Biology subjects

Jebens, H.

Publications and source records attributed to Jebens, H..

3 recordsLinked to original sources

bioRxiv2025

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↗

bioRxiv2025

Convergent genomic responses of human gut bacteria to variations in industrialization

To what extent gut bacteria respond to the distinct ecological pressures imposed by human lifestyle remains unclear. Here, we investigate how genomic adaptation in gut bacteria differ between industrialized and non-industrialized human populations. We generated a broad collection of isolate genomes spanning diverse host geographies, lifestyles, species, and strains. We first found that compared to MAGs, paired isolate genomes recover more functional elements and signals of horizontal gene transfers (HGTs). Leveraging isolate genomes from multiple species, we find that strains from industrialized hosts experience an expansion of proteome size and harbor greater pangenome fluidity, driven by recent events of HGTs. Gene- and variant-level analyses reveal convergent patterns of lifestyle-specific adaptation in functions that are critical for ecological adaptation, such as stress response, cell envelope remodeling and central metabolism. Our results demonstrate that industrialization imprints evolutionary signatures on gut bacterial genomes, illuminating the effects of rapidly changing environments on human biology.

evolutionary biology↗

bioRxiv2025

Mapping adaptive immune responses toward fungal antigens in inflammatory bowel disease using T cell repertoire sequencing and phage-immunoprecipitation sequencing

Inflammatory bowel disease (IBD) is an idiopathic, immune-mediated chronic inflammatory disease of the gut with two primary clinical forms, Crohns disease (CD) and ulcerative colitis (UC). Several genetic susceptibility variants have been associated with IBD, such as ATG16L, NOD2, and several human leukocyte antigen (HLA) alleles, nonetheless, the actual disease causes remain unknown. Whereas previous findings have shown elevated responses toward fungal antigens in individuals with IBD, e.g., elevated anti-Saccharomyces cerevisiae antibody (ASCA) levels, an exhaustive mapping of immune responses toward fungal antigens remains incomplete. Thus, we analyzed the fungal mycobiome profiled using internal transcribed spacer 2 (ITS2)-sequencing simultaneously with the T cell repertoire of 637 individuals with IBD from the SPARC IBD cohort, which enabled us to identify 31 T cell clonotypes targeting several prevalent members of the gut mycobiome. Subsequently, we developed a novel phage-immunoprecipitation sequencing (PhIP-Seq) library covering 12,000 potential antigens from the proteome of S. cerevisiae and screened for antibody responses in 100 individuals with CD and 60 healthy controls with known ASCA status, enabling us to identify public and private antibody responses against several S. cerevisiae proteins. In conclusion, we corroborated previous findings showing elevated T cell responses against fungal antigens in individuals with IBD and identified multiple antigenic proteins from the proteome of S. cerevisiae that are targeted by the immune system of individuals with and without CD.

immunology↗