Gut Microbiome Varies Hour to Hour, Month to Month

CHICAGO -- Composition of a person's intestinal microbial population differs from morning to night and from one month to the next, researchers found.

Analysis of more than 18,000 timestamped stool samples collected worldwide indicated that centered log-ratio values (a measure of relative abundance) for different bacterial phyla and families commonly found in the gut microbiome varied substantially over the course of a single day, and also over a full year, according to senior investigator Amir Zarrinpar, MD, PhD, of the University of California San Diego.

Populations of some phyla, such as Actinobacteriota, tended to peak in the afternoon and evening. Others, such as Proteobacteria, were more abundant in the morning, with troughs later in the day, Zarrinpar said at a press conference held in advance of the annual Digestive Disease Week conference, to be held here starting Saturday.

Thus, at one point in the day certain types of bacteria may predominate but a wholly different composition may appear a few hours later. "More than a third" of phyla analyzed showed some degree of diurnal cycling after adjusting for confounding variables, Zarrinpar said.

Similar patterns were seen across seasons: Proteobacteria hit their annual zenith in the summer and a winter trough, while a massive peak was found for Bacteroidota in late autumn and a nadir in late spring. The time plot for Verrucomicrobiota showed a double peak, in spring and again in the fall at a similar level.

Zarrinpar said seasonal variations in temperature, humidity, and other "environmental factors" likely drive these changes, with different types of bacteria responding in their own peculiar ways.

With regard to diurnal cycling, he cited such influences as "nutrient and water availability and sleep" as important factors.

He also speculated that these previously unsuspected shifts in gut bacteria might help explain why people don't all respond to a particular drug in the same way, insofar as the microbiome is important in metabolizing them (and can affect organ function in other ways as well).

"As physicians and as scientists, we always wonder why certain patients respond more robustly to some medications than others. I think that in terms of performing clinical trials, it's important to remember that -- especially if it's a wide-ranging, multiyear study -- that perhaps there may be seasonal variations in response to a drug, and if so, it may be affected by something [like] the relationship of the microbiome, the host immune system, or post-metabolic processes," Zarrinpar said at the press conference.

"For example, an interesting thing we've thought about is that patients' responses to COVID vaccines differs by what time of day they receive the vaccine. Certainly since the microbiome is a tremendous influencer of immune response, we do wonder whether these variations [in microbiome composition] have a role in something like vaccine response."

Microbiome variations might also account for seasonal increases and decreases in susceptibility to infections, he said.

He cautioned that "it's too early" to conclude definitively that microbiome variation drives drug and vaccine responses, but it clearly deserves more study.

Stool samples were collected as part of the American Gut Project, a "citizen science" program in which individuals voluntarily submit dry-swab samples through the mail. Almost 100,000 have entered the project's database so far -- "primarily from Western countries" and in the Northern Hemisphere, according to Zarrinpar -- mostly collected from 2013 to 2019. The 18,219 included in the current study were those with day and time of collection recorded, and with at least 200 bacterial counts per sample. No more than 10 samples from any individual were allowed, and those from children or adolescents were excluded.

Zarrinpar also noted at the press conference that the data show some regional and ethnic differences in the diurnal cycling patterns. Those data were not presented in detail or included in the abstract published before the conference.

He also indicated that an important direction for future research is to examine whether the diurnal and seasonal variations correlate with individuals' health status.

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