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  • 1
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    Online Resource
    Consistent alterations in faecal microbiomes of patients with primary sclerosing cholangitis independent of associated colitis
    Wiley ; 2019
    In:  Alimentary Pharmacology & Therapeutics Vol. 50, No. 5 ( 2019-09), p. 580-589
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 50, No. 5 ( 2019-09), p. 580-589
    Abstract: Single‐centre studies reported alterations of faecal microbiota in patients with primary sclerosing cholangitis (PSC). As regional factors may affect microbial communities, it is unclear if a microbial signature of PSC exists across different geographical regions. Aim To identify a robust microbial signature of PSC independent of geography and environmental influences. Methods We included 388 individuals (median age, 47 years; range, 15‐78) from Germany and Norway in the study, 137 patients with PSC (n = 75 with colitis), 118 with ulcerative colitis (UC) and 133 healthy controls. Faecal microbiomes were analysed by 16S rRNA gene sequencing (V1‐V2). Differences in relative abundances of single taxa were subjected to a meta‐analysis. Results In both cohorts, microbiota composition (beta‐diversity) differed between PSC patients and controls ( P   〈  0.001). Random forests classification discriminated PSC patients from controls in both geographical cohorts with an average area under the curve of 0.88. Compared to healthy controls, many new cohort‐spanning alterations were identified in PSC, such as an increase of Proteobacteria and the bile‐tolerant genus Parabacteroides , which were detected independent from geographical region. Associated colitis only had minor effects on microbiota composition, suggesting that PSC itself drives the faecal microbiota changes observed. Conclusion Compared to healthy controls, numerous microbiota alterations are reproducible in PSC patients across geographical regions, clearly pointing towards a microbiota composition that is shaped by the disease itself and not by environmental factors. These reproducibly altered microbial populations might provide future insights into the pathophysiology of PSC.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v50.5
    DOI: 10.1111/apt.15375
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 2
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    A disease‐specific decline of the relative abundance of Bifidobacterium in patients with autoimmune hepatitis
    Wiley ; 2020
    In:  Alimentary Pharmacology & Therapeutics Vol. 51, No. 12 ( 2020-06), p. 1417-1428
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 51, No. 12 ( 2020-06), p. 1417-1428
    Abstract: The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH. Aim To investigate disease‐specific microbiome alterations in AIH. Methods The V1‐V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy controls (HC) n = 95, primary biliary cholangitis (PBC) n = 99 and ulcerative colitis (UC) n = 81). Results Biodiversity (Shannon entropy) was decreased in AIH patients compared to HC ( P  = 0.016), which was partially reversed by azathioprine ( P  = 0.011). Regarding between‐sample diversity, AIH patients separated from HC, PBC and UC individuals (all P  = 0.001). Compared to HC, decreased relative abundance of anaerobic genera such as Faecalibacterium and an increase of Veillonella and the facultative anaerobic genera Streptococcus and Lactobacillus were detected. Importantly, a disease‐specific decline of relative abundance of Bifidobacterium was observed in AIH patients. Lack of Bifidobacterium was associated with failure to achieve remission of AIH ( P   〈  0.001). Of potential therapeutic implication, Bifidobacterium abundance correlated with average protein intake ( P   〈  0.001). Random forests classification between AIH and PBC on the microbiome signature yielded an area under receiver operating characteristic curve (AUC) of 0.787 in the training cohort, and an AUC of 0.849 in an external validation cohort. Conclusion Disease‐specific faecal microbial alterations were identified in patients with AIH. Intestinal dysbiosis in AIH was characterised by a decline of Bifidobacterium , which was associated with increased disease activity. These results point to the contribution of intestinal microbiota to AIH pathogenesis and to novel therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v51.12
    DOI: 10.1111/apt.15754
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 3
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    Pseudomonas aeruginosa populations in the cystic fibrosis lung lose susceptibility to newly applied β-lactams within 3 days
    Oxford University Press (OUP) ; 2019
    In:  Journal of Antimicrobial Chemotherapy Vol. 74, No. 10 ( 2019-10-01), p. 2916-2925
    Details
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 74, No. 10 ( 2019-10-01), p. 2916-2925
    Abstract: Chronic pulmonary infections by Pseudomonas aeruginosa require frequent intravenous antibiotic treatment in cystic fibrosis (CF) patients. Emergence of antimicrobial resistance is common in these patients, which to date has been investigated at long-term intervals only. Objectives To investigate under close to real-time conditions the dynamics of the response by P. aeruginosa to a single course of antibiotic therapy and the potentially associated rapid spread of antimicrobial resistance, as well as the impact on the airway microbiome. Methods We investigated a cohort of adult CF patients that were treated with a single course of antimicrobial combination therapy. Using daily sampling during treatment, we quantified the expression of resistance by P. aeruginosa (median of six isolates per daily sample, 347 isolates in total), measured bacterial load by P. aeruginosa-specific quantitative PCR and characterized the airway microbiome with a 16S rRNA-based approach. WGS was performed to reconstruct intrapatient strain phylogenies. Results In two patients, we found rapid and large increases in resistance to meropenem and ceftazidime. Phylogenetic reconstruction of strain relationships revealed that resistance shifts are probably due to de novo evolution and/or the selection of resistant subpopulations. We observed high interindividual variation in the reduction of bacterial load, microbiome composition and antibiotic resistance. Conclusions We show that CF-associated P. aeruginosa populations can quickly respond to antibiotic therapy and that responses are patient specific. Thus, resistance evolution can be a direct consequence of treatment, and drug efficacy can be lost much faster than usually assumed. The consideration of these patient-specific rapid resistance shifts can help to improve treatment of CF-associated infections, for example by deeper sampling of bacteria for diagnostics, repeated monitoring of pathogen susceptibility and switching between drugs.
