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Björk, J. R.

Publications and source records attributed to Björk, J. R..

3 recordsLinked to original sources

The gut microbiome across the cardiovascular risk spectrum

RationaleDespite significant progress in treatment strategies, cardiovascular disease remains a leading cause of death worldwide. Identifying new potential targets is crucial for enhancing preventive and therapeutic strategies. The gut microbiome has been associated with the development of coronary artery disease (CAD), however our understanding of the precise changes in the gut microbiome occurring during CAD development remains limited. ObjectiveTo investigate microbiome changes in participants without clinically manifest CAD with different cardiovascular risk levels and in patients with ST-elevation myocardial infarction (STEMI). Methods and ResultsIn this cross-sectional study we characterized the gut microbiome using metagenomics of 411 fecal samples from individuals with low (n=130), intermediate (n=130) and high (n=125) cardiovascular risk based on the Framingham score, and STEMI patients (n=26). We analyzed alpha and beta diversity of the gut microbiome and differential abundance of species and functional pathways among the different groups while accounting for confounders including medication and technical covariates. Abundances of Collinsella stercoris, Flavonifractor plautii and Ruthenibacterium lactatiformans showed a positive trend with cardiovascular risk, while Streptococcus thermophilus was negatively associated. Furthermore, in the differential abundance analysis we identified eight species and 49 predicted metabolic pathways that were differently abundant among the groups. These species included species linked to inflammation. Starch biosynthesis and phenolic compound degradation pathways were enriched in the gut microbiome of STEMI patients, while pathways associated with vitamin, lipid and amino-acid biosynthesis were depleted. ConclusionsWe identified four microbial species that demonstrated a gradual trend in their abundance from low risk individuals to those with STEMI, and species and pathways that were differently abundant in STEMI patients compared to groups without clinically manifest CAD. Further investigation is warranted to gain deeper understanding of their precise role in CAD progression and potential implications, with the ultimate goal of identifying novel therapeutic targets. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=142 HEIGHT=200 SRC="FIGDIR/small/546971v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@f7f0b1org.highwire.dtl.DTLVardef@1db0c8eorg.highwire.dtl.DTLVardef@154adeorg.highwire.dtl.DTLVardef@1e64c74_HPS_FORMAT_FIGEXP M_FIG C_FIG Created with BioRender.com

genomics↗

Universal gut microbial relationships in the gut microbiome of wild baboons

Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these relationships within hosts, and their generalizability across hosts, is essential to learn how microbial ecology scales up to affect microbiome assembly, dynamics, and host health. Here we gain insight into these patterns by inferring thousands of correlations in bacterial abundance between pairs of gut microbiome taxa from extensive time series data (5,534 microbiome profiles from 56 wild baboon hosts over a 13-year period). We model these time series using a statistically robust, multinomial logistic-normal modeling framework and test the degree to which bacterial abundance correlations are consistent across hosts (i.e., "universal") or individualized to each host. We also compare these patterns to two publicly available human data sets. We find that baboon gut microbial relationships are largely universal: correlation patterns within each baboon host reflect a mixture of idiosyncratic and shared patterns, but the shared pattern dominates by almost 2-fold. Surprisingly, the strongest and most consistently correlated bacterial pairs across hosts were overwhelmingly positively correlated and typically belonged to the same family--a 3-fold enrichment compared to pairs drawn from the data set as a whole. The bias towards universal, positive bacterial correlations was also apparent in monthly samples from human infants, and bacterial families that had universal relationships in baboons also tended to be universal in human infants. Together, our results advance our understanding of the relationships that shape gut microbial ecosystems, with implications for microbiome personalization, community assembly and stability, and the feasibility of microbiome interventions to improve host health.

ecology↗

Mucosal host-microbe interactions associate with clinical phenotypes in inflammatory bowel disease

Dysregulation of gut mucosal host-microbe interactions is a central feature of inflammatory bowel disease (IBD). To study tissue-specific interactions, we performed transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 696 intestinal biopsies derived from 353 patients with IBD and controls. Analysis of transcript-bacteria interactions identified six distinct groups of inflammation-related pathways that were associated with intestinal microbiota, findings we could partially validate in an independent cohort. An increased abundance of Bifidobacterium was associated with higher expression of genes involved in fatty acid metabolism, while Bacteroides was associated with increased metallothionein signaling. In fibrostenotic Crohns disease, a transcriptional network dominated by immunoregulatory genes associated with Lachnoclostridium bacteria in non-stenotic tissue. In patients using TNF--antagonists, a transcriptional network dominated by fatty acid metabolism genes associated with Ruminococcaceae. Mucosal microbiota composition was associated with enrichment of specific intestinal cell types. Overall, we identify multiple host-microbe interactions that may guide microbiota-directed precision medicine.

microbiology↗