Gut microbiome and metabolome modulation by maternal high-fat diet and thermogenic challenge

Authors: PAZ, HENRY - Arkansas Children'S Nutrition Research Center (ACNC); PILKINGTON, ANNA-CLAIRE - Arkansas Children'S Nutrition Research Center (ACNC); ZHONG, YING - Arkansas Children'S Nutrition Research Center (ACNC); CHINTAPALLISREE, V - Arkansas Children'S Nutrition Research Center (ACNC); SIKES, JAMES - Arkansas Children'S Nutrition Research Center (ACNC); LAN, RENNY - Arkansas Children'S Nutrition Research Center (ACNC); SHANKAR, KARTIK - University Of Colorado; WANKHADE, UMESH - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2022
Publication Date: 8/25/2022
Citation: Paz, H.A., Pilkington, A., Zhong, Y., Chintapallisree, V., Sikes, J., Lan, R.S., Shankar, K., Wankhade, U.D. 2022. Gut microbiome and metabolome modulation by maternal high-fat diet and thermogenic challenge. International Journal of Molecular Sciences. 23(17):9658. https://doi.org/10.3390/ijms23179658.
DOI: https://doi.org/10.3390/ijms23179658

Interpretive Summary: Dietary habits during and prior to pregnancy stages can program predisposition to excessive weight gain and associated complications. Maternal diets are known to influence gut microbiome and adipose tissue in babies. In the current study we investigated the effect of maternal diet on microbiome and adipose tissue. Beta-3-adrenergic stimulant (CL316243) was used to activate the brown fat. In summary, we showed that maternal high-fat diet (HFD) feeding not only impact microbiota but also associated metabolites produced from microbiome in offspring. Maternal HFD in combination with CL316243 treatment altered offspring’s microbial composition and function. Findings from this study contributes to the understanding of obesity at a molecular level, eventually which will help us design better ways to prevent obesity and related complication.

Technical Abstract: The gut microbiota plays a critical role in energy homeostasis and its dysbiosis is associated with obesity. Maternal high-fat diet (HFD) and ß-adrenergic stimuli alter the gut microbiota independently; however, their collective regulation is not clear. To investigate the combined effect of these factors on offspring microbiota, 20-wk old offspring from control diet (17% fat)- or HFD (45% fat)-fed dams received an injection of either vehicle or ß3-adrenergic agonist CL316,243 (CL) for 7 days and then cecal contents were collected for bacterial community profiling. In a follow-up study, a separate group of mice were exposed to either 8°C or 30°C temperature for 7 days and then blood serum and cecal contents were used for metabolome profiling. Both maternal diet and CL modulated the gut bacterial community structure and predicted functional profiles. Particularly, maternal HFD and CL increased the Firmicutes/Bacteroidetes ratio. In mice exposed to different temperatures, the metabolome profiles clustered by treatment in both the cecum and serum. Identified metabolites were enriched in sphingolipid and amino acid metabolism in the cecum and in lipid and energy metabolism in the serum. In summary, maternal HFD altered offspring’s response to CL and altered microbial composition and function. An independent experiment supported the effect of thermogenic challenge on the bacterial function through metabolome change.