Phages dominate the human gut virome and are known for their ability to prey on bacteria and shape microbiota. However, their response to diet has only been elucidated using small-scale studies. By integrating a massive meta-analysis of 6932 diet-associated metagenomes with a time-resolved mouse model of a high-fat diet and polysaccharide intake, the impact of diet on the gut virome and phage-bacterial interactions was systematically characterized. Diet types, particularly high-fat and polysaccharide-rich diets, exert the strongest shaping force on the gut virome, enhancing the crosstalk between phages and bacteria. High-fat diets promote changes in phage abundance across a broad taxonomic range, from 34.21% to 50.00%, drive phages of diet-associated bacteria toward a lytic lifestyle, and remarkably enrich auxiliary metabolic genes related to amino acid metabolism. Conversely, fucoidan reversed HFD-induced dysbiosis and enhanced phage-mediated horizontal gene transfer by 8.5-fold relative to the baseline. crAssphages and Parabacteroides phages may be important contributors, broadly supporting horizontal gene transfer and auxiliary metabolism or strengthening phage-host interactions in polysaccharide interventions, including fucoidan supplementation. These findings provide a comprehensive landscape of diet-driven cross-kingdom interactions and phage-mediated gene exchange in the gut, offering new insights into potential strategies for precise nutritional interventions targeting the intestinal microbiota.
Zhao et al. (Thu,) studied this question.