biostudies-literatureUnknown2(11)Li YThe gut microbiome is essential for human health. Mouse microbiota models, including gnotobiotic mice, are the most prominent tools to elucidate the functions of gut bacteria. Here, we propose a targeted-bacterium-depleted (TBD) model using lytic bacteriophage to selectively deplete gut bacterium of healthy or otherwise defined mice. These phage-treated animals should have a near-complete spectrum of gut bacteria except for the depleted bacterium. To prove the concept, we employed <i>Escherichia coli</i>-specific phage T7 to repress <i>E. coli</i> in the healthy mice. Our results showed that the <i>E. coli-</i>depleted mice exhibited bravery-like behaviors, correlated to the presence of <i>E. coli</i> rather than the equilibrium among gut bacteria. Thus, we demonstrate that the TBD model is a powerful tool to elucidate the function of a specific bacterial species within a near-intact gut microbiota environment and complements gnotobiotic mice models.Cell reports methods100324https://www.ebi.ac.uk/biostudies/studies/S-EPMC9701607biostudies-literatureBacteriophages allow selective depletion of gut bacteria to produce a targeted-bacterium-depleted mouse model.PMC9701607Pan SHu ZZhu FMa XWang HYu JLiu XLi YYang ZLi TLiu BWang YWang ZBarritt JDfalseBacteriophages allow selective depletion of gut bacteria to produce a targeted-bacterium-depleted mouse model.The gut microbiome is essential for human health. Mouse microbiota models, including gnotobiotic mice, are the most prominent tools to elucidate the functions of gut bacteria. Here, we propose a targeted-bacterium-depleted (TBD) model using lytic bacteriophage to selectively deplete gut bacterium of healthy or otherwise defined mice. These phage-treated animals should have a near-complete spectrum of gut bacteria except for the depleted bacterium. To prove the concept, we employed <i>Escherichia coli</i>-specific phage T7 to repress <i>E. coli</i> in the healthy mice. Our results showed that the <i>E. coli-</i>depleted mice exhibited bravery-like behaviors, correlated to the presence of <i>E. coli</i> rather than the equilibrium among gut bacteria. Thus, we demonstrate that the TBD model is a powerful tool to elucidate the function of a specific bacterial species within a near-intact gut microbiota environment and complements gnotobiotic mice models.2022-01-01T00:00:00Z2022 Nov2025-04-21T14:28:18.951Z2025-04-21T14:28:18.951ZS-EPMC97016073645287210.1016/j.crmeth.2022.100324