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    URL: Article
    DOI: 10.1093/jac/dkz297
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
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  • 4
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    Alterations of the bile microbiome in primary sclerosing cholangitis
    BMJ ; 2020
    In:  Gut Vol. 69, No. 4 ( 2020-04), p. 665-672
    Details
    In: Gut, BMJ, Vol. 69, No. 4 ( 2020-04), p. 665-672
    Abstract: Patients with primary sclerosing cholangitis (PSC) display an altered colonic microbiome compared with healthy controls. However, little is known on the bile duct microbiome and its interplay with bile acid metabolism in PSC. Methods Patients with PSC (n=43) and controls without sclerosing cholangitis (n=22) requiring endoscopic retrograde cholangiography were included prospectively. Leading indications in controls were sporadic choledocholithiasis and papillary adenoma. A total of 260 biospecimens were collected from the oral cavity, duodenal fluid and mucosa and ductal bile. Microbiomes of the upper alimentary tract and ductal bile were profiled by sequencing the 16S-rRNA-encoding gene (V1–V2). Bile fluid bile acid composition was measured by high-performance liquid chromatography mass spectrometry and validated in an external cohort (n=20). Results The bile fluid harboured a diverse microbiome that was distinct from the oral cavity, the duodenal fluid and duodenal mucosa communities. The upper alimentary tract microbiome differed between PSC patients and controls. However, the strongest differences between PSC patients and controls were observed in the ductal bile fluid, including reduced biodiversity (Shannon entropy, p=0.0127) and increase of pathogen Enterococcus faecalis (FDR=4.18×10 −5 ) in PSC. Enterococcus abundance in ductal bile was strongly correlated with concentration of the noxious secondary bile acid taurolithocholic acid (r=0.60, p=0.0021). Conclusion PSC is characterised by an altered microbiome of the upper alimentary tract and bile ducts. Biliary dysbiosis is linked with increased concentrations of the proinflammatory and potentially cancerogenic agent taurolithocholic acid.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2019-318416
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1492637-4
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  • 5
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    Gut mycobiome of primary sclerosing cholangitis patients is characterised by an increase of Trichocladium griseum and Candida species
    BMJ ; 2020
    In:  Gut Vol. 69, No. 10 ( 2020-10), p. 1890-1892
    Details
    In: Gut, BMJ, Vol. 69, No. 10 ( 2020-10), p. 1890-1892
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2019-320008
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1492637-4
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  • 6
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    Long-term instability of the intestinal microbiome is associated with metabolic liver disease, low microbiota diversity, diabetes mellitus and impaired exocrine pancreatic function
    BMJ ; 2021
    In:  Gut Vol. 70, No. 3 ( 2021-03), p. 522-530
    Details
    In: Gut, BMJ, Vol. 70, No. 3 ( 2021-03), p. 522-530
    Abstract: The intestinal microbiome affects the prevalence and pathophysiology of a variety of diseases ranging from inflammation to cancer. A reduced taxonomic or functional diversity of the microbiome was often observed in association with poorer health outcomes or disease in general. Conversely, factors or manifest diseases that determine the long-term stability or instability of the microbiome are largely unknown. We aimed to identify disease-relevant phenotypes associated with faecal microbiota (in-)stability. Design A total of 2564 paired faecal samples from 1282 participants of the population-based Study of Health in Pomerania (SHIP) were collected at a 5-year (median) interval and microbiota profiles determined by 16S rRNA gene sequencing. The changes in faecal microbiota over time were associated with highly standardised and comprehensive phenotypic data to determine factors related to microbiota (in-)stability. Results The overall microbiome landscape remained remarkably stable over time. The greatest microbiome instability was associated with factors contributing to metabolic syndrome such as fatty liver disease and diabetes mellitus. These, in turn, were associated with an increase in facultative pathogens such as Enterobacteriaceae or Escherichia/Shigella . Greatest stability of the microbiome was determined by higher initial alpha diversity, female sex, high household income and preserved exocrine pancreatic function. Participants who newly developed fatty liver disease or diabetes during the 5-year follow-up already displayed significant microbiota changes at study entry when the diseases were absent. Conclusion This study identifies distinct components of metabolic liver disease to be associated with instability of the intestinal microbiome, increased abundance of facultative pathogens and thus greater susceptibility toward dysbiosis-associated diseases.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2020-322753
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1492637-4
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  • 7
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    Differences in the microbiota of native and non-indigenous gelatinous zooplankton organisms in a low saline environment
    Elsevier BV ; 2020
    In:  Science of The Total Environment Vol. 734 ( 2020-09), p. 139471-
    Details
    In: Science of The Total Environment, Elsevier BV, Vol. 734 ( 2020-09), p. 139471-
    Type of Medium: Online Resource
    ISSN: 0048-9697
    URL: Article
    DOI: 10.1016/j.scitotenv.2020.139471
    RVK:
    AR 10100
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1498726-0
