Circadian disruption changes the microbiome and causes leaky gut

From the inception of this blog my goal was to illustrate to people the importance of lifestyle for maintaining a healthy gut.  I feel people put too much focus on things like probiotic and prebiotic supplementation and not enough on lifestyle factors.  I also think most people get the idea that diet matters, but other than that lifestyle is completely ignored.

Part of this comes from the fact that people believe the microbiome causes issues.  I don’t think this is an accurate representation of what the data shows.  Rather, I believe the microbiome is a biomarker of lifestyle factors that increase disease risk.  So, instead of a microbial set causing Type 2 diabetes, I believe it’s more accurate to say that a microbial set is indicative of a lifestyle that leads to Type 2 diabetes.

There’s obviously more hope for people believing they can supplement their way to a healthier microbiome which will, in turn, reverse their disease.  Unfortunately, again, this isn’t an accurate perception of the data.  People with circadian disruption, poor sleep, who are sedentary, and eat a poor diet have a microbial signature that predisposes them to Type 2 diabetes, but changing the microbiome requires changing lifestyle, not popping pills or powders.

A study recently published in Frontiers of Microbiology backs up this notion, and may finally be putting a spotlight on the potential for circadian disruption to wreak havoc on the gut.

Circadian rhythms and the microbiome

Most people understand that there is bi-directional communication between the gut and the microbiome.  In addition, the microbiome has a circadian rhythm that likely has a bi-directional relationship with our circadian rhythm.  This process involves at least the gut and the liver, and likely the brain.  Ultimately, everything probably matters to some extent.

You don’t need a deep understanding of the biology to understand the implications of this bi-directional relationship.  The microbiome is known to participate in numerous biological processes in humans, including immune system response, intestinal barrier integrity, and host metabolism.

During its circadian rhythm, the microbiome takes its cues from our circadian rhythm, with the numbers of different species waxing and waning throughout the day.  Circadian variation in different hormones, enzymes, and metabolites such as cortisol, bile and melatonin tell the microbiome what time it is and this adjusts how the microbiome interacts with the gut to promote healthy gut function.

So what happens if the host’s rhythm is messed up?  Well that takes us to the study…

Mice, circadian disruption, and the microbiome

Eating at irregular times is known to affect the microbiome, and in turn, the host.  There is ample data on the beneficial effects of time-restricted feeding in mice.  But what happens if we impose circadian disruption in a different way?  What if we just leave the lights on and see what happens?  So they took 2 sets of mice, one with a normal 12 hours on/12 hours off exposure to light and another with 24 hours of constant light, and followed them for 4 weeks.

Interestingly enough, a lot seems to happen.  For one, diversity dropped.  This would disrupt the master clock which would have a knockdown effect on all of the peripheral clocks.  This leads to a change in so many factors that help synchronize the clocks including cortisol, insulin, melatonin, bile acid synthesis and release and so on.

But that’s not all that happened.  Ruminococcus torques, a species that degrades the mucus layer and is associated with IBS, increased in abundance by 50%.  Abundance of Lactobacillus johnsonii decreased by more than 60%.  L. johnsonii is a beneficial strain that modulates the immune system and promotes integrity of the intestinal barrier.

Other strains were affected as well, but these were just trends as the sample size was small.  Gut health took a major hit as butyrate production decreased, indole metabolism decreased, and lipopolysaccharide production and transport was increased.  Overall, mice under circadian disruption had leaky guts, higher LPS levels, and more inflammation than those exposed to normal lighting conditions.

Relevance to humans

It may not seem like there’s much relevance to humans here, but there is.  The constant lighting conditions that the mice lived under was artificial, not unlike the constant lighting exposure most people working in offices experience.  Between the office and artificial lighting at home, most people spend at least 15 hours every day exposed to artificial lighting.

Our circadian clocks use the day/night cycle to set rhythms that regulate intestinal permeability, inflammation, bile output, and immune function.  Other factors too, such as the feeding/fasting cycle and timing of physical activity, play a role in helping our biology determine when is the best time to tamp down inflammation or maintain intestinal barrier integrity.  When we’re exposed to abnormal lighting conditions, irregular meal times, or oddly timed physical activity, this can throw the timing off and cause problems.

How these things are layered also plays a role.  You may follow a feeding/fasting cycle that’s appropriate in length, but having a feeding/fasting cycle of appropriate length placed during the inactive period disrupts the circadian rhythm in bile output.  Something to put in to perspective, most humans living a modern lifestyle eat the bulk of their calories during their inactive period, after work.

Conclusion

While we have yet to determine if the microbiome causes disease or is just a biomarker of a lifestyle that leads to disease, this study seems to be pointing to the latter rather than the former.  Both groups of rats were fed the same food and provided ad libitum access to it while being housed in separate cages, so it’s extraordinarily unlikely that exposure to bacteria caused the changes between groups.

Unfortunately, they didn’t record feeding, sleeping, or physical activity times in this study.  I would have loved to see if exposure to different lighting schemes leads to differences in timing or quantity of food intake, sleep, or physical activity.

Regardless, it’s quite obvious from this study that people working for optimal gut health need to begin worrying more about things other than what’s in their diet.  Particularly if they’re trying to improve their microbiome or fix leaky gut.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s