Biology subjects

Djukovic, A.

Publications and source records attributed to Djukovic, A..

4 recordsLinked to original sources

bioRxiv2026

Resource-access breadth marks protective strains against toxigenic Clostridioides difficile

Antibiotic disruption of gut microbiota creates opportunities for toxigenic Clostridioides difficile. One strategy is to occupy this niche with a non-toxigenic or weakly virulent strain, but even strains that cause little disease may fail to compete during pathogen challenge. We screened 21 sequence type 1 (ST1) isolates for their ability to protect mice co-colonized with toxigenic VPI10463, separating disease potential from protection. Some strains, such as ST1-75, caused little disease and protected, whereas others, such as ST1-68, caused little disease but failed to protect. Metabolomics showed that ST1-75 depleted more proline than ST1-68, whereas another protective strain, ST1-6, had a different metabolic profile; both protective strains nevertheless responded to many substrates. Substrate-utilization profiling revealed that protection across the 21 isolates correlated with amino-acid overlap with VPI10463, but not overall nutrient overlap or shared genome-encoded protein families. Relative amino-acid access explained variation beyond mono-colonization disease potential, and a consumer-resource model showed how nutrient overlap together with additional resource access can support persistence during competition. Additional experiments support that ST1-mediated protection occurs even in the absence of mature B and T cells. These findings distinguish low disease potential from protection, link protection to strain competition, and identify relative resource access as an informative phenotype for prioritizing strains for biotherapeutic testing.

microbiology↗

bioRxiv2026

Gut Commensals Regulate the Intestinal Kynurenine Pathway

The kynurenine pathway (KP) of tryptophan metabolism shapes host immunity and is implicated in inflammatory, malignant, and neurodegenerative diseases. Although it is well known that inflammation influences KP activity, whether and how gut microbiota regulates KP in the intestine remains unclear. Here, we find that in allogeneic hematopoietic cell transplant patients, the kynurenine-to-tryptophan ratio tracks plasma neopterin, whereas intestinal levels do not, suggesting that local KP regulation is not explained by inflammation alone. In mice, targeted microbiota perturbation downregulates intestinal expression of indoleamine 2,3-dioxygenase 1 (IDO1), the rate-limiting enzyme of the KP, while microbiota restoration reversed this effect. Computational analyses associate Lachnospiraceae and Oscillospiraceae with colonic IDO1 in mice and inflammatory bowel disease cohorts. In vitro experiments support a mechanism whereby microbiota perturbation alters host absorption of the vitamin E isoform, {gamma}-tocotrienol, which impacts IDO1 expression. Our findings support that the gut microbiota controls colonic KP through micronutrient absorption.

microbiology↗

bioRxiv2022

Relative enrichment of oral bacteria in feces indicates loss of intestinal commensals with implications for host health

The increased relative abundance of oral bacteria detected in fecal samples has been associated with intestinal diseases and digestive disorders. This observation raises two competing hypotheses: either oral bacteria invade the gut bacterial population and expand in the intestine (the Expansion hypothesis), or oral bacteria transit through and their relative increase in feces marks a depletion of the gut bacterial population (the Marker hypothesis). To address this, we conducted a comprehensive analysis of quantitative microbiome data from mouse experiments and diverse patient cohorts. Our findings consistently support the Marker hypothesis as the primary explanation. We further establish a robust inverse correlation between the total fraction of oral bacteria and decreased total bacterial abundance in feces. This correlation underlies the associations between the oral bacterial fraction and multiple patient outcomes consistent with a depleted gut microbiota. By distinguishing between the two hypotheses, our study guides the interpretation of microbiome compositional data and their links with human health.

microbiology↗

bioRxiv2022

The TaxUMAP atlas: efficient display of large clinical microbiome data reveals ecological competition involved in protection against bacteremia

The microbiome is associated with health and disease, but causal effects are hard to quantify-- especially in humans where controlled experiments are nearly impossible. Akin to natural experiments, closely monitored patients offer an alternative to characterize microbiome effects. We present TaxUMAP, a taxonomically-informed visualization method to effectively display diverse microbiome states. TaxUMAP charts a microbiome atlas from 1,870 cancer patients as they progress through therapy-induced perturbations, and quantifies the microbiome contribution to patients risk for life-threatening bacteremia. We find that the lowest diversity states (gut dominations) that follow antibiotic treatments are stable, and that diverse communities harbor more diverse antimicrobial resistance genes than dominations. We reveal that certain Klebsiella species are associated with reduced risk for bacteremia, an effect driven by bacterial competition that we validate experimentally in vitro and in vivo. TaxUMAP effectively maps longitudinal microbiome data that can facilitate research into causal microbiome effects on human health. HIGHLIGHTSO_LITaxUMAP charts an atlas of patients microbiome states and their clinical context to reveal new causal effects. C_LIO_LIAntibiotics deplete the biodiversity and reduce the number of different antimicrobial resistance genes in the gut microbiome. C_LIO_LICertain Klebsiella species are associated with lower risk of bacteremia by other gut-borne pathogens. C_LIO_LIThese Klebsiella outcompete other gram-negative pathogens in vivo. C_LI

microbiology↗