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 (i) influence of human gut bacteria microbiota on the gut resistome and (ii) the relationship between gut bacteria microbiota and E. coli resistome. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to systematically review published studies that characterised 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 bacterial gut microbiota and the resistome across different groups and the microbiota composition of the gut harbouring antibiotic-resistant E. coli were summarised. Lower diversity in the bacteria microbiota was associated with a concurrent increase in the abundance of the gut resistome. The gut microbiota of younger infants exhibited a lower diversity and was higher in the abundance of antibiotic-resistant genes (ARGs) compared to older infants and adults. A strong positive correlation was observed between the compositional relative abundance of Proteobacteria and ARGs abundance, mainly driven by members within the Enterobacteriaceae family, particularly E. coli. Employing a strategy that targets Enterobacteriaceae, with specific emphasis on E. coli, could be instrumental in controlling gut antibiotic resistance in humans. This study also revealed that human gut microbiome studies that investigate gut resistome using metagenomic sequencing approaches in apparently healthy individuals are at least uncommon.