The microbiome protects against septic hyperinflammation and bacterial proliferation in a zebrafish model of blood infection with E.coli and mycobacteria

Here, we establish a gnotobiotic zebrafish larval model to investigate microbiome-dependent protection against systemic blood infection by E. coli bacteria, an important cause of early onset neonatal sepsis and nontuberculous mycobacteria to investigate the contribution of Toll-like receptor 2 (TLR2) in the defense responses.

Germ-free (GF) and conventionalized (CONVD) larvae derived from the same clutches were systemically infected with E. coli, revealing that microbiome colonization significantly reduces early mortality. RNA-seq revealed a conserved core immune activation program in both GF and CONVD larvae, but the absence of a microbiome was associated with a broader transcriptional response and stronger repression of metabolic pathways, suggesting that commensal microbes buffer infection-induced metabolic suppression.