Aging effects on the diurnal patterns of gut microbial composition in male and female mice

Abstract

Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.

Keywords: Aging; Diurnal rhythm; Dysbiosis; Gut microbiota; Sex difference.

Fig. 1. Diurnal differences of the gut microbiota between young and aged mice at the phylum and family levels.

(A) Experimental scheme of gut sampling times in young and aged mice according to light/dark cycle. (B–E) Mean gut microbiota values of cecum collected at 10 AM (AM) and 10 PM (PM) samples of young and aged male mice at the phylum level. (B) Stacked bar chart of microbiota composition of phyla present at > 1% relative abundance of male mice. (C) Firmicutes to Bacteroidetes (F/B) ratio of male mice. (D) Relative abundance of Verrucomicrobia of male mice. (E) Relative abundance of Cyanobacteria of male mice. (F) Stacked bar chart of microbiota composition of phyla present at > 1% relative abundance of females. (G) F/B ratio of female mice. (H) Relative abundance of Verrucomicrobia of female mice. (I–K) Mean gut microbiota values of AM and PM cecum samples of young and aged mice at the family level. (I) Stacked bar chart of microbiota composition of families present at > 1% relative abundance of male mice. (J) Stacked bar chart of microbiota composition of families present at > 1% relative abundance of female mice. (K) Relative abundance of Sutterellaceae of female mice. n = 3/group, *p < 0.05.

Fig. 2. Diurnal differences of gut microbiota between young and aged mice at the genus level.

(A–D) Mean gut microbiota values of cecum collected at 10 AM (AM) and 10 PM (PM) samples of young and aged male mice. (A) Relative abundance of Rikenella. (B) Relative abundance of Rikenellaceae RC9 gut group. (C) Relative abundance of Lachnospiraceae NK4A136 group. (D) Relative abundance of Ruminococcaceae UCG-014. (E–I) Mean gut microbiota values of AM and PM cecum samples of young and aged female mice. (E) Relative abundance of Alloprevotella. (F) Relative abundance of Lachnospiraceae NK4A136 group. (G) Relative abundance of Lachnospiraceae UCG-001. (H) Relative abundance of Ruminiclostridium. (I) Relative abundance of Parasutterella. n = 3/group, *p < 0.05.