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Wacker, E. M.

Publications and source records attributed to Wacker, E. M..

4 recordsLinked to original sources

Industrialization drives convergent microbial and physiological shifts in the human metaorganism

Understanding how host lifestyle and industrialization shape the human gut microbiome and intestinal physiology requires multimodal analyses across diverse global host contexts. Here, we generate multivariate data from the Global Microbiome Conservancy cohort, including gut microbiome, IgA-sequencing, host genotyping, diet, lifestyle and fecal biomarker profiles, to investigate host-microbiome interactions across gradients of industrialization and geography. We show that industrialization is associated with homogenized microbial compositions, reduced microbial diversity, and lower community stability, independent of host confounders. We further show that industrialization is linked to elevated markers of gut stress, increased IgA secretion, and altered patterns of IgA-bacteria interactions. Finally, we show that microbiome-based disease predictors trained on industrialized populations lose accuracy in less industrialized cohorts, highlighting limited cross-population transferability. Together, our results suggest profound restructuring of host-microbiome interactions due to industrialized lifestyles, and emphasize the need for inclusive, globally representative data to improve translational microbiome applications across diverse human populations.

microbiology↗

Decoding the restriction of T cell receptors to human leukocyte antigen alleles using statistical learning

Conventional T cells recognize peptides presented by the human leukocyte antigen (HLA) proteins through their T cell receptors (TCRs). Given that thousands of HLA proteins have been discovered, each presenting thousands of different peptide antigens, decoding the cognate HLA protein of a TCR experimentally is a challenging task. To address this problem, we combined statistical learning methods with a unique dataset of paired T cell repertoires and HLA allele information for 6,794 individuals. This enabled us to discover 53,870 T cell receptor alpha (TRA) and 1,095,576 beta (TRB) clonotypes that were associated with 437 unique HLA alleles. The identified clonotypes were targeting prevalent infections, e.g. influenza, cytomegalovirus and Epstein-Barr virus. Utilizing these clonotypes, we developed statistical models that impute the carriership of common HLA alleles from the TRA- or TRB-repertoire. In conclusion, the identified allele-associated clonotypes encode the HLA fingerprints and the immune exposure history of individuals and populations.

immunology↗

Intestinal epithelial Atg16l1 influences pregnancy-induced fecal microbiota shifts in mice

Throughout gestation, the female body undergoes a series of transformations, including profound alterations in intestinal microbial communities. Changes gradually increase towards the end of pregnancy and comprise reduced -diversity of microbial communities and an increased propensity for energy harvest. Despite the importance of the intestinal microbiota for the pathophysiology of inflammatory bowel diseases, very little is known about the relationship between these microbiota shifts and pregnancy-associated complications of the disease. Here, we explored the longitudinal dynamics of gut microbiota composition and functional potential during pregnancy and after lactation in Atg16l1{Delta}IECmice carrying an intestinal epithelial deletion of the Croh[n]s disease risk gene Atg16l1. Using 16S rRNA amplicon and shotgun metagenomic sequencing, we demonstrated divergent temporal shifts in microbial composition between Atg16l1 wildtype and Atg16l1{Delta}IECpregnant mice in trimester 3, which was validated in an independent experiment. Observed differences included microbial genera implicated in IBD such as Lachnospiraceae, Roseburia, Ruminococcus, and Turicibacter. Changes partially recovered after lactation. In addition, functional inference of metagenomic data suggest a reduced potential to biosynthesize mucosal protective polyamines and reduced capacity to metabolize acidic polysaccharides (ketogluconate metabolism). On the host side, we found that the immunological response of Atg16l1{Delta}IEC mice is characterized by higher colonic mRNA levels of TNFA, and CXCL1 in trimester 3 and a lower weight of offspring at birth. Understanding pregnancy-dependent microbiome changes in the context of IBD may constitute the first step in the identification of fecal microbial biomarkers and microbiota-directed therapies that could help improving precision care for managing pregnancies in IBD patients.

microbiology↗

MAGScoT - a fast, lightweight, and accurate bin-refinement software

We introduce MAGScoT, a fast, lightweight and accurate implementation for the reconstruction of highest-quality metagenome-assembled genomes (MAGs) from the output of multiple genome-binning softwares. MAGScoT outperforms popular bin-refinement solutions in terms of quality and quantity of MAGs as well as computation time and resource consumption. MAGScoT is available via GitHub (https://github.com/ikmb/MAGScoT) and as an easy-to-use Docker container (https://hub.docker.com/repository/docker/ikmb/magscot).

bioinformatics↗