Biology subjects

Bielecka, A.

Publications and source records attributed to Bielecka, A..

3 recordsLinked to original sources

bioRxiv2024

Comparative analysis of the treatment-naive microbiome across rheumatic diseases to predict MTX treatment response

The human gut microbiota is recognized as a modulator of inflammatory diseases and has been linked to interindividual differences in therapy responsiveness. However, the robustness of disease-specific microbiome signatures across closely related diseases is rarely compared. Here, we compared treatment-naive microbiota composition and functional potential across rheumatic diseases, including rheumatoid arthritis (RA) and spondyloarthritis subforms, to identify disease-specific biomarkers. While we failed to define robust disease-specific microbiota signatures, we identified microbial signatures linked to methotrexate (MTX) responsiveness for the two rheumatic diseases RA and psoriatic arthritis (PsA), for which MTX is the first-line treatment. Notably, the signatures were distinct, i.e., we could define a signature based on the relative abundance of microbial species for RA, yet the signature for PsA was based on the relative abundance of microbial pathways. Together this supports the previously recognized value of microbiota to predict treatment responses to MTX in RA and identifies distinct signatures predicting MTX responsiveness for PsA.

microbiology↗

bioRxiv2021

Versatile genetic toolbox for Prevotella copri enables studying polysaccharide utilization systems

Prevotella copri is a prevalent inhabitant of the human gut and has been associated with plant-rich diet consumption and diverse health states. The underlying genetic basis of these associations remains enigmatic due to the lack of genetic tools. Here, we developed a novel versatile genetic toolbox for rapid and efficient genetic insertion and allelic exchange applicable to P. copri strains from multiple clades. Enabled by the genetic platform, we systematically investigated the specificity of polysaccharide utilization loci (PULs), and identified four highly conserved PULs for utilizing arabinan, pectic galactan, arabinoxylan and inulin, respectively. Further genetic and functional analysis of arabinan utilization systems illustrate that P. copri has evolved two distinct types of arabinan-processing PULs (PULAra) and that the type-II PULAra is significantly enriched in individuals consuming a vegan diet compared to other diets. In summary, this genetic toolbox will enable functional genetic studies for P. copri in the future.

microbiology↗

bioRxiv2018

IgA-deficient humans exhibit gut microbiota dysbiosis despite production of compensatory IgM

Immunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) is the most common primary immunodeficiency in humans and is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and IgA or IgM coating of the gut microbiota in 15 sIgAd subjects and 15 matched controls. Although sIgAd subjects secreted a significant amount of IgM into the intestinal lumen, this was insufficient to fully compensate for the lack of secretory IgA. Indeed, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls, which was characterized by a trend towards decreased overall microbial diversity and significant shifts in the relative abundances of specific microbial taxa. While IgA targets a defined subset of the microbiota via high-level coating, compensatory IgM binds a broader subset of the microbiota in a less targeted manner. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community that promotes human health, enhances resistance to infection, and is resilient to perturbation.

immunology↗