PNNL

The Science

Most organisms on Earth, from animals to bacteria, exhibit strong biological rhythms. In animals, every organ and even every cell display (near-)24-hour oscillations known as circadian rhythms. Gut bacteria are already known to modulate various essential host processes, and there is evidence to suggest a relationship with host circadian rhythms. Daily oscillations in the gut microbiome have been assessed using composition, abundance, and metabolite measurements. The extent of functional rhythmicity of the microbiome must be established to understand interactions with host rhythms. This study profiled the 24-hour rhythmicity in bile salt hydrolase enzyme activity using simple fluorescence assay and the results showed that this rhythmicity is influenced by feeding patterns of the host.

The Impact

Approximately 20 percent of U.S. jobs require shift work, which leads to frequent circadian disruption and increases workers’ risk of developing a variety of diseases. As the microbiome displays functional rhythmicity, these disruptions likely impact rhythmic processes in the host. It is crucial for scientists to understand which functions of the microbiome are rhythmic, how these rhythms interact with the host, and which are subject to manipulation. Such knowledge will allow for the development of robust intervention strategies for those whose occupations require atypical sleep schedules. Scientists from Pacific Northwest National Laboratory foresee that function-focused assays will be key to driving future strategies for coping with circadian disruption. PNNL’s novel function-centric approach has potential to aid in the discovery of therapeutic, diet, or lifestyle interventions for correction of circadian perturbations linked to bile metabolism.

Summary

Diurnal rhythmicity of cellular function is key to survival for most organisms on Earth. Many circadian functions are driven by the brain, but regulation of rhythms in peripheral organs remains poorly understood. The gut microbiome is a potential candidate for regulation of host peripheral rhythms, and new research done by PNNL published in Organic & Biomolecular Chemistry specifically examines the process of microbial bile salt biotransformation. To enable this work, the research team developed a rapid and inexpensive assay to detect bile salt hydrolase (BSH) that could work with small quantities of stool samples. The research team successfully applied this assay to detect significant BSH activity in small amounts of mouse fecal/gut content within a short time frame, which illustrates its potential for use in various biological/clinical applications. Using this assay, the team investigated the diurnal fluctuations of BSH activity in the large intestine of mice. By using time restricted feeding conditions, the study provided direct evidence of 24-hour rhythmicity in microbiome BSH activity levels and showed that rhythmicity is influenced by feeding patterns. This novel function-centric approach has potential to aid in the discovery of therapeutic, diet, or lifestyle interventions for correction of circadian perturbations linked to bile metabolism.

PNNL Contact

Chathuri J. Kombala, chathuri.kombala@pnnl.gov, PNNL

Funding

Research was supported in part by the Biopreparedness Research Virtual Environment (BRaVE) grant and the Earth and Biological Systems Directorate Laboratory Directed Research and Development (LDRD) program at PNNL, which is operated by Battelle for the Department of Energy.