Major urinary protein (Mup) gene family deletion drives sex-specific alterations on the house mouse gut microbiota

Abstract

The gut microbiota is shaped by host metabolism. In house mice (Mus musculus), major urinary protein (MUP) pheromone production represents a considerable energy investment, particularly in sexually mature males. Deletion of the Mup gene family shifts mouse metabolism towards an anabolic state, marked by lipogenesis, lipid accumulation, and body mass increases. Given the metabolic implications of MUPs, they may also influence the gut microbiota. Here, we investigated the effect of deletion of the Mup gene family on the gut microbiota of sexually mature mice. Shotgun metagenomics revealed distinct taxonomic and functional profiles between wildtype and knockout males, but not females. Deletion of the Mup gene cluster significantly reduced diversity in microbial families and functions in male mice. Additionally, specific taxa of the Ruminococcaceae family, which is associated with gut health and reduced risk of developing metabolic syndrome, and several microbial functions, such as transporters involved in vitamin B5 acquisition, were significantly depleted in the microbiota of Mup-knockout males. Altogether these results show that major urinary proteins significantly affect the gut microbiota of house mouse in a sex-specific manner. ImportanceThe community of microorganisms that inhabit the gastrointestinal track of animals, known as the gut microbiota, can have profound effects on host phenotypes. The gut microbiota is in turn shaped by host genes, including those involved with host metabolism. In adult male house mice, expression of the major urinary protein (Mup) gene cluster represents a substantial energy investment, and deletion of Mup gene family leads to fat accumulation and weight gain in males. We show for the first time that deleting Mup genes also alters the gut microbiota of male, but not female, mice in terms of both taxonomic and functional composition. Male mice without Mup genes harbored fewer gut bacterial families and reduced abundances of several species, including bacteria previously shown to reduce obesity risk. Studying the impact of the Mup genes on the gut microbiota will help us understand how these genes influence host phenotype more broadly.