“For a dinner date, I eat light all day to save room, then I go all in: I choose this meal and this order, and I choose you, the person across from me, to share it with. There’s a beautiful intimacy in a meal like that.”
~Anthony Bourdain
Rhythms.
They are everywhere in Nature.
They extend from our everyday experience into the quantum realm, where molecules resonate with a particular frequency. The molecules that form the basis of our meals are no exception, with each particle demonstrating a unique vibrational fingerprint. What we perceive as “minty freshness” is actually a gaggle of organic molecules such as α-pinene, β-pinene, β-myrcene, limonene, menthone, isomenthone, menthyl acetate, neomenthol, β-caryophyllene, menthol, pulegone, and piperitone with individual and unique vibrational voices acting as a collectively refreshing chorus.[1]
The bacteria in our gut are no more an exception to this ebb and flow of Nature’s oscillations than the sea; like the tides and times, they wait for no man. It has been well established that the gut microbiome exhibits a diurnal rhythm, or a 24-hour cycle. Various factors that disrupt the cycle, such as the consumption of xenobiotics (covered in a previous column), which are a common constituent of ultraprocessed foods, contribute to metabolic dysfunction. This, in turn, can result in chronic disabilities and diseases (CDD) like type II diabetes and cardiovascular disease.
In addition to changing what we eat to address the current epidemic of CDD, strategies like intermittent fasting – generally referred to as time-restricted feeding or TRF – employ when we eat as another treatment variable. In mouse models, TRF has been shown to mitigate insulin resistance, adiposity, and inflammation – the hallmarks of type II diabetes – that result from a high-fat diet, whilst at the same time resetting circadian gene expression and bile acid metabolism.
A recent study utilizing a murine model examined this impact of time, in addition to the more traditional compositional data, in an effort to more completely describe the dynamic functional landscape that is the gut microbiome.
- The study profiled the cecal gut microbiome of diet-induced obese mice (DIO) consuming a high-fat diet under both ad libitum and TRF conditions.
- Metatranscriptomics (the study of the transcriptional profile of a microbial community) reveals diurnal functional shifts missed by metagenomics; it profiles RNA transcripts, which reflect real-time functional states[2].
- The mice were observed for 8 weeks and:
- Mice that consumed a high-fat diet ad libitum exhibited signs of metabolic dysfunction.
- The mice that consumed a high-fat diet under TRF conditions did not exhibit the adiposity, inflammation, and insulin resistance seen in the high-fat ad libitum group and demonstrated improvements in glucose homeostasis and the partial restoration of the daily microbial rhythms absent in the mice with unrestricted access to a high-fat diet; although TRF did not fully restore the complete normal rhythmicity of the control mice.
- Time-restricted feeding (TRF) restores microbial transcript cycling under a high-fat diet, suggesting that diet strongly shapes the microbial functional landscape and that TRF promotes distinct, feeding-dependent shifts in microbial activity—detectable only through metatranscriptomics.
- Dubosiella newyorkensis bsh1 (DnBSH1) exhibits unique diurnal expression under TRF conditions.
- Administration of E. coli genetically engineered to express DnBSH1 improved mouse metabolic health with increased lean muscle mass, less body fat, lower insulin levels, enhanced insulin sensitivity, and better blood glucose regulation.
The Caveat:
Jean Anthelme Brillat-Savarin, the French gastronome and author of The Physiology of Taste, wrote in 1825, “Dis-moi ce que tu manges, je te dirai ce que tu es,” which translates as “Tell me what you eat, and I will tell you what you are.” What he failed to disclose or was unaware of at the time is that it is not just the “what” but also the “when” of eating – or not – that can impact your health. This emerging field of study, known as chrononutrition, adds the inescapable complexity of time to our individual food-health relationship, thereby strengthening the growing connections between our dining environment, our food, and our health.
This murine study suggests that subtle alterations to our diet, such as the timing of meals, can significantly impact our functional metabolic state. “In mice, [their] microbial rhythms are well-aligned with their nocturnal lifestyle. For example, during their active (nighttime) period, certain beneficial microbial activities increase, helping digest food, absorb nutrients, and regulate metabolism…We chose an 8-hour feeding window based on earlier research showing this time period allows mice to consume the same total calories as those with unlimited food access. By controlling [the] calories in this way, we ensure any metabolic or microbial benefits we observe are specifically due to the timing of eating, rather than differences in total food intake,” said Dr. Zarrinpar, lead researcher of this study.
The information processing of our gut bacteria reflects the workings of our DNA; the mere presence of a gene (as determined by metagenomics, which is most commonly used as a biological marker) does not reliably predict gene expression. It is the functional network of genes, what is turned on and off, and when the switches are activated, along with the post-processing of the proteins these genes code for, that drive metabolic health or illness. Our dining environment impacts all of these processes through epigenetic interactions.
This study is particularly relevant in that it provides pathways for solutions. When mice are made obese by feeding them a high-fat diet, the regular diurnal rhythm of the gut microbiome is thrown askew. Without changing the diet, but by simply adjusting the time interval between meals, the rhythm of the gut returns to normal. This is important because many gut microbiome studies that examine the effects of various interventions often neglect the time component in their experimental design and analysis. This is a principle that timing affects the transcription, known as host transcriptomics, which can critically impact physiological outcomes.
By manipulating host transcriptomics through the genetic alteration of E. coli bacteria to produce specific bacterial products (in this case, a product usually produced by the bacterium D. newyorkensis), a door opens to metatranscriptomics. An opportunity to uncover microbial enzymes with distinct substrate profiles and regulatory properties shaped by diet that can be used to restore normal gut physiology and function. In this study, mice colonized with the genetically altered E. coli exhibited improved glucose regulation, enhanced insulin response, reduced fat mass, and increased lean mass, all without the need for TRF. In other words, because the genetically engineered E. coli bacteria continually expressed the enzyme DnBSH1, which is usually produced by D. newyorkensis, the mice received all the benefits of TRF without having to adhere to the regimens of a TRF schedule.
Although pregnant with possibilities, it is always essential to remember that mice are not humans and that such findings must always be considered with caution.
[1] This field of study, generally referred to as quantum biology, remains controversial.
[2] With short half-lives and high responsiveness to environmental cues, metatranscripts enable detection of rapid microbiome shifts that are often missed by DNA-based methods.
The Study:
Additional references: