High-fat and low-fiber diet elevates the gut resistome: a comparative metagenomic study

Antimicrobial resistance (AMR) is a global health challenge. The gut microbiome, a major reservoir for AMR, is influenced by dietary habits. However, the specific impact of dietary patterns on gut resistome remains poorly understood. This study aimed to assess the effects of high-fat/low-fiber and high-fiber/low-fat diets on the development of AMR in the gut microbiome. The shift from a normal diet to a high-fat/low-fiber or a high-fiber/low-fat diet in mice resulted in corresponding increases and decreases in the relative abundance of the resistome (0.14 to 0.25, p < 0.001 vs. 0.14 to 0.09 p < 0.05), virulence genes (VGs) (0.56 to 0.91, p < 0.001 vs. 0.58 to 0.50, p < 0.05), and mobile genetic elements (MGEs) (0.20 to 1.66, p < 0.001 vs. 0.22 to 0.13, p < 0.05), respectively. Network analyses identified bacteria such as Bacteroides, Parabacteroides, and Alistipes as hosts of ARGs and VGs, with changes in their abundance closely associated with shifts in ARG and VG levels. Mobile genetic elements such as Tn916, ISBf10, IS91, and intl1 were linked to these variations, including genes conferring resistance to vancomycin and capsule-related VGs. In humans, a similar trend was observed, with high-fat diets correlating with higher resistome levels, while high-fiber diets were associated with lower resistome levels compared to a normal diet group. ARGs were more prevalent in pathogenic genera such as Enterococcus spp., Klebsiella spp., Pseudomonas spp., and Staphylococcus spp. The high-fat/low-fiber diet increased the bacterial resistome and VG abundance compared to a high-fiber/low-fat diet. Therefore, adopting a high-fiber/low-fat diet may be an effective strategy to reduce the AMR burden in the human gut, providing a valuable insight for public health recommendations.