Is chronic fatigue syndrome caused by leaky gut & circadian disruption?

Chronic fatigue syndrome(CFS) is a condition characterized by excessive fatigue with no other underlying condition. Reactivation of latent viral infections is one of the proposed mechanisms behind CFS. However, it may only be causal in a subset of people with the condition

There are several latent viruses that, when awoken, cause CFS. I recently covered some recent evidence that circadian disruption may contribute to Epstein-Barr virus reactivation. Turns, out there’s a lot more evidence to support the idea that circadian disruption reactivates latent viruses.

Normally, in a healthy person with a strong immune system, latent viral infections remain…latent. Essentially, the immune system keeps them at bay. But in an immunocompromoised person, reactivation of the virus occurs. This is exactly how the chicken pox virus remains latent for years, but causes shingles decades later.

The problem is, shingles normally happens when we are older and immune function declines. But chronic fatigue happens at many ages. So age-related immune decline isn’t the culprit here. It appears circadian disruption might be the cause.

How circadian disruption leads to chronic fatigue

You don’t have to be over 65 to experience an impaired immune system. People with Type 1 & 2 diabetes have an impaired immune system. This is somewhat odd because they present, at least initially, with opposing changes in the hormone insulin.

In Type 1 diabetics, an autoimmune attack destroys insulin producing cells in the pancreas. As a result, insulin levels hit the floor. On the other hand, type 2 diabetics initially present with high insulin levels. Many behaviors contribute to Type 2 diabetes including:

  • A high calorie diet
  • Low fiber intake
  • Lack of physical activity
  • Central adiposity
  • Poor sleep quantity and quality
  • Shift work
  • Increased age

So how do these seemingly different mechanisms cause the same problem? Well, it turns out that insulin has a starring role in immune function. Specifically, it seems to direct the immune system based on a recent study.

“We have identified one of metabolism’s most popular hormones, specifically the insulin signaling pathway, as a novel ‘co-stimulatory’ driver of immune system function.”

Study co-author Dr. Daniel Winer

This makes perfect sense from a circadian perspective. Light entrains the master clock in the brain, but the feeding/fasting cycle entrains the peripheral clocks. And the immune system would fall under that second category.

In order to prepare the body appropriately, circadian rhythms create anticipation of the environment by these cues. For the peripheral clocks, insulin and IGF-1 are the primary hormonal cues to set the anticipatory rhythms.

Though insulin is high in Type 2 diabetes and low in Type 1, both impair insulin signaling. So, in essence, impaired viral immunity due to improper insulin signaling is circadian disruption. As a result, latent viruses can replicate, causing reactivation.

Reversing circadian disruption in chronic fatigue syndrome

To be fair, it takes a little more than circadian disruption to cause viral reactivation. A recent study in mice illustrates this nicely.

In the study, mice were exposed to murine gammaherpesvirus, a virus in the same family as EBV. Once the virus entered latency, the mice were exposed to either a normal light:dark cycle or circadian disruption resembling shift work. During initial virus exposure, circadian disruption had no effect on the virus.

Once the virus entered latency, mice were exposed to lipopolysaccharide and one of the 2 conditions. The combination of LPS and circadian disruption dramatically increased the viral load. Neither LPS alone nor circadian disruption had a significant effect on viral load.

It’s important to point out we have tons of LPS in our gut that enters the bloodstream during leaky gut. Thus, this study implies a 2-hit model where viral immunity is compromised when mice are exposed to both leaky gut and circadian disruption. This combo may lead to reactivation of latent viral infections.

In addition to setting the immune clock, proper insulin signaling also helps set the peripheral clock in the gut. Thus, impaired insulin signaling provides both hits of the 2-hit model that can lead to reactivation of viral infections.

Type 2 diabetes is the classic presentation of chronic insulin resistance. But one need not have it to experience acute insulin resistance. Anyone can induce insulin resistance and many people likely do it regularly.

Jet lag, social jet lag, inactivity, high calorie intake, and all of the contributors to Type 2 diabetes mentioned above cause transient insulin resistance. I don’t think one needs to have Type 2 diabetes for viral reactivation, a simple long bout of acute insulin resistance at the wrong time will do the trick. At least, based on this mouse model.


Reactivation of latent viral infections is considered a cause of chronic fatigue syndrome. Recent studies implicate circadian disruption as a cause of depressed viral immunity that can predispose people to CFS. This in combination with leaky gut causes reactivation of a latent virus in mice.

Correcting these issues is central to reversing chronic fatigue caused by viral reactivation. This allows the immune system to put the viral infection back in to remission. I have covered this in 3 testimonials you can find here, here, and here.

From there it’s about building resilience with lifestyle factors that prevent this 2-hit model from occurring. Ways to address this include:

  • Losing weight if you are overweight or obese
  • Decreasing calorie intake
  • Increasing physical activity
  • Building good circadian habits

Generally speaking, I think it’s relatively common for people to observe behaviors that promote both leaky gut and circadian disruption. I’m certain many people, including myself, will engage in these behaviors over the next 2 months. By taking the proper precautions, you can keep latent viral infections latent.

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