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

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 toward 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 a deletion of the Mup gene family on the gut microbiota of sexually mature mice. Shotgun metagenomics revealed distinct taxonomic and functional profiles between wild-type and knockout males but not females. Deletion of the Mup gene cluster significantly reduced diversity in microbial families and functions in male mice. Additionally, a species of Ruminococcaceae 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 MUPs significantly affect the gut microbiota of house mouse in a sex-specific manner.IMPORTANCEThe community of microorganisms that inhabits the gastrointestinal tract 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 the Mup gene family leads to fat accumulation and weight gain in males. We show that deleting Mup genes also alters the gut microbiota of male, but not female, mice in terms of both taxonomic and functional compositions. Male mice without Mup genes harbored fewer gut bacterial families and reduced abundance of a species of Ruminococcaceae, a family that has been previously shown to reduce obesity risk. Studying the impact of the Mup gene family on the gut microbiota has the potential to reveal the ways in which these genes affect host phenotypes.

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

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.

Home-site advantage for host species-specific gut microbiota.

Mammalian species harbor compositionally distinct gut microbial communities, but the mechanisms that maintain specificity of symbionts to host species remain unclear. Here, we show that natural selection within house mice (Mus musculus domesticus) drives deterministic assembly of the house-mouse gut microbiota from mixtures of native and non-native microbiotas. Competing microbiotas from wild-derived lines of house mice and other mouse species (Mus and Peromyscus spp.) within germ-free wild-type (WT) and Rag1-knockout (Rag1-/-) house mice revealed widespread fitness advantages for native gut bacteria. Native bacterial lineages significantly outcompeted non-native lineages in both WT and Rag1-/- mice, indicating home-site advantage for native microbiota independent of host adaptive immunity. However, a minority of native Bacteriodetes and Firmicutes favored by selection in WT hosts were not favored or disfavored in Rag1-/- hosts, indicating that Rag1 mediates fitness advantages of these strains. This study demonstrates home-site advantage for native gut bacteria, consistent with local adaptation of gut microbiota to their mammalian species.

Histology and design-based estimation of hepatocellularity and volumes of hepatocytes in control and ethynylestradiol exposed males of platyfish (Xiphophorus maculatus).

The liver hosts numerous vital functions, such as biotransformation and excretion of xenobiotics. Synthetic oestrogens influence liver structure and function, leading to adaptations or to dysfunctions/injury. They are often stated to induce increases in fish liver weight, but there is controversy regarding how: if by changes in hepatocyte size (hypertrophy) and/or number (hyperplasia). Using platyfish as the experimental model, our primary aim was to assess if/how hepatocytes reacted to a sub-acute oestrogenic exposure. A complementary aim was to generate fundamental structural data for the liver of that model organism. Adult males were injected intramuscularly with 17α-ethinylestradiol (EE2) (25 µg/g), every 72 h for two weeks. Control fish were given solvent only. Body and liver morphometry were registered, and hepatocytes examined through histology and stereology at light microscopy. Immunohistochemistry evaluated hepatocytic vitellogenin (VTG) content. Treated and control fish did not differ as to quantitative parameters. Nevertheless, exposed fish were sensitive to EE2. VTG tagging was positive in their hepatocytes and these tended to be more basophilic, though not fully oestrogenized. We hypothesise that the platyfish liver is not particularly sensitive to the disrupting action of EE2 because of its reproductive mode; with no production peaks of VTG and no huge changes in endogenous sex-steroids. The fish may have had no evolutionary pressure for hepatocytes to be particularly reactive to oestradiol (E2). In the end, this study offers the first unbiased estimation of the liver cellularity in the platyfish, as well of the hepatocytic volume, serving now as a baseline reference.