CHICAGO—Up to 45% of species in the gut microbiome show substantial diurnal, seasonal and regional variations at the population level, according to a global analysis presented at Digestive Disease Week 2023. Based on the substantial oscillations in species during these time frames, this analysis appears to reveal a meaningful new variable with which to understand the microbiome composition.
The population-based fluctuations “have large implications” for attempts to understand microbiome composition in the context of disease, according to senior author Amir Zarrinpar, MD, PhD, a gastroenterologist and an assistant professor in the Division of Gastroenterology and Hepatology at the University of California, San Diego. In addition to the effort to connect dysbiosis to the risk for specific diseases, these fluctuations might explain susceptibility to seasonal diseases, such as upper respiratory infections or allergies.
Diurnal variations in the gut microbiome have already been demonstrated at the level of individual patients, but this is the first large study of globally collected samples.
Large Bank of Samples
Of nearly 20,000 human stool samples obtained from the American Gut Project (AGP)—the world’s largest repository of such samples—18,219 met the study criteria for analysis, including a time stamp for the hour of the day and day of the year when the sample was collected, according to Ana Carolina Dantas Machado, PhD, a researcher working in Dr. Zarrinpar’s lab, who presented the data at DDW (abstract 395).
The samples were provided by centers in multiple countries from 2013 through 2019. No more than 10 samples were obtained from any one patient. The samples were evaluated with a technique called cosinor-based rhythmometry, a method that looks for patterns in nonstationary data and is well suited to look for changes over short or long periods.
The investigators found diurnal and seasonal gut microbiome rhythms using the AGP data set, Dr. Machado reported.
Overall, 57% of phyla evaluated in the stool displayed diurnal cycling. Even after controlling for several variables, specific patterns of diurnal cycling were detected for more than 30% of organisms. For example, populations of Acinetobacter species on a population basis peaked in the evening, whereas populations of Synergistes peaked in the morning.
On a seasonal basis, Proteobacteria populations peaked in summer months in countries in the Northern Hemisphere, whereas Bacteroides peaked in the winter, but seasonal patterns overall were region specific. Some regional differences in gut microbiome fluctuations were independent of season.
Peeling Back the Onion
The study has no immediate clinical relevance, but Dr. Zarrinpar contended that it is an important piece of information as efforts to characterize the microbiome move forward.
This “new information is important” agreed Gary D. Wu, MD, a professor of gastroenterology at the University of Pennsylvania, in Philadelphia. Dr. Wu, who has published frequently on the microbiome, said the strengths of this study include the sample size and value of evidence showing daily and seasonal gut microbiome fluctuations at a population level.
Although diurnal and seasonal variations are likely an important part of the puzzle in understanding the gut microbiome, “it is very plausible that significant factors that influence the gut microbiome at an individual level will have a greater effect than the influence of diurnal or seasonal variations, but this will require further investigation,” he said.
Similarly, Mark Pimentel, MD, the executive director of the Medically Associated Science and Technology Program at Cedars-Sinai Medical Center, in Los Angeles, said he considers these data helpful for demonstrating yet another source of complexity in attempting to understand the gut microbiome in the context of pathogenicity.
But Dr. Pimentel questioned some of the methodology. While the investigators reported that “a diurnal variation in the microbiome was based on stool samples,” he said, “a stool sample provided at 5 o’clock in the afternoon is fundamentally different than one collected in the morning,” with afternoon samples being more likely to be associated with gastrointestinal dysfunction than those in the morning, which are more consistent with normal physiologic bowel rhythms.
If the goal is to define a normal gut microbiome by contrasting it with population-based studies, Dr. Pimentel said he doubts this is even feasible. “A definition of a normal microbiome will never happen. Our microbiomes differ by so many variables, including what we ate last night at dinner,” he said.
On a population basis, it is not yet understood what leads to fluctuations in the gut microbiome, but Dr. Zarrinpar said all of the usual suspects are likely to be relevant. They include diet as well as changes in pH induced by hydration, sleep or environmental factors such as humidity.
Consistent with previous data that demonstrated diurnal oscillations at the individual level, the evidence that this occurs at the population level is not entirely surprising, according to gastroenterologist Elena A. Ivanina, DO, MPH, of the Center for Integrative Gut Health, in New York City. Just as metabolic activity and diet affect the gut microbiome in the individual, she suggested one would expect seasonal factors, such as length of day and temperature, to also influence microbiome composition.
The findings “imply that in order to accurately compare microbiome tests and understand normal-versus-abnormal [results], the season and time of day need to be taken into consideration,” Dr. Ivanina said.
This study, along with ongoing research, “is needed to correctly identify what variables we need to know about microbiome testing to be able to characterize it accurately.”
—Ted Bosworth
Dr. Ivanina reported no relevant financial disclosures. Dr. Pimentel reported financial relationships with Bausch Health, Dieta Health, Ferring, Gemelli, GoodLFE, Progenity, Salvo Health and Theriva. Dr. Zarrinpar reported a financial relationship with Endure Biotherapeutics. Dr. Wu reported financial relationships with AbbVie, Biocodex, Danone, Intercept and Nestlé.
This article is from the September 2023 print issue.