Biology subjects

Jansen, D.

Publications and source records attributed to Jansen, D..

6 recordsLinked to original sources

bioRxiv2023

Hidradenitis suppurativa patients exhibit a distinctive and highly individualized skin virome

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by recurring painful skin lesions. Despite ongoing research, the exact cause underlying the initiation and progression of disease remains unknown. While prior research has linked the skin microbiota to HS pathology, the role of viruses has remained unexplored. To investigate the skin virota, metagenomic sequencing of viral particles was performed on 144 skin samples from 57 individuals (39 HS patients and 18 controls). It was found that the virome is not only linked to BMI, but also to the presence and severity of HS, marking a diverging viral profile in the progression of disease. Despite no differences in alpha-diversity, HS patients exhibited a significantly higher beta-diversity compared to healthy controls, indicating a more personalized virome with reduced viral sharing among patients. We identified distinct groups of commonly shared phages, referred to as the core phageome, associated with either healthy controls or patients. Healthy controls displayed a higher abundance of two core Caudoviricetes phages predicted to infect Corynebacterium and Staphylococcus, comprising normal skin commensals. In contrast, HS patients carried previously uncharacterized phages that were more prevalent in advanced stages of the disease, which likely infect Peptoniphilus and Finegoldia, known HS-associated pathogens. Interestingly, genes involved in superinfection exclusion and antibiotic resistance could be found in phage genomes of healthy controls and HS patients, respectively. In conclusion, we report the existence of distinct core phages that may have clinical relevance in HS pathology by influencing skin bacteria through mechanisms such as superinfection exclusion and antibiotic resistance.

microbiology↗

bioRxiv2023

A fast method to distinguish between fermentative and respiratory metabolisms in single yeast cells

Saccharomyces cerevisiae adapts its metabolism according to nutrient availability. Typically, it rapidly ferments glucose to ethanol, and then shifts to respiration when glucose becomes limited. However, our understanding of the regulation of metabolism is largely based on population averages, whereas nutrient transitions may cause heterogeneous responses at the individual cell level. Although protein expression can be followed at the single-cell level as a proxy for metabolic modes, direct assessment of the contribution of respiration or (respiro)fermentation to energy metabolism is lacking. Here we describe a method to quickly differentiate between fermentative and respiratory metabolisms in individual cells of budding yeast. The method explores the use of the fluorescent FRET-based biosensor yAT1.03 to measure cytosolic ATP, coupled with the respiratory inhibitor Antimycin A. For the method validation, we used cells under fermentative and respiratory regimes from batch and chemostat cultures. Upon Antimycin A addition, we observed a sharp decrease of the normalized FRET ratio for respiratory cells; respirofermentative cells showed no response. Next, we tracked the changes in metabolism during the diauxic shift of a glucose pre-grown batch culture. Following glucose exhaustion, the entire cell population experienced a progressive rise in intracellular ATP produced via respiration, suggesting a uniform and gradual increase in respiratory capacity as cells pick up growth in a medium with ethanol as the sole carbon source. Overall, the combination of yAT1.03 with Antimycin A is a robust tool to distinguish fermentative from respiratory yeast cells, offering a new single-cell opportunity to study yeast metabolism. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/546324v1_figs1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1db7087org.highwire.dtl.DTLVardef@1b8b839org.highwire.dtl.DTLVardef@46d641org.highwire.dtl.DTLVardef@9c4aac_HPS_FORMAT_FIGEXP M_FIG Identification of fermentative and respiratory metabolisms in yeast cells using an ATP sensor coupled with a respiration inhibitor. (a) yAT1.03 consists of a donor (tdTomato) and an acceptor (ymTq2{Delta}11) domain linked by a binding domain with affinity to ATP. When ATP binds to the binding domain, donor and acceptor come together and the Forster energy is transferred from the first to the second domain. When expressed in in vivo cells the sensor allows real time measurements of ATP changes. (b) Depending on the growth conditions, yeast cells expressing yAT1.03 show a distinct response after being pulsed with the respiratory inhibitor Antimycin A (AA). The drop in ATP levels in respiratory cells caused by AA results from the inhibition of the mitochondrial electron transport chain. (c) Distinct metabolic responses to an AA pulse pre-, during and post-diauxic shift reveal distinct metabolic phenotypes. C_FIG

systems biology↗

bioRxiv2022

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↗

bioRxiv2021

Synchrony and idiosyncrasy in the gut microbiome of wild primates

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments, and medications, but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here we leverage extensive gut microbial time series from wild baboons--hosts who experience little interindividual dietary and environmental heterogeneity--to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiome dynamics were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, likely because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each hosts personalized dynamics. Indeed, host-specific factors, especially host identity, explained 10 times the deviance in longitudinal microbial dynamics, compared to factors shared across hosts. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artifact of modern human environments, and that synchronizing forces in the gut microbiome (e.g., shared environments, diets, and microbial dispersal) are often not strong enough to overwhelm drivers of microbiome personalization, including host genetics, priority effects, horizontal gene transfer, and functional redundancy.

ecology↗

bioRxiv2021

Successional stages in infant gut microbiota maturation

BackgroundDisturbances in the primary colonization of the infant gut can result in life-long consequences and have been associated with a range of host conditions. Although early life factors have been shown to affect the infant gut microbiota development, our current understanding of the human gut colonization in early life remains limited. To gain more insights in the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (total number of samples, n=303). To evaluate gut microbiota maturation transition towards an adult configuration, we compared the microbiome composition of the infants to the Flemish Gut Flora Project population (n=1,106). ResultsWe observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, genus predominance was observed to shift from Escherichia over Bifidobacterium to Bacteroides. Both disease and antibiotic treatment were observed to be associated occasionally with gut microbiota maturation stage regression, a transient setback in microbiota maturation dynamics. Although the studied microbiota trajectories evolved to more adult-like constellations, microbiome community typing against the background of the Flemish Gut Flora Project (FGFP) cohort clustered all infant samples within the (in adults) potentially dysbiotic Bact2 enterotype. ConclusionWe confirmed similarities between infant gut microbial colonization and adult dysbiosis. A profound knowledge about the primary gut colonization process in infants might provide crucial insights into how the secondary colonization of a dysbiotic adult gut can be redirected.

microbiology↗

bioRxiv2020

At least seven distinct rotavirus genotype constellations in bats with evidence of reassortment and zoonotic transmissions

Bats host many viruses pathogenic to humans, and increasing evidence suggests that Rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America and Africa were PCR-positive for RVA and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, including evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite varying levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses. ImportanceThe increased research on bat coronaviruses after SARS-CoV and MERS-CoVallowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents shed light on the vast genetic diversity of rotaviruses and also hinted at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.

microbiology↗