AUTHOR=Hallowell Haley A. , Higgins Keah V. , Roberts Morgan , Johnson Robert M. , Bayne Jenna , Maxwell Herris Stevens , Brandebourg Terry , Hiltbold Schwartz Elizabeth 

TITLE=Longitudinal Analysis of the Intestinal Microbiota in the Obese Mangalica Pig Reveals Alterations in Bacteria and Bacteriophage Populations Associated With Changes in Body Composition and Diet

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.698657

DOI=10.3389/fcimb.2021.698657

ISSN=2235-2988

ABSTRACT=Due to its immunomodulatory potential, the intestinal microbiota has been implicated as a contributing factor in the development of the meta-inflammatory state that drives obesity-associated insulin resistance and type 2 diabetes. To better understand the links between obesity and gut microbiota composition, we validated and utilized a novel swine model of obesity, the Mangalica pig. In the first study, we characterized the metabolic phenotype and gut microbiota in lean and obese adult Mangalica pigs. Obese or lean groups were created by allowing either ad libitum (obese) or restricted (lean) access to a standard diet for 54 weeks. Mature obese pigs were significantly heavier  and exhibited 170% greater subcutaneous adipose tissue mass, with no differences in muscle mass compared to their lean counterparts. Obese pigs displayed impaired glucose tolerance and hyperinsulinemia following glucose challenge, indicating that a metabolic phenotype developed with changes in body composition.  Consistent with obesity in humans, the gut microbiota of obese pigs displayed altered bacterial composition, but even more compelling differences in bacteriophage composition.  In the second study, we characterized the longitudinal changes in the gut microbiota in response to diet and aging in growing Mangalica pigs that were either limit fed a standard diet, allowed ad libitum access to a standard diet, or allowed ad libitum access to a high fat-supplemented diet over 18 weeks. Weight gain was highest in pigs fed the high fat diet compared to ad libitum and limit fed groups. The intestinal microbiota was generally resilient to differences in dietary intake (limit fed vs ad libitum), though changes in the microbiota of pigs fed the high fat diet mirrored changes observed in mature obese pigs. Also, bacteriophage populations within the gut microbiota responded rapidly to differences in diet, with significant compositional changes in bacteriophage genera observed between the dietary treatment groups as pigs aged. These studies are the first to describe the development of the intestinal microbiota in the Mangalica pig, and are the first to provide evidence that changes in body composition and dietary conditions are associated with changes in the microbiome of this novel porcine model of obesity.