“You are what you eat” has long been used to describe the gut microbiome, but new research from the Perelman School of Medicine at the University of Pennsylvania shows that not only what you eat, but also who eats and when they eat, can shape the microbiome. The study, published online in the Early Edition of the Proceedings of the National Academy of Sciences (PNAS), reports that the abundance and composition of gut bacteria in mice follow a 24-hour circadian rhythm that is strongly influenced by the host’s internal clock and differs between sexes—particularly showing greater rhythmicity in females.
Circadian rhythms govern many physiological, metabolic, and behavioral processes in mammals, aligning internal functions with daily light–dark cycles. Recent investigations into the gut microbiome reveal that gut bacteria themselves exhibit circadian patterns linked to host behaviors such as feeding time. However, the mechanisms linking host circadian machinery, sex, feeding, and microbiome variation have not been fully clarified until now.
Doctoral student Xue Liang, working with the laboratories of Garret A. FitzGerald, MD, FRS, and Frederic Bushman, PhD, analyzed circadian fluctuations in the gut and fecal microbiota of mice using deep genetic sequencing techniques. The researchers quantified both absolute bacterial abundance and the relative composition of taxa across the 24-hour cycle. They observed pronounced daily oscillations in the absolute numbers of fecal bacteria and in the abundance of the major bacterial group Bacteroidetes. These oscillations were especially clear in female mice compared with males.
During the light phase—when laboratory mice are typically resting and ingesting less food—Bacteroidetes tended to predominate, reaching peak abundance toward the end of the light period. The investigators suggest that feeding behavior and the resulting availability of dietary nutrients influence bacterial dynamics: when dietary carbon sources are scarce during resting periods, some strains of Bacteroidetes are able to exploit host mucus-derived carbon, allowing them to flourish at times when feeding is reduced.
To test whether these daily patterns depend on the host circadian clock, the team disrupted the central clock gene Bmal1. Deletion of Bmal1 eliminated the 24-hour rhythmicity in fecal microbiota composition in both male and female mice. Loss of Bmal1 also altered overall bacterial abundances in feces, with effects that varied by sex. Although both sexes normally displayed circadian variability in microbiome composition, females exhibited stronger oscillations. Importantly, however, disrupting the molecular clock erased these rhythms regardless of sex, indicating that the host circadian system is the dominant driver of microbial rhythmicity while sex acts as a modifying factor.
“While feeding time and other host behaviors clearly influence these interconnected cycles, our data demonstrate that biological sex interacts with the circadian clock to shape the daily rhythmicity and composition of fecal microbes in mice,” says lead author Xue Liang. The authors emphasize that future microbiome research should account for circadian timing and host sex when designing experiments and interpreting data. They also highlight the value of measuring absolute bacterial abundance—beyond relative proportions—to better understand how microbiome dynamics may affect host physiology and conditions such as inflammatory bowel disease.
Funding: This research was supported by the National Heart, Lung, and Blood Institute (grant 1U54HL117798).
Source: Karen Kreeger, Perelman School of Medicine, University of Pennsylvania.
Image source: Photo credited to Rasbak (image used for illustration).
Original research: Xue Liang, Frederic D. Bushman, and Garret A. FitzGerald, “Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock,” published online in PNAS. The study analyzed deep sequencing data from mouse fecal microbiota to show that both absolute abundance and taxonomic composition of gut bacteria follow circadian rhythms that depend on the host molecular clock and differ between sexes.
Abstract
Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock
Many mammalian physiological and metabolic processes follow circadian rhythms that adapt to daily light cycles. Using deep-sequencing analysis of mouse fecal microbiota, the investigators found that absolute fecal bacterial counts and the abundance of Bacteroidetes display circadian rhythmicity, more prominently in female mice. Disruption of the host circadian clock via deletion of Bmal1 abolished microbial rhythmicity in both sexes and altered bacterial abundances with sex-dependent effects. These results indicate that sex and the host molecular clock interact to shape the daily rhythmicity and composition of the gut microbiota in mice.