Biology subjects

Schuppe-Koistinen, I.

Publications and source records attributed to Schuppe-Koistinen, I..

7 recordsLinked to original sources

bioRxiv2026

Klebsiella pneumoniae T6SS exacerbates gut inflammation promoting tumorigenesis.

Dysbiosis and bacterial pathobionts contribute to inflammation in IBD and CRC, yet the molecular drivers of this process remain unclear. We identify the Klebsiella pneumoniae type VI secretion system (T6SS) as a key promoter of intestinal inflammation and tumor progression. Metagenomic analyses revealed enrichment of T6SS encoding genes in the gut microbiota of IBD patients during inflammatory flares. In zebrafish and mouse models, K. pneumoniae T6SS activity exacerbated inflammation and promoted colorectal tumor growth. Mechanistically, T6SS firing enhanced the secretion of LPS via outer membrane vesicles (OMVs), driving NF-{kappa}B activation and interferon signalling in host cells. In vivo, T6SS-dependent inflammation was associated with the expansion of regulatory T-cell subsets and an immunosuppressive tumor microenvironment. These findings redefine the T6SS as a microbial determinant of host inflammation and cancer progression, highlighting T6SS inhibition as a potential therapeutic approach for IBD and CRC. HighlightsO_LIT6SS-encoding Enterobacteria are enriched in the gut microbiota of IBD patients C_LIO_LIKlebsiella pneumoniae T6SS exacerbates colitis in mice C_LIO_LIT6SS activity enhances outer membrane vesicle secretion and LPS release C_LIO_LIT6SS promotes colorectal tumorigenesis and immune dysregulation C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/715367v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1c99341org.highwire.dtl.DTLVardef@e2d0eborg.highwire.dtl.DTLVardef@1021387org.highwire.dtl.DTLVardef@1502c97_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Vaginal Microbiome and Inflammation Among Chinese Women.

Human papillomavirus (HPV) infection, cervical intraepithelial neoplasia (CIN), pelvic organ prolapse (POP), cervical polyps (CP), abnormal uterine bleeding (AUB), and vaginitis are common conditions encountered in gynecological practice. In this study, we collected vaginal secretions from patients diagnosed with these diseases (n = 310) and from healthy donors (n = 112) to analyze their vaginal microbiome using 16S rRNA sequencing and cytokine expression using a cytometric bead array (CBA). Our findings revealed that the vaginal microbiome in POP patients exhibited higher complexity compared to other groups. Regarding cytokine expression, levels of IL-1, IL-1{beta}, IL-6, IL-8, MCP-1, and MIG were significantly elevated in HPV and CIN patients. Analysis of microbial associations showed that Lactobacillus crispatus and Lactobacillus iners were significantly negatively correlated with IL-1 and IL-1{beta} expression. In contrast, non-Lactobacillus bacteria, including Bifidobacterium breve, Prevotella bivia, Gardnerella vaginalis, Sneathia amnii, Sneathia sanguinegens, Prevotella amnii, Escherichia coli, and Chlamydia trachomatis, were positively correlated with IL-1, IL-1{beta}, IL-6, IL-8, MCP-1, and MIG levels. Furthermore, Lactobacillus iners exhibited a significant negative effect in the HPV and CIN patient groups.

microbiology↗

bioRxiv2024

Profiling the intestinal microbiota, plasma bile acids and inflammation markers reveals novel associations in Crohn's disease and Ulcerative colitis.

Background and aimsOur study explores signatures for Crohns disease (CD) and Ulcerative Colitis (UC) reflecting the interplay between the intestinal microbiota, systemic inflammation, and plasma bile acid homeostasis. Methods1,257 individuals scheduled for colonoscopy were included and completed a comprehensive questionnaire. Individuals with IBD ( CD n=64 and UC n= 55), were age- and gender-matched to controls without findings during colonoscopy. Taxonomic profiles of the fecal microbiota and plasma profiles of inflammatory proteins and bile acids were used to build disease classifiers. Omics integration identified associations across datasets. ResultsB. hydrogenotrophica was associated with CD and C. eutactus, C. sp. CAG 167, B. cellulosilyticus, C. mitsuokai with controls. Ten inflammation markers were increased in CD, and eleven bile acids and derivatives were decreased in CD, while 7a-Hydroxy-3-oxo-4-cholestenoate (7-HOCA) and chenodeoxycholic acid (CDCA) were increased compared to controls. In UC, commensals such as F. prausnitzii and A. muciniphila were depleted. CCL11, IL-17A, and TNF were increased in UC and associated to gut microbial changes. Correlations between taxa and bile acids were all positive. ConclusionsFor both CD and UC, taxonomic differences were primarily characterized by a reduction in commensal gut microbes which exhibited positive correlations with secondary bile acids and negative correlations with inflammation markers, potentially reflecting protective mechanisms of these commensal microbes.

bioinformatics↗

bioRxiv2023

Defining Vaginal Community Dynamics: daily microbiome transitions, the role of menstruation, bacteriophages and bacterial genes

