Jung, B. K. | Search bioRxiv

bioRxiv2026

Gut microbiota within-host evolution enforces colonization resistance against enteric infection

Limited resource availability in the gut promotes competitive interactions between bacteria, which drive adaptive within-host evolution (1-3). While adaptive evolution of bacterial communities has been increasingly studied in the recent years (4-7), its functional implications for host physiology remain unknown. Here, we show that within-host evolution of the human commensal Enterococcus faecalis boosts colonization resistance to enteric Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. During gut colonization, E. faecalis evolves the ability to metabolize fructoselysine, an abundant Amadori rearrangement product generated by thermal food processing. The depletion of this diet-derived nutrient prevents S. Typhimurium colonization by restricting an essential resource. This protective mechanism was conserved across independent mouse colonies and arises via diverse evolutionary trajectories, including nucleotide polymorphisms, gene amplifications, and a horizontal gene transfer event. Additionally, analysis of E. faecalis isolates from human infants revealed that adaptation to fructoselysine availability occurs in a diet-dependent manner. Isolates from infants fed with fructoselysine-rich formula were able to utilize fructoselysine, whereas those from infants fed with fructoselysine-poor breast milk were not. Conclusively, our results identify an inherent microbiome-driven self-healing mechanism, wherein bacterial evolution restores colonization resistance against enteric pathogens through evolved nutrient depletion. Understanding these evolutionary dynamics will inform microbiome-targeted approaches to prevent and treat infectious diseases by harnessing adaptive bacterial metabolism.

microbiology↗

bioRxiv2024

Multi-omics analysis and genome-scale metabolic reconstruction of cattle Bos taurus for optimal production of cultured meat

With the growing urgency of addressing climate change, cultured meat has gained significant attention as a sustainable alternative to conventional meat production. Bos taurus, a key cattle species, is considered as a potential source of cultured meat. However, much remains to be understood about the biology of B. taurus muscle cells. In this study, bovine satellite cells (BSCs) derived from the semimembranosus muscle of Korean Hanwoo cattle were subjected to multi-omics profiling and genome-scale metabolic reconstruction. First, differential gene expression and gene set enrichment analyses, based on RNA-seq data, identified key pathways associated with muscle cell proliferation (e.g., Cell cycle and RNA polymerase) and differentiation (e.g., Cytoskeleton in muscle cells and Tryptophan metabolism). Next, using the human1 GEM as a template, we constructed the first B. taurus-specific genome-scale metabolic model (GEM), named BtaSBML2986, which comprises 2,986 genes, 13,278 reactions, and 8,652 metabolites. Muscle cells were cultured under six distinct conditions, and biomass predictions generated using BtaSBML2986 were validated against experimental growth rates. This integrated approach also provided insights into core pathways such as glycolysis and the TCA cycle. BtaSBML2986 represents a significant step forward in understanding B. taurus muscle metabolism and will serve as a valuable tool for advancing cultured meat research and optimizing culture processes.

systems biology↗