Abstract
Caloric restriction is well-established as a robust intervention that may extend lifespan and improve metabolic health across species with effects that are increasingly attributed to both host metabolic remodeling and alterations in the gut microbiota. Recent studies suggest that restricting specific dietary components can replicate these benefits. While methionine and branched-chain amino acid restriction improve metabolism and modulate the gut microbiome, the effects of other nutrients remain unclear. Here, we explore the effects of methionine, tryptophan and niacin deprivation on host intestinal gene expression and gut microbiota using female murine models. Through transcriptomic analysis of the intestinal tissue, we found that transient dietary restriction of methionine, tryptophan, and niacin induced significant changes in intestinal gene expression, particularly in genes involved in oxidative phosphorylation and ATP production. Single-cell analysis revealed that dietary restriction of those nutrients led to an increase in intestinal immune cell populations. Gut microbiota profiling also revealed that transient deprivation of those nutrients resulted in changes in microbial composition, with an increased relative abundance of Lactobacillus species observed in some cases. Our findings highlight the potential of targeted nutrient restriction as a strategy to reprogram host-microbiome interactions.