Parajuli, A. | bioRxiv Science

bioRxiv2024

Longitudinal blood microsampling and proteome monitoring facilitate timely intervention in experimental type 1 diabetes

Symptoms of immune-mediated diseases (IMIDs) typically appear after irreversible tissue damage, making early interventions based on pre-symptomatic indicators crucial. Current efforts to identify molecular markers of early disease lack the resolution, convenience and cost efficiency required to prevent irreversible tissue damage. Analyzing frequently self-collected samples, such as dried blood spots (DBS), could enable the earlier detection of diseases, identify disease-predictive markers and facilitate tailored interventions. To test this, we regularly microsampled a mouse model infected with a type 1-diabetes (T1D)-associated virus. This longitudinal DBS sample collection was analyzed for 92 circulating proteins, revealing transient molecular changes in virus-infected animals that would have been missed with less frequent sampling. Machine learning predicted infection status after day 2 post-infection with >90% accuracy, enabling well-timed treatment of virus-infected animals and diabetes prevention. Our study demonstrates the utility of frequent blood microsampling to monitor disease during the pre-symptomatic phase, allowing for timely interventions. TeaserFrequent blood microsampling detects early biomarkers, enabling timely intervention in immune-mediated diseases

systems biology↗

bioRxiv2024

Production, analysis, and safety assessment of a soil and plant-based natural material with microbiome- and immune-modulatory effects

Reduced contact with the microbiota from the natural environment has been suggested to contribute to the rising incidence of immune-mediated inflammatory disorders (IMIDs) in the western, highly urbanized societies. In line with this, we have previously shown that exposure to environmental microbiota in the form of a blend comprising of soil and plant-based material (biodiversity blend; BDB) enhances the diversity of human commensal microflora and promotes immunoregulation that may be associated with a reduced risk for IMIDs. To provide a framework for future preclinical studies and clinical trials, this study describes how the preparation of BDB was standardized, its microbial content and safety assessments. Multiple batches of BDB were manufactured and microbial composition analyzed using 16S rRNA gene sequencing. We observed a consistently high alpha diversity and relative abundance of bacteria normally found in soil and vegetation. We also found that inactivation of BDB by autoclaving effectively inactivates human and murine bacteria, viruses and parasites. Finally, we demonstrate that experimental mice prone to develop IMIDs (non-obese diabetic, NOD, mouse model) can be exposed to BDB without causing adverse effects on animal health and welfare. Our study lays the foundation for a safe, sustainable, and affordable way to mimic exposure to natural microbiota that has the potential to have enormous health- and socio-economic impacts.

microbiology↗