Although recent research in humans has found that the gut microbiota follows a circadian rhythm in vitro and responds to fluctuations in the hormone melatonin, further studies in humans related to the circadian rhythms in vivo are necessary and the exact mechanisms accounting for the observed bacterial rhythms have not been shown yet. Moreover, the impact of timing of food intake on microbiota in humans has not been investigated. Considering the evident difficulties immerse in analysing the circadian rhythm of gut microbioma in vivo, oral microbiome is an appropriate alternative to address this questions. Indeed, a recent publication in Science has demonstrated that exogenous oral microbiome is able to impact inflammation in the gut and to influence inflammatory diseases such as Crohn´s Disease. Nevertheless, the impact of food timing on daily rhythms of oral microbiota in humans is unknown.

A recent study, led by Dr. Marta Garaulet (Department of Physiology, University of Murcia, Murcia, Spain), has found that meal timing affects the daily rhythm of the human salivary microbiota and that timing differences may have a deleterious effect on the metabolism of the host.

María Carmen Collado and Marta Garaulet, co-authors of the study, corresponded with GMFH editors about the significance of the work.


What do you know so far regarding the relationship between the microbiota, metabolic homeostasis and the timing of food consumption?

Our previous results have demonstrated that the timing of food intake is a predictor of total weight loss not only in a dietary treatment but also after a surgical process in severe obesity. However, the physiological and metabolic bases of this process are still not well studied; moreover, the potential implications of microbiota have not been studied. We hypothesized that several aspects related to the time of eating can impact microbiota and could be one of the mechanisms for late-eating-induced metabolic dysfunction.

This is the first study where the role of timing of food consumption towards the microbiota changes in a healthy population, in relation to obesity development, has been addressed.

A multidisciplinary team from different countries and institutions and research areas, such as nutrition, food science, chronobiology, biomedicine etc. were collaborating to make it possible.

Briefly, what study protocol did you use in order to assess the impact of meal timing (eating either early -lunch at 1400 h- or late -lunch at 1730 h) on the human microbiota from saliva.

We conducted a randomized, crossover interventional study in healthy non-obese participants. Each participant (n=18) was studied under two food timing conditions: In the early eating condition (EE) lunch was taken at 14:00; while in the late eating condition (LE) lunch was taken at 17:30. All participants were given the same controlled diet with three standardized meals (breakfast, lunch and dinner) during these two 7-day experimental periods. To determine if eating late alters daily rhythms of human salivary microbiota, we measured salivary microbiota in samples obtained at four specific time points over 24 hours in order to achieve a better understanding of the relationship between food timing and metabolic alterations in humans.

What are the most relevant results of your study and what is its clinical significance?

The main results may be divided in three blocks: a) the existence of significant diurnal rhythms in salivary diversity and bacterial relative abundance (i.e., TM7, also known as the phylum candidatus Saccharibacteria and Fusobacteria) across both early and late eating conditions; b) the observation that food timing affected diurnal rhythms in diversity of salivary microbiota towards an inverted rhythm between the eating conditions; and c) the observation that eating late increased the number of putative pro-inflammatory taxa showing a diurnal rhythm in the saliva.

Our results are exciting as we observed changes in bacterial diversity and composition in normal weight and healthy women by just changing the lunch time during a short period, only one week. Those observed changes in late eating conditions were similar to the ones reported in other studies with obese and diabetic people, and also support the previous data (here; here) obtained by Garaulet team. We demonstrated that eating late affects not only body weight, cortisol rhythm, basal metabolic rate, glucose tolerance and body temperature profile, but also the oral microbiota profile.

To what extent does the human salivary microbiota reflect the composition and functional diversity of the human gut microbiota? Do you think the human salivary microbiota could be used as a specific and sensible biomarker related to nutritional status of the host?

We are still far from understanding what defines a healthy microbiome. Many studies are related to gut microbiome but information on oral microbiota and its role in health is needed. The oral cavity serves as an initial digestive organ and it is populated by specific microorganisms with defined functions.

What further steps is your research group planning to take in the way of studying oral microbiota rhythms as a potential biomarker for risk of metabolic disorders and also as a therapeutic target for obesity and metabolic syndrome?

We think that the early identification of potential biomarkers… including serotonin, individual chrono-type, genetic polymorphisms of clock genes, or psychological factors such as emotional eating or motivation, as well as microbes, may represent a possible way to identify people with increased risk to develop overweight, obesity and related problems later in life. Although our findings need to be confirmed in larger cohorts, both healthy and obese, it paves the way to develop preventive strategies, including those aiming to modulate the microbiota. This would help us to identify potential responders and non-responders to specific interventions. Also, it would be of great interest to detect which factors in infant population would be modulated through food timing in order to reduce the risk of disease. This aspect is also something we are planning to investigate in combination with obese populations.



Collado MC, Engen PA, Bandín C, et al. Timing of food intake impacts daily rhythms of human salivary microbiota: a randomized, crossover study. FASEB J. 2018. doi: 10.1096/fj.201700697RR.