Biology subjects

Andreasson, A.

Publications and source records attributed to Andreasson, A..

4 recordsLinked to original sources

bioRxiv2020

Genetics of human gut microbiome composition

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 out of 410 genera were detected in more than 95% samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 31 loci affecting microbiome at a genome-wide significant (P<5x10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (GWAS signal P=1.28x10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95x10-10<P<5x10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome has causal effects in ulcerative colitis and rheumatoid arthritis.

genetics↗

bioRxiv2019

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals

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. 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 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.

systems biology↗

bioRxiv2019

Transcriptional analysis identifies novel biomarkers associated with successful ex-vivo perfusion of human donor lungs

Transplantation is an effective treatment for end-stage lung disease but donor organ shortage is a major problem. Ex-vivo lung perfusion (EVLP) of marginal organs enables functional assessment under normothermic conditions to facilitate clinical decision-making around utilisation, but the molecular processes occurring during EVLP, and how they differ between more or less viable lungs, remains to be determined. Here we used RNA sequencing to delineate changes in gene expression occurring in n=10 donor lungs undergoing EVLP, comparing lungs that were deemed transplantable (n=6) to those deemed unusable (n=4). We found that lungs deemed suitable for transplantation following EVLP had reduced induction of a number of innate immune pathways during EVLP, but a greater increase in genes involved in oxidative phosphorylation, a critical ATP-degenerating pathway. Furthermore, SCGB1A1, a gene encoding an anti-inflammatory secretoglobin CC10, and other club cell genes were significantly increased in transplantable lungs following perfusion, whilst CHIT-1 was decreased. Using a larger validation cohort (n=18), we confirmed that the ratio of CHIT1 and SCGB1A1 protein levels in lung perfusate have potential utility to distinguish transplantable and non-transplantable lungs (AUC 0.81). Together, our data identify novel biomarkers that may assist with pre-transplant lung assessment, as well as pathways that may amenable to therapeutic intervention during EVLP.\n\nSingle sentence summaryTranscriptional changes in lungs undergoing ex vivo normothermic perfusion identify chitinase1 and club cell genes as potential biomarkers to guide utilisation

physiology↗

bioRxiv2019

Isolates from colonic spirochaetosis in humans show high genomic divergence and carry potential pathogenic features but are not detected by 16S amplicon sequencing using standard primers for the human microbiota

Colonic spirochaetosis, diagnosed based on the striking appearance in histological sections, still has an obscure clinical relevance and only 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. In these individuals, 17 (2.3 %) had colonic spirochaetosis, which was associated with eosinophilic infiltration and a three-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 spirochaetosis we successfully isolated, cultured and performed whole genome sequencing of in total 17 isolates including the Brachyspira aalborgi type strain 513AT. Also, 16S analysis of the mucosa-associated microbiota was performed in the cases and non-spirochaetosis controls. This is the first report of whole genome analysis of clinical isolates from individuals with colonic spirochaetosis. We found one isolate to be of the species Brachyspira pilosicoli and all remaining isolates were of the species Brachyspira aalborgi. Besides displaying extensive genetic heterogeneity, the isolates harboured several mucin-degrading enzymes and other virulence-associated 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 fail to detect Brachyspira due to primer incompatibility. This failure to detect colonic spirochaetosis should be taken into consideration in project design and interpretation of gastrointestinal tract microbiota in population-based and clinical settings.

microbiology↗