010
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 15:2, s. 114-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: A remarkable variety of restriction-modification (R-M) systems is found in Helicobacter pylori. Since they encompass a large portion of the strain-specific H. pylori genes and therefore contribute to genetic variability, they are suggested to have an impact on disease outcome. Type I R-M systems comprise three different subunits and are the most complex of the three types of R-M systems. Aims: We investigated the genetic diversity and distribution of type I R-M systems in clinical isolates of H. pylori. Material and methods: Sixty-one H. pylori isolates from a Swedish hospital based case-control study and 6 H. pylori isolates of a Swedish population-based study were analyzed using polymerase chain reaction for the presence of the three R-M systems' subunits. Representative gene variants were sequenced. Results: Although the hsdM and hsdR genes appeared conserved in our clinical H. pylori isolates, the sequences of the hsdS loci were highly variable. Despite their sequence diversity, the genes per se were present at high frequencies. We identified a number of novel allelic hsdS variants, which are distinct from corresponding hsdS loci in the sequenced H. pylori strains 26695, J99 and HPAG1. In analyses of paired H. pylori isolates, obtained from the same individuals with a 4-year interval, we observed genetic modifications of hsdS genes in patients with atrophic gastric mucosa. Discussion: We propose that the genetic variability of hsdS genes in a bacterial population will give rise to new specificities of these enzymes, which might lead to adaptation to an ever-changing gastric environment.
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| 9. |
- Basmarke-Wehelie, Rahma, et al.
(författare)
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The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
- 2011
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Ingår i: Gastroenterology. - Baltimore : Elsevier BV. - 0016-5085 .- 1528-0012. ; 141:3, s. 918-928
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.
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| 10. |
- Dicksved, Johan, et al.
(författare)
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Susceptibility to Campylobacter Infection Is Associated with the Species Composition of the Human Fecal Microbiota
- 2014
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Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 5:5, s. e01212-14-
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after natural Campylobacter infection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season of Campylobacter infection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive for Campylobacter and those who remained negative. Individuals who became Campylobacter positive had a significantly higher abundance of Bacteroides (P = 0.007) and Escherichia (P = 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance of Phascolarctobacterium (P = 0.017) and Streptococcus (P = 0.034) sequences than the Campylobacter-negative group, which had an overrepresentation of Clostridiales (P = 0.017), unclassified Lachnospiraceae (P = 0.008), and Anaerovorax (P = 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time in Campylobacter-negative participants, but significant long-term changes were found in the Campylobacter-positive group (P < 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance to Campylobacter colonization in humans and that Campylobacter infection can have long-term effects on the composition of the human fecal microbiota. IMPORTANCE Studies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances of Escherichia coli and Bacteroides species have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general and Campylobacter infection in particular. In this study, we assessed the role of the human gut microbiota in resistance to Campylobacter colonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive for Campylobacter. As their microbiotas were characterized by high abundances of Bacteroides spp. and E. coli, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.
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