| 1. |
- Henstrom, M., et al.
(författare)
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
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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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| 2. |
- Thorell, Kaisa, 1983, et al.
(författare)
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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
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Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 201:21
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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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| 3. |
- Sundin, Johanna, et al.
(författare)
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Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome
- 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
- Altered bacterial composition and small intestinal bacterial overgrowth (SIBO) may be associated with irritable bowel syndrome (IBS). This study aimed to determine the fecal and mucosa-associated bacterial composition along the gastrointestinal (GI) tract and to assess SIBO in IBS. Bacterial composition of feces, and mucosa of the duodenum and sigmoid colon was determined by 16S rRNA-amplicon-sequencing. SIBO was evaluated by bacterial culture of duodenal aspirate, glucose and lactulose breath tests. Mucosal antibacterial gene expression was assessed by PCR Array. The bacterial profiles of feces and the mucosa of sigmoid colon, but not duodenum, differed between IBS patients (n = 17) and HS (n = 20). The IBS specific bacterial profiles were linked to the colonic antibacterial gene expression. Fecal bacterial profile differed between IBS subtypes, while the mucosa-associated bacterial profile was associated with IBS symptom severity and breath tests results at baseline (H-2 and/or CH4 >= 15 ppm). The prevalence of SIBO was similar between IBS patients and HS. This study demonstrates that alterations in the bacterial composition of the sigmoid colon of IBS patients were linked to symptoms and immune activation. While breath tests reflected the mucosa-associated bacterial composition, there was no evidence for high prevalence of SIBO or small intestinal bacterial alterations in IBS.
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| 4. |
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| 5. |
- 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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| 6. |
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| 7. |
- Forsberg, A., et al.
(författare)
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Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
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Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:6, s. 513-521
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Tidskriftsartikel (refereegranskat)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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| 8. |
- Pammi, Mohan, et al.
(författare)
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Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis : a systematic review and meta-analysis
- 2017
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Ingår i: Microbiome. - : BIOMED CENTRAL LTD. - 2049-2618. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Background: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. Methods and results: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using cultureindependent molecular techniques and reported a and beta-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean +/- SD of 30.1 +/- 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha-or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). Conclusions: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.
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| 9. |
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| 10. |
- Boven, A., et al.
(författare)
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Clostridioides difficile infection, recurrence and the associated healthcare consumption in Sweden between 2006 and 2019 : a population-based cohort study
- 2024
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clostridioides difficile infection (CDI) causes a major burden to individuals and society, yet the impact may vary depending on age, sex, underlying comorbidities and where CDI was acquired (hospital or community). Methods: This Swedish nationwide population-based cohort study (2006–2019) compared all 43,150 individuals with CDI to their 355,172 matched controls (first year and entire follow-up). Negative binomial regression models compared the cumulated length of stay, number of in-hospital admissions, outpatient visits and prescriptions after the first CDI episode expressed as incidence rate ratios (IRR) and 95% confidence intervals for the entire follow-up. Results: Overall, 91.6% of CDI cases were hospital acquired, and 16.8% presented with recurrence(s); 74.8%of cases were ≥ 65 years and 54.2% were women. Compared to individuals without CDI, in-hospital stay rates were 18.01 times higher after CDI (95% CI 17.40–18.63, first-year: 27.4 versus 1.6 days), 9.45 times higher in-hospital admission (95% CI 9.16–9.76, first-year: 2.6 versus 1.3 hospitalisations), 3.94 times higher outpatient visit (95% CI 3.84–4.05, first-year: 4.0 versus 1.9 visits) and 3.39 times higher dispensed prescriptions rates (95% CI 3.31–3.48, first-year: 25.5 versus 13.7 prescriptions). For all outcomes, relative risks were higher among the younger (< 65 years) than the older (≥ 65 years), and in those with fewer comorbidities, but similar between sexes. Compared to those without recurrence, individuals with recurrence particularly showed a higher rate of hospital admissions (IRR = 1.18, 95% 1.12–1.24). Compared to community-acquired CDI, those with hospital-acquired CDI presented with a higher rate of hospital admissions (IRR = 7.29, 95% CI 6.68–7.96) and a longer length of stay (IRR = 7.64, 95% CI 7.07–8.26). Conclusion: CDI was associated with increased health consumption in all affected patient groups. The majority of the CDI burden could be contributed to hospital-acquired CDI (~ 9/10), older patients (~ 3/4) and those with multiple comorbidities (~ 6/10 Charlson score ≥ 3), with 1/5 of the total CDI burden contributed to individuals with recurrence. Yet, relatively speaking the burden was higher among the younger and those with fewer comorbidities, compared to their peers without CDI.
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