Biology subjects

Utkina, I.

Publications and source records attributed to Utkina, I..

4 recordsLinked to original sources

bioRxiv2026

The gut microbiome of infants with hypoplastic left heart syndrome is enriched in pathobionts and exhibits altered responses to nutritional intervention

Congenital heart disease (CHD) can expose infants to chronic cyanosis, altered intestinal perfusion, and prolonged hospitalization. Altered gut microbiota has been linked to inflammation and gut barrier dysfunction in CHD cohorts, but few studies have examined whether cardiac severity and oxygenation shape microbial function, or whether this can be leveraged nutritionally, particularly for hypoplastic left heart syndrome (HLHS), the most hemodynamically severe common CHD lesion. We performed shotgun metagenomics on stool from 28 infants spanning the CHD severity spectrum, including HLHS (n=7), ventricular septal defect (n=8), tetralogy of Fallot (n=9), atrioventricular septal defect (n=2), and other lesions (n=2). We reconstructed 609 metagenome-assembled genomes, used for taxonomic and functional profiling, differential abundance testing, and oxygenation-associated modeling. Cardiac disease group was the strongest driver of taxonomic composition, with enrichment of the opportunistic Klebsiella specific to HLHS over contributions of feeding modality, birth type, or baseline oxygen saturation alone. HLHS communities showed a dual functional signature: depletion of core biosynthetic pathways, including aminoacyl-tRNA and peptidoglycan biosynthesis, alongside expansion of Enterobacteriaceae-driven aromatic amino acid catabolism and ABC transporters; this dual signature varied continuously with oxygenation. We then built infant-specific community metabolic models curated for human milk oligosaccharide metabolism and simulated a panel of feeding regimens. Individual microbiome identity, rather than diet, was the dominant determinant of predicted short-chain fatty acid (SCFA) production. In silico screening of dietary supplements identified threonine, methionine, and mucin-derived sugars as the strongest candidates for enhancing SCFA output, concentrated largely in formula-fed communities. These findings describe a coordinated shift in gut microbial function linked to CHD types and oxygenation, and provide a hypothesis-generating framework for microbiome-informed nutritional interventions in infants with severe CHD.

bioinformatics↗

bioRxiv2026

Multi-compartment spatiotemporal metabolic modeling of the chicken gut guides dietary intervention design

Understanding the interactions between diet and the gut microbiome is critical for identifying dietary interventions that support gut health. This is of particular importance for poultry where the elimination of antibiotic growth promoters has resulted in an alarming rise in enteric infections with significant economic consequences. While the application of computational models capable of dissecting the metabolic interactions supporting gut communities has shown promise, they remain limited, largely ignoring the physiological and geographical considerations of the poultry gastrointestinal tract. To address these limitations, we developed the first multi-compartment, spatiotemporally-resolved metabolic model of the chicken gastrointestinal tract. Our six-compartment framework integrates avian-specific physiological features including bidirectional flow, feeding-fasting cycles, and compartment-specific environmental parameters. The model captured distinct metabolic specialization along the gut, with upper compartments enriched for biosynthetic pathways and lower compartments specialized for fermentation. In silico screening of 34 dietary supplements revealed context-dependent metabolic responses and predicted cellulose, starch, and L-threonine as robust enhancers of short-chain fatty acid production. A controlled feeding trial validated key predictions, particularly for butyrate, with prediction accuracy further improved through integration of trial-specific microbial community data. Our findings demonstrate that community composition is a major driver of metabolic outcomes and underscore the need for context-specific modeling. Our framework provides a mechanistic platform for rational dietary intervention design and is broadly adaptable to other animal or human gastrointestinal systems.

bioinformatics↗

bioRxiv2024

Metabolic modeling of microbial communities in the chicken ceca reveals a landscape of competition and co-operation

With their ability to degrade dietary fibers to liberate otherwise unavailable substrates, members of the Bacteroidales exert a substantial influence on the microbiome of the lower intestine. Currently our knowledge of how this influence translates to the metabolic interactions that support community structure is limited. Here we applied constraints-based modeling to chicken cecal communities to investigate metabolic interactions in the presence and absence of Bacteroides. From metagenomic datasets previously generated from 33 chicken ceca, we constructed 237 metagenome-assembled genomes. Metabolic modeling of communities built from these genomes generated profiles of short chain fatty acids largely consistent with experimental assays and confirmed the role of B. fragilis as a metabolic hub, central to the production of metabolites consumed by other taxa. In its absence, communities undergo significant functional reconfiguration, with metabolic roles typically fulfilled by B. fragilis assumed by multiple taxa. Beyond B. fragilis, we found Escherichia coli and Lactobacillus crispatus also mediate influential metabolic roles that vary in the presence or absence of B. fragilis. Compensatory adaptations adopted by the microbiome in the absence of B. fragilis resulted in metabolic profiles previously associated with inflammatory bowel disease in humans, including energy deficiency, increased lactate production and altered amino acid metabolism. This work demonstrates the potential of chicken cecal microbiomes to investigate the complex metabolic interactions and key contributions that drive community dynamics.

systems biology↗

bioRxiv2021

A new platform for high-throughput therapy testing on iPSC-derived, immature airway from Cystic Fibrosis Patients

Induced pluripotent, stem cell (iPSC)-derived models of airway tissue have successfully modeled the primary defect in regulated chloride conductance caused by the major Cystic Fibrosis causing mutation, F508del. However, it remains unclear if iPSC-derived airway cultures can be used in high-throughput therapy development for F508del and rarer mutations. There is an urgent need for airway tissue models that reflect the variability of patient-specific responses and are scalable for therapy development. In the current work, we describe a robust, high-throughput fluorescence assay of mutant CFTR function in iPSCs differentiated to immature airway epithelium. This assay measures reproducible functional responses to modulators targeting either the major CF mutant F508del or the nonsense mutant: W1282X-CFTR. We show that the ranking of patient-specific responses to interventions in this stem-cell based model recapitulates the ranking observed in primary nasal epithelial cultures obtained from the same individuals. In summary, these proof-of-concept studies show that this novel platform has the potential to support therapy development and precision medicine for Cystic Fibrosis patients. One Sentence SummaryWe describe a fluorescence-based platform that enables high-throughput Cystic Fibrosis therapy testing using iPSCs differentiated to immature lung.

genomics↗