A song of gut and bacteria


Breaking down the microbiology world one bite at a time

A song of gut and bacteria

Ever wondered why we eat, sleep, poop, and repeat at approximately the same time every day? This is because of our body’s biological clock. A number of factors can disrupt this clock. For example, when we travel to countries with different time zones, chaos unfolds for the first few days for our body in the new time zone (disrupted sleep pattern, fatigue, etc.) Gradually, the body adapts and we are back on track. This biological clock, also known as circadian rhythm, is partly controlled by a system existing in every cell of our body. The circadian rhythm is composed of several of these biological clock systems. 

One of such systems is diurnal oscillation which is a change in the body functions with the day/night cycle. Most intestinal epithelial cells follow this diurnal cycle. In response, the proteins produced by these cells also adapt to the diurnal cycle. The intestinal epithelial cells in our body produce regenerating islet-derived protein 3 gamma (Reg3γ) which is an Anti-Microbial Peptide (AMP). AMP targets specific microbes in our gut and keeps the otherwise friendly microbial inhabitants from crossing the intestinal epithelial barrier. If these microbes are able to cross the barrier, then our body is exposed to a myriad of infections (which is not pleasant at all!).

Do the microbial tenants of our body have the same rhythm?

It is natural that all other non-body cells residing in our body also adapt to the body’s rhythm. Non-body cells like gut microbes are intertwined with our body’s circadian rhythm and contribute to the constant functioning of our immune response pathways. Therefore, gut microbes are not alien to our body. However, if left unchecked these microbes can cross the intestinal barrier and cause infection in the organs which are not adapted to microbial presence. 

Working in sync with the circadian rhythm, gut microbes have a huge role in modulating host metabolic parameters [1, 2]. Recently, scientists have been working on an intriguing question: Do these microbes adapt to the diurnal rhythm of our body? While microbes have their own biological clock, they blend in this clock with the rhythm of their surrounding environment. But this is not straightforward. Specific microbes that can induce the synthesis of Reg3γ (e.g. Lactobacillus) can sing with the same rhythm as our body. However, this duet is only successful if supported by a fibre-rich low-fat diet. Microbes that induce Reg3γ tend to be resistant to the effect of Reg3γ themselves.

The scientists conducted an experiment on mouse models representative of human gut microbiota to understand if the levels of Reg3γ varied according to the mice diurnal cycle. They divided the mice into 2 groups: the first group was fed a low-fat diet (10% fat) and the second group was fed a high-fat diet (37.4% fat) (Figure 1).

After four weeks of feeding, the scientists harvested the intestine of the mice at specific timepoints in a 24-hour cycle (4 AM, 8 AM, 12 PM, 4 PM, 8 PM, 12 AM). They extracted the mucosal layer (inner sticky lining of the intestine). The mucosal layer prevents the gut microbes from crossing the intestinal barrier and reaching other organs of the body. During inspection of the levels of antimicrobial peptide transcript levels in this layer, scientists found that the Reg3γ transcripts were at their peak at 4 PM for low-fat diet fed mice, whereas the same was not true for the high-fat diet fed mice. In fact, Reg3γ levels remained unvaried across the 24-hour cycle for high-fat diet fed mice. 

Figure-1 : Experimental design of the study depicting two groups of mice fed (a) low-fat and (b) high-fat diet. Low-fat diet fed mice harboured Reg3γ-inducing Lactobacillus bacteria which oscillated with the same rhythm as the diurnal cycle of mice. High-fat diet fed mice did not show a similar trend. Image is created in BioRender.com. It is inspired by the graphical abstract of the original study.

To understand the change in the microbiota for the two groups of mice, scientists extracted the intestinal content from a specific part of the intestine: the ileum. The ileum is where most gut microbes colonise. They found significant differences in the relative amount of various bacteria in the ileum of low-fat diet and high-fat diet mice. 

In addition, they found that the abundance of Lactobacillus genera (which is known to induce Reg3γ) oscillated with the diurnal cycle of mice in low-fat diet fed mice (Figure 1). The scientists also found that a high-fat diet promoted growth of bacteria belonging to the Clostridiaceae and Peptostreptococcaceae family in the respective mice (Figure 1). These families are known to decrease in abundance in the presence of Reg3γ.

With this experiment, they concluded that the high-fat low-fibre diet leads to the expansion of a different set of microbes that do not induce the production of Reg3γ. Such an expansion increases the chances of opportunistic microbes crossing the intestinal barrier. This means more susceptibility to infections and in some cases, obesity followed by subsequent chronic health issues like diabetes.

What does this mean for us?

Our health, gut microbiota and body rhythm are intertwined with each other. So is our choice of the food that we eat daily. If our diet is not supplemented with the appropriate amount of nutrients and fibres, our body rhythm skips the beat and we get exposed to unwanted health issues. Therefore, we should be considerate about what we eat and when we eat. If our gut microbiota stays happy, so does our body rhythm. And the ultimate result? In addition to all the primary health benefits, a regular and satisfying poop cycle!

  1. Thaiss CA et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014 Oct 23;159(3):514-29. doi: 10.1016/j.cell.2014.09.048. 
  2. Leone V et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe. 2015 May 13;17(5):681-9. doi: 10.1016/j.chom.2015.03.006.

Link to the original post: Katya Frazier et al., High-fat diet disrupts REG3γ and gut microbial rhythms promoting metabolic dysfunction. Cell host & Microbe, June 2022.

Featured image: https://www.bionity.com/en/news/1169405/bacterial-cells-can-tell-the-time.html