Biology subjects

Yunusbaeva, M.

Publications and source records attributed to Yunusbaeva, M..

3 recordsLinked to original sources

bioRxiv2026

Genomic insights into the human gut commensal Megasphaera elsdenii: Relatedness and metabolic potential compared to animal isolates

Megasphaera elsdenii is best known as a prominent lactate consumer within the rumen microbial community in livestock, and its metabolic properties are relatively well studied. In humans, it can be isolated from healthy donors feces and, more often, from patients feces with diverse inflammatory conditions. Genetic diversity of this species is poorly understood, and it is currently unclear whether human and animal gut isolates are genetically related and perform the same metabolic function. In this study, we compared 86 M. elsdenii genomes from human feces (as a proxy for the human gut) to those of animal gut isolates. Phylogenetic analysis revealed that human and animal gut lineages intermingle within a single, genetically homogeneous branch, lacking any host-specific clustering. Human gut lineages shared most of their genes and biochemical pathways with those of swine and cattle gut isolates, despite differences in their digestive tracts. Neither unsupervised nor supervised approaches identified any notable differences in encoded pathways between different host-specific gut lineages. Genome-scale metabolic modeling suggests that human and animal gut lineages likely share identical carbon and energy source requirements. Moreover, the requirements for lactate and acetate were conserved across all studied samples, regardless of the host. Finally, we found no virulence genes, and lactate utilization remains a plausible explanation for M. elsdenii accumulation in the host intestine. IMPORTANCEMegasphaera elsdenii is considered a commensal in the human gut and animal rumen. However, M. elsdenii tends to be more abundant in patients feces with diverse inflammatory conditions. As we know little about the strain diversity and biology of human gut lineages, comparisons with better-studied animal isolates can be informative. In this study, we compared human gut M. elsdenii genomes to those from better-studied isolates from ruminant and non-ruminant animal hosts. Human gut samples associated with patients and healthy donors were genetically very similar to gut isolates from animals and may have shared a common origin. We found that human and animal gut lineages have a similar genomic makeup and metabolic potential, and that neither group harbors virulence genes. We hypothesize that M. elsdenii is a benign commensal that grows in response to lactate accumulation in the inflamed gut.

microbiology↗

bioRxiv2023

Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients

Gut microbiota link to host immunity motivated numerous studies of the gut microbiome in tuberculosis (TB) patients. However, these studies did not explore the metabolic capacity of the gut community, which is a key axis of impact on the hosts immunity. We used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the metabolic capacity and strain/species-level content of the gut microbiome. We show that the strong taxonomic divergence of the gut community in TB patients is explained by the systematic depletion of the commensal flora of the large intestine, Bacteroidetes, and an increase in Actinobacteria, Firmicutes, and Proteobacteria such as Streptococcaceae, Erysipelotrichaceae, Lachnospiraceae, and Enterobacteriaceae. The cumulative expansion of diverse disease-associated pathobionts in patients reached 1/4 of the total gut microbiota, suggesting a heavy toll on host immunity along with MTB infection. Reconstruction of metabolic pathways showed that the microbial community in patients shifted toward rapid growth using glycolysis and excess fermentation to produce acetate and lactate. Higher glucose availability in the intestine likely drives fermentation to lactate and growth, causing acidosis and endotoxemia. Excessive fermentation and lactic acidosis are likely characteristics of TB patients disturbed gut microbiomes. Since lactic acidosis strongly suppresses the normal gut flora, directly interferes with macrophage function, and is linked to mortality in TB patients, our findings highlight gut lactate acidosis as a novel research focus and a potential host-directed treatment target that can augment traditional TB treatment.

microbiology↗

bioRxiv2021

Prioritising Autoimmunity Risk Variants for Functional Analyses by Fine-Mapping Mutations Under Natural Selection

Pathogens imposed selective pressure on humans and shaped genetic variation in immunity genes. This can also be true for a fraction of causal variants implicated in chronic inflammatory disorders. Hence, locating adaptive mutations among candidate variants for these disorders can be a promising way to prioritize and decipher their functional response to microbial stimuli and contribution to pathogenesis. This idea has been discussed for decades, but challenges in locating adaptive SNPs hindered its application in practice. Our study addresses this issue and shows that a fraction of candidate variants for inflammatory conditions evolved under moderate and weak selection regimes (sweeps), and such variants are mappable. Using a novel powerful local-tree-based methodology, we show that 204 out of 593 risk loci for 21 autoimmune disorders contain at least one candidate SNP with strong evidence of selection. More importantly, in 28% of cases, these candidates for causal variants colocalize with SNPs under natural selection that we fine-mapped in this study. Causal SNPs under selection represent promising targets for functional experiments. Such experiments will help decipher molecular events triggered by infectious agents, a likely early event in autoimmunity. Finally, we show that a large fraction (60%) of candidate variants are either hitchhikers or linked with the selected mutation. Our findings, thus, support both hitchhiking and natural selection models, with the latter having important practical implications in medicine.

genetics↗