Intrinsic aerobic capacity governs the associations between gut microbiota composition and fat metabolism age-dependently in rat siblings

Abstract

Host genetic factors affecting the gut microbiome play an important role in obesity, yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity, while in older adult (hereafter old) rats most of the differences between the lines associated with body weight. Despite the absence of weight differential between LCR and HCR when young, the LCR microbiome contained more Actinobacteria, Veillonellaceae, Coriobacteriaceae, Phascolarctobacterium, and Ruminococcus; taxa previously linked to obesity. This raises the question whether the microbiome contributes to the later development of obesity in LCR. Age-related differences were detected in almost all taxa in both rat lines. The young HCR measured higher for serum glycerol and free fatty-acids and lower for cholesterol, HDL, LDL, and triglycerides than LCR. The old HCR differed from the old LCR by lower LDL. Several metabolites, including LDL, are associated age and genetic background-dependently with the microbiome, which might explain the metabolic differences between the lines. While old lines did not differ in visceral adipose tissue gene expression, the young HCR expressed more inflammatory genes than LCR, and several taxa including Proteobacteria associated with these genes. In conclusion, intrinsic aerobic capacity governs the microbiome, which may influence body weight, metabolism, and gene expression.

Keywords: gene expression; gut microbiota; intrinsic aerobic capacity; lipid metabolism.

Fig. 1.

Phylum-level abundance of gut microbiota in young and old high-capacity running (HCR) and low-capacity running (LCR) rats. We included 9 young HCR, 10 young LCR, 12 old HCR, and 10 old LCR in the 16S rDNA sequencing. All data are presented as means ± SD. The statistical significance was set to P < 0.05, and the significant differences are presented with lines and * between the groups. The young HCR rats differed from LCR rats by harboring less Actinobacteria. The old HCR rats differed from LCR rats by harboring less Bacteroidetes and more Spirochaetes and Deferribacteres.

Fig. 3.

Genus-level abundance of gut microbiota in young and old HCR and LCR rats. We included 9 young HCR, 10 young LCR, 12 old HCR, and 10 old LCR in the 16S rDNA sequencing. All data are presented as means ± SD. The statistical significance was set to P < 0.05, and the significant differences are presented with lines and * between the groups. The young HCR harbored less Phascolarctobacterium and Ruminococcus, and more genus Lactobacillus than the young LCR. The old HCR had more genera Prevotella of the Paraprevotellaceae family, Mucispirillum and Treponema, and less genera Phascolarctobacterium and unknown genera of Erysipelotrichaceae than the old LCR.

Fig. 2.

Family-level abundance of gut microbiota in young and old HCR and LCR rats. We included 9 young HCR, 10 young LCR, 12 old HCR, and 10 old LCR in the 16S rDNA sequencing. All data are presented as means ± SD. The statistical significance was set to P < 0.05, and the significant differences are presented with lines and * between the groups. The young HCR had less Veillonellaceae and Coriobacteriaceae than young LCR. The old HCR had more families Spirochaetaceae and Deferribacteraceae than the old LCR.

Fig. 4.

Significantly differing taxa between young and old HCR rats. We included 9 young HCR and 12 old HCR in the 16S rDNA sequencing. The data are presented as an average of each group.

Fig. 5.

Significantly differing taxa between young and old LCR rats. 10 young LCR and 10 old LCR were included in the 16S rDNA sequencing. The data are presented as an average of each group.

Fig. 6.

Visceral adipose tissue inflammatory gene expression in young and old HCR and LCR rats. We included 9 young HCR, 10 young LCR, 12 old HCR, and 10 old LCR in the 16S rDNA sequencing. All data are presented as means ± SD. The statistical significance was set to P < 0.05, and the significant differences are presented with lines and * between the groups. The young HCR rats expressed more IL1B and CD45 but less AdipoQ and TLR5 than LCR. In old rats no mRNA expression differences between the lines were found.

Fig. 7.

Main findings of the study. Several microbial taxa in young rats were linked to inherited aerobic capacity, while in old adult rats most of the differences between the lines may be influenced by body weight. Despite the lack of weight difference between the younger rat lines, LCR had more Actinobacteria, Veillonellaceae, Coriobacteriaceae, Phascolarctobacterium and Ruminococcus, which have been previously linked to obesity. Young HCR expressed more inflammatory genes than LCR in the visceral adipose tissue. The young HCR measured higher for serum glycerol and free fatty-acids (FFA) and lower for cholesterol (chol), HDL, LDL, and triglycerides (trigly) than LCR. The old adult HCR differed from the old adult LCR by lower LDL.