Association of Colonic Bacterial Composition with Host Physiology is Dependent on Dietary Fat Quality and Sex in Aging CD‐1 Mice
Authors: Unger Allison L , Jetton Thomas L , Kraft Jana 
Published: June 2021

Colonic bacterial composition is critical in the development of metabolic diseases, yet, the significance of specific bacterial taxa in disease risk, pathogenesis, and prevention is not well defined. While it is known that diet, sex, age, and genetic makeup of the host can influence colonic bacterial composition, how these factors interact with the bacteria to affect host physiology is poorly understood. Our study utilized the genetically heterogeneous CD‐1 mouse stock to determine the effect of long‐term dietary fat quality (i.e., fatty acid composition) and sex on colonic bacterial composition (relative abundance and diversity) during aging. For 13 months, starting at the age of four weeks, male and female mice were fed one of four isoenergetic (40% total energy) diets: i) Control, U.S. fat blend (CO; representing the dietary fat quality of the average U.S. American); ii) CO fat blend displaced with 30% fish oil (FO); iii) CO fat blend displaced with 30% dairy (butter) fat (BO); and iv) CO fat blend displaced with 30% echium oil (EO). Feed intake and body weight were measured weekly and monthly, respectively. Glucose and insulin tolerance tests (GTT and ITT, respectively) were performed every three months to assess glucose homeostasis and insulin resistance. Individual fecal samples were collected via metabolic cages at 10.5 months of age (i.e., mid‐life in life course) and 13.5 months of age (i.e., aged period in life course; post‐reproductive senescence). Multivariate Spearman correlations were used to determine associations between colonic bacterial composition and glucose homeostasis and insulin resistance. At mid‐life, relative abundance of Alistipes was positively correlated with weight gain in FO‐fed (r = 0.83; P < 0.05) and BO‐fed (r = 0.76; P < 0.05) mice, whereas the relative abundance of Parabacteroides was positively correlated with weight gain in EO‐fed mice (r = 0.68; P < 0.05). In aged mice, the abundance of Allobaculum and Anaerostipes was associated with improved glucose tolerance in BO‐fed mice, as determined by a reduction in GTT area under the curve (AUC; r = −0.65 and r = −0.58, respectively; P < 0.05). In addition, alpha diversity (Chao1) was associated with improved glucose tolerance (via GTT AUC) in aged EO‐fed mice (r = −0.74; P < 0.05). In females, a negative correlation was found between the relative abundance of Roseburia and Barnesiella and fasting plasma glucose at mid‐life (r = −0.51; P < 0.05) and aged (r = −0.58; P < 0.01) life stages, respectively, indicating that these bacterial taxa may contribute positively to glucose homeostasis. Yet, only in aged males, the abundance of Lactobacillus was correlated with improved fasting plasma glucose (r = −0.65; P < 0.01). Our study suggests that dietary fat quality and sex modulate the association of specific colonic bacterial taxa and metabolic risk factors in CD‐1 mice, and that the effects of certain colonic bacteria on host physiology may change with age of an individual.Support or Funding InformationArmin Grams Memorial Research Award, UVM Robert Larner, M.D. College of Medicine; USDA‐NIFA Hatch Fund (accession number: 1006628).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.