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1.
  • Thorell, Kaisa, et al. (författare)
  • Isolates from Colonic Spirochetosis in Humans Show High Genomic Divergence and Potential Pathogenic Features but Are Not Detected Using Standard Primers for the Human Microbiota
  • 2019
  • Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 201:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Colonic spirochetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance, and only a few bacterial isolates from this condition have been characterized to date. In a randomized, population-based study in Stockholm, Sweden, 745 healthy individuals underwent colonoscopy with biopsy sampling. Of these individuals, 17 (2.3%) had colonic spirochetosis, which was associated with eosinophilic infiltration and a 3-fold-increased risk for irritable bowel syndrome (IBS). We aimed to culture the bacteria and perform whole-genome sequencing of the isolates from this unique representative population sample. From 14 out of 17 individuals with spirochetosis we successfully isolated, cultured, and performed whole-genome sequencing of in total 17 isolates, including the Brachyspira aalborgi type strain, 513A. Also, 16S analysis of the mucosaassociated microbiota was performed in the cases and nonspirochetosis controls. We found one isolate to be of the species Brachyspira pilosicoli; all remaining isolates were of the species Brachyspira aalborgi. Besides displaying extensive genetic heterogeneity, the isolates harbored several mucin-degrading enzymes and other virulenceassociated genes that could confer a pathogenic potential in the human colon. We also showed that 16S amplicon sequencing using standard primers for human microbiota studies failed to detect Brachyspira due to primer incompatibility. IMPORTANCE This is the first report of whole-genome analysis of clinical isolates from individuals with colonic spirochetosis. This characterization provides new opportunities in understanding the physiology and potentials of these bacteria that densely colonize the gut in the individuals infected. The observation that standard 16S amplicon primers fail to detect colonic spirochetosis may have major implications for studies searching for associations between members of the microbiota and clinical conditions such as irritable bowel syndrome (IBS) and should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.
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2.
  • Vaga, S., et al. (författare)
  • Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
  • 2020
  • Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10:1
  • 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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3.
  • Agréus, Lars, et al. (författare)
  • Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community
  • 2016
  • Ingår i: United European Gastroenterology journal. - 2050-6406 .- 2050-6414. ; 4:5, s. 686-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.
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4.
  • Henstrom, M., et al. (författare)
  • Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
  • 2018
  • Ingår i: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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5.
  • Hugerth, Luisa W., et al. (författare)
  • No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population
  • 2020
  • Ingår i: Gut. - 0017-5749 .- 1468-3288. ; 69:6, s. 1076-1084
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings.Design The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases).Results While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R-2=0.255, p<3E-11) as was diversity (R-2=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals.Conclusions No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.
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6.
  • Walker, Marjorie M., et al. (författare)
  • Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden
  • 2015
  • Ingår i: Human Pathology. - 0046-8177 .- 1532-8392. ; 46:2, s. 277-283
  • Tidskriftsartikel (refereegranskat)abstract
    • Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (p = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.
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7.
  • Abrahamsson, T. R., et al. (författare)
  • Low gut microbiota diversity in early infancy precedes asthma at school age
  • 2014
  • Ingår i: Clinical and Experimental Allergy. - : Wiley-Blackwell. - 0954-7894 .- 1365-2222. ; 44:6, s. 842-850
  • 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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8.
  • Andersson, A. F., et al. (författare)
  • Comparative analysis of human gut microbiota by barcoded pyrosequencing
  • 2008
  • Ingår i: PLoS ONE. - 1932-6203. ; 3:7
  • 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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9.
  • Aro, Pertti, et al. (författare)
  • Use of tobacco products and gastrointestinal morbidity : an endoscopic population-based study (the Kalixanda study)
  • 2010
  • Ingår i: European Journal of Epidemiology. - 0393-2990 .- 1573-7284. ; 25:10, s. 741-750
  • 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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10.
  • Bugaytsova, Jeanna A., et al. (författare)
  • Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence
  • 2017
  • Ingår i: Cell Host and Microbe. - : CELL PRESS. - 1931-3128 .- 1934-6069. ; 21:3, s. 376-389
  • Tidskriftsartikel (refereegranskat)abstract
    • The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.
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