BackgroundThe composition of the vaginal microbiota during the menstrual cycle is dynamic, with some women remaining eu- or dysbiotic and others transitioning between these states. What defines these dynamics, and whether these differences are microbiome-intrinsic or mostly driven by the host is unknown. To address this, we characterized 49 healthy, young women by metagenomic sequencing of daily vaginal swabs during a menstrual cycle. We classified the dynamics of the vaginal microbiome and assessed the impact of host behavior as well as microbiome differences at the species, strain, gene and phage levels. ResultsBased on the daily shifts in community state types (CSTs) during a menstrual cycle the vaginal microbiome was classified into four Vaginal Community Dynamics (VCDs) and reported in a classification tool, named VALODY: constant eubiotic, constant dysbiotic, menses-related and unstable dysbiotic. The abundance of bacteria, phages, and bacterial gene content was compared between the four VCDs. Women with different VCDs showed significant differences in relative phage abundance and bacterial composition even when assigned to the same CST. Women with unstable VCDs had higher phage counts and were more likely dominated by L. iners. Their Gardnerella spp. strains were also more likely to harbour bacteriocin-coding genes. ConclusionsThe VCDs present a novel time series classification which highlights the complexity of varying degrees of vaginal dysbiosis. Knowing the differences in phage levels and the genomic strains present allows a deeper understanding of the initiation and maintenance of permanent dysbiosis. Applying the VCDs to further characterize the different types of microbiome dynamics qualifies the investigation of disease and enables comparisons at individual and population levels. Based on our data, to be able to classify a dysbiotic sample into the accurate VCD, clinicians would need two-three mid-cyclical samples and two samples during menses. In the future, it will be important to address whether transient VCDs pose a similar risk profile to persistent dysbiosis with similar clinical outcomes. This framework may aid interdisciplinary translational teams in deciphering the role of the vaginal microbiome in womens health and reproduction.

microbiology↗

bioRxiv2020

Optimal protocols for sequence-based characterization of the human vaginal microbiome

The vaginal microbiome has been connected to a wide range of health outcomes. This has led to a thriving research environment, but also to the use of conflicting methodologies to study its microbial composition. Here we systematically assess best practices for the sequencing-based characterization of the human vaginal microbiome. As far as 16S rRNA gene sequencing is concerned, the V1-V3 region has the best theoretical properties, but limitations of current sequencing technologies mean that the V3-V4 region performs equally well. Both of these approaches present very good agreement with qPCR quantification of key taxa, provided an appropriate bioinformatic pipeline is used. Shotgun metagenomic sequencing presents an interesting alternative to 16S amplification and sequencing, but it is not without its challenges. We have assessed different tools for the removal of host reads and the taxonomic annotation of metagenomic reads, including a new, easy-to-build and - use, reference database of vaginal taxa. This strategy performed as well as the best performing previously published strategies. Despite the many advantages of shotgun sequencing none of the shotgun approaches assessed here had as good agreement with the qPCR data as 16S rRNA gene sequencing. ImportanceThe vaginal microbiome has been connected to a wide range of health outcomes, from susceptibility to sexually transmitted infections to gynecological cancers and pregnancy outcomes. This has led to a thriving research environment, but also to conflicting available methodologies, including many studies that do not report their molecular biological and bioinformatic methods in sufficient detail for them to be considered reproducible. This can lead to conflicting messages and delay progress from descriptive to intervention studies. By systematically assessing best practices for the characterization of the human vaginal microbiome, this study will enable past studies to be assessed more critically and assist future studies in the selection of appropriate methods for their specific research questions.

molecular biology↗

bioRxiv2020

Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling

BackgroundPrecision medicine approaches aim to tackle diseases on an individual level through molecular profiling. Despite the growing knowledge about diseases and the reported diversity of molecular phenotypes, the descriptions of human health on an individual level have been far less elaborate. MethodsTo provide insights into the longitudinal protein signatures of well-being, we profiled blood plasma collected over one year from 101 clinically healthy individuals using multiplexed antibody assays. After applying an antibody validation scheme, we utilized > 700 protein profiles for in-depth analyses of the individuals short-term health trajectories. FindingsWe found signatures of circulating proteomes to be highly individual-specific. Considering technical and longitudinal variability, we observed both stable and fluctuating proteins in the circulation, as well as networks of proteins that covaried over time. For each participant, there were unique protein profiles and some of these could be explained by associations to genetic variants. InterpretationThis study demonstrates that there was noticeable diversity among clinically healthy subjects, and facets of individual-specific signatures emerged by monitoring the variability of the circulating proteomes over time. Longitudinal profiling of circulating proteomes has the potential to enable a more personal hence precise assessment of health states, and thereby provide a valuable component of precision medicine approaches. FundingThis work was supported by the Erling Persson Foundation for the KTH Centre for Precision Medicine and the Swedish Heart and Lung Foundation for the SCAPIS project. We also acknowledge the Knut and Alice Wallenberg Foundation for funding the Human Protein Atlas project, Science for Life Laboratory for Plasma Profiling Facility, and the Swedish Research Council (Grant no 2017-00641).

biochemistry↗

bioRxiv2018

A comprehensive automated pipeline for human microbiome sampling, 16S rRNA gene sequencing and bioinformatics processing

The advent of affordable high-throughput DNA sequencing has opened up a golden age of studies in the human microbiome. In order to understand the role of the human microbiota, standardized methods for large-scale, population-level studies are needed to avoid underpowered or poorly designed studies. The biggest bottlenecks to population-level microbiomics are sample collection, storage and DNA extraction. Here, we describe a flexible automated approach to process intestinal biopsies, fecal samples and vaginal swabs from sample collection to OTU table. We have evaluated storage conditions, DNA extraction methods, PCR strategies and bioinformatic pipelines for these three sample types, and present here a set of guidelines and best practices for each of these steps.

microbiology↗