Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction
Tzu-Wen L. Cross,
Abigayle M. R. Simpson,
Ching-Yen Lin,
Natasha M. Hottmann,
Aadra P. Bhatt,
Samuel J. Pellock,
Erik R. Nelson,
Brett R. Loman,
Matthew A. Wallig,
Eugenio I. Vivas,
Jan Suchodolski,
Matthew R. Redinbo,
Federico E. Rey,
Kelly S. Swanson
Affiliations
Tzu-Wen L. Cross
Department of Nutrition Science, Purdue University, West Lafayette, IN, USA
Abigayle M. R. Simpson
Department of Nutrition Science, Purdue University, West Lafayette, IN, USA
Ching-Yen Lin
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
Natasha M. Hottmann
Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
Aadra P. Bhatt
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
Samuel J. Pellock
Departments of Biochemistry & Biophysics, Microbiology & Immunology, and The Integrated Program for Biological and Genome Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Erik R. Nelson
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
Brett R. Loman
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
Matthew A. Wallig
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
Eugenio I. Vivas
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA
Jan Suchodolski
Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
Matthew R. Redinbo
Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA
Federico E. Rey
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA
Kelly S. Swanson
Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA
ABSTRACTWomen are at significantly greater risk of metabolic dysfunction after menopause, which subsequently leads to numerous chronic illnesses. The gut microbiome is associated with obesity and metabolic dysfunction, but its interaction with female sex hormone status and the resulting impact on host metabolism remains unclear. Herein, we characterized inflammatory and metabolic phenotypes as well as the gut microbiome associated with ovariectomy and high-fat diet feeding, compared to gonadal intact and low-fat diet controls. We then performed fecal microbiota transplantation (FMT) using gnotobiotic mice to identify the impact of ovariectomy-associated gut microbiome on inflammatory and metabolic outcomes. We demonstrated that ovariectomy led to greater gastrointestinal permeability and inflammation of the gut and metabolic organs, and that a high-fat diet exacerbated these phenotypes. Ovariectomy also led to alteration of the gut microbiome, including greater fecal β-glucuronidase activity. However, differential changes in the gut microbiome only occurred when fed a low-fat diet, not the high-fat diet. Gnotobiotic mice that received the gut microbiome from ovariectomized mice fed the low-fat diet had greater weight gain and hepatic gene expression related to metabolic dysfunction and inflammation than those that received intact sham control-associated microbiome. These results indicate that the gut microbiome responds to alterations in female sex hormone status and contributes to metabolic dysfunction. Identifying and developing gut microbiome-targeted modulators to regulate sex hormones may be useful therapeutically in remediating menopause-related diseases.
