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Antibiotic resistance is a global health problem. The human gut microbiome is implicated in the dynamics of antibiotic resistance acquisition and transmission, with the gut microbiota thought to play a crucial role. This study aimed to determine the potential influence of the human gut bacteria microbiota on the gut resistome and the relationship between the gut microbiota and Escherichia coli resistome. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was used to systematically review studies that characterized the gut microbiota and resistome using metagenomic analysis and/or those that reported gut E. coli resistome in healthy individuals. Changes in the diversity and abundance of the bacterial gut microbiota and the resistome across different time points and participant groups were summarized. Additionally, using E. coli resistome as a proxy for the gut resistome, the microbiota composition of the gut harboring antibiotic-resistant E. coli was examined. The findings suggest that lower bacterial microbiota diversity is likely associated with an increased abundance of the overall gut resistome. Age-related differences were observed, with younger infants exhibiting lower microbiota diversity and higher antibiotic resistance gene (ARG) abundance compared to older infants and adults. Studies that reported positive correlations between the relative abundance of Proteobacteria and ARGs were mainly driven by members within the Enterobacteriaceae family, mainly E. coli. This study also reveals that human gut microbiome studies investigating the gut resistome using metagenomic sequencing approaches in healthy individuals are uncommon. [ABSTRACT FROM AUTHOR]