    detail.hit.zdb_id: 121506-1
    SSG: 12
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  • 8
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    Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-04-12)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-04-12)
    Abstract: The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-31840-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 9
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    Heart failure is associated with depletion of core intestinal microbiota
    Wiley ; 2017
    In:  ESC Heart Failure Vol. 4, No. 3 ( 2017-08), p. 282-290
    Details
    In: ESC Heart Failure, Wiley, Vol. 4, No. 3 ( 2017-08), p. 282-290
    Abstract: In spite of current medical treatment approaches, mortality of chronic heart failure (HF) remains high and novel treatment modalities are thus urgently needed. A recent theory proposes a possible impact of the intestinal microbiome on the incidence and clinical course of heart failure. This study sought to systematically investigate, if there are specific changes of the intestinal microbiome in heart failure patients. Methods and results The intestinal microbiome of 20 patients with heart failure with reduced ejection fraction due to ischemic or dilated cardiomyopathy was investigated by applying high‐throughput sequencing of the bacterial 16S rRNA gene. Microbial profiles were compared to those of matched controls in which heart failure was ruled out by clinical assessment and NT‐proBNP serum levels ( n  = 20) . According to the Shannon diversity index (which measures the intra‐individual alpha‐diversity) based on the distribution of operational taxonomic units (OTUs), HF cases showed a nominally significantly lower diversity index compared to controls ( P nom.  = 0.01), and testing for genera abundance showed a tendency towards a decreased alpha diversity of HF patients. Beta‐diversity measures (inter‐individual diversity) revealed a highly significant separation of HF cases and controls, (e.g. P weighted UniFracv  = 0.004). Assessing the individual abundance of core measurable microbiota (CMM), a significant decrease of Coriobacteriaceae , Erysipelotrichaceae and Ruminococcaceae was observed on the family level. In line with that, Blautia , Collinsella , uncl. Erysipelotrichaceae and uncl. Ruminococcaceae showed a significant decrease in HF cases compared to controls on the genus level. Conclusions Heart failure patients showed a significantly decreased diversity of the intestinal microbiome as well as a downregulation of key intestinal bacterial groups. Our data point to an altered intestinal microbiome as a potential player in the pathogenesis and progression of heart failure.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    URL: Article
    DOI: 10.1002/ehf2.v4.3
    DOI: 10.1002/ehf2.12155
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2814355-3
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  • 10
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    Data_Sheet_1.xlsx
    Frontiers Media SA ; 2023
    In:  Frontiers in Medicine Vol. 10 ( 2023-7-31)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 10 ( 2023-7-31)
    Abstract: Inflammatory Bowel Disease (IBD) affects approximately 0.3% of the global population, with incidence rates rising dramatically worldwide. Emerging evidence points to an interplay between exposome factors such as diet and gut microbiota, host genetics, and the immune system as crucial elements in IBD development. ATP-binding cassette (ABC) transporters, including human p-glycoprotein encoded by the Abcb1 gene, influence intestinal inflammation, and their expression may interact with environmental factors such as diet and gut microbes. Our study aimed to examine the impact of protein sources on a genetic colitis mouse model. Methods Abcb1a-deficient colitis mice were fed either casein or red meat-supplemented diets to investigate potential colitis-aggravating components in red meat and their effects on host-microbiota interactions. We conducted deep label free quantitative proteomic inflammation profiling of gastrointestinal tissue (colon, ileum) and urine, and determined the overall microbiome in feces using 16S rRNA gene sequencing. Microbiota shifts by diet and protein transporter impairment were addressed by multivariate statistical analysis. Colon and systemic gut inflammation were validated through histology and immune assays, respectively. Results A quantitative discovery based proteomic analysis of intestinal tissue and urine revealed associations between ileum and urine proteomes in relation to Abcb1a deficiency. The absence of Abcb1a efflux pump function and diet-induced intestinal inflammation impacted multiple systemic immune processes, including extensive neutrophil extracellular trap (NET) components observed in relation to neutrophil degranulation throughout the gastrointestinal tract. The colitis model’s microbiome differed significantly from that of wild-type mice, indicating the substantial influence of efflux transporter deficiency on microbiota. Conclusion The proteomic and microbiota analyzes of a well-established murine model enabled the correlation of gastrointestinal interactions not readily identifiable in human cohorts. Insights into dysregulated biological pathways in this disease model might offer translational biomarkers based on NETs and improved understanding of IBD pathogenesis in human patients. Our findings demonstrate that drug transporter deficiency induces substantial changes in the microbiota, leading to increased levels of IBD-associated strains and resulting in intestinal inflammation. GRAPHICAL ABSTRACT
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2023.1200317
    DOI: 10.3389/fmed.2023.1200317.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2775999-4
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