Antibiotic resistance gene sharing networks and the effect of dietary nutritional content on the canine and feline gut resistome

Abstract

Background: As one of the most densely populated microbial communities on Earth, the gut microbiota serves as an important reservoir of antibiotic resistance genes (ARGs), referred to as the gut resistome. Here, we investigated the association of dietary nutritional content with gut ARG diversity and composition, using publicly available shotgun metagenomic sequence data generated from canine and feline fecal samples. Also, based on network theory, we explored ARG-sharing patterns between gut bacterial genera by identifying the linkage structure between metagenomic assemblies and their functional genes obtained from the same data. Results: In both canine and feline gut microbiota, an increase in protein and a reduction in carbohydrate in the diet were associated with increased ARG diversity. ARG diversity of the canine gut microbiota also increased, but less strongly, after a reduction in protein and an increase in carbohydrate in the diet. The association between ARG and taxonomic composition suggests that diet-induced changes in the gut microbiota may be responsible for changes in ARG composition, supporting the links between protein metabolism and antibiotic resistance in gut microbes. In the analysis of the ARG-sharing patterns, 22 ARGs were shared among 46 genera in the canine gut microbiota, and 11 ARGs among 28 genera in the feline gut microbiota. Of these ARGs, the tetracycline resistance gene tet(W) was shared among the largest number of genera, predominantly among Firmicutes genera. Bifidobacterium, a genus extensively used in the fermentation of dairy products and as probiotics, shared tet(W) with a wide variety of other genera. Finally, genera from the same phylum were more likely to share ARGs than with those from different phyla. Conclusions: Our findings show that dietary nutritional content, especially protein content, is associated with the gut resistome and suggest future research to explore the impact of dietary intervention on the development of antibiotic resistance in clinically-relevant gut microbes. Our network analysis also reveals that the genetic composition of bacteria acts as an important barrier to the horizontal transfer of ARGs. By capturing the underlying gene-sharing relationships between different bacterial taxa from metagenomes, our network approach improves our understanding of horizontal gene transfer dynamics.