Do you have adrenal fatigue and/or a digestive disorder?  Do you feel like you may have cracked the nut and found a path not paved with daily sprints to the bathroom and constant low energy?

Is it disappointing that this path seems to be paved with a restrictive diet?  Low FODMAP, GAPS, or SCD got you missing the olden days?

Can’t eat this, can’t eat that.  Want a beer but can’t have one?  Would you kill for a slice of pizza?  It wasn’t always this way, why is an uber-restrictive diet now your life?  How can you go for decades eating what you want and then BAM!!!…No more?

I don’t think you need to eat a highly restrictive diet for the rest of your life.  Do I know for sure?  Hell no.  What I do know is that if you spent the vast majority of your life eating FODMAPs and now you can’t; that’s not a cure that’s symptom management.

Time to change your approach.  But first, lets take a look at some cutting edge research that hints at a base diet that’s not on your radar.

The inflammasome: Linking the adrenals to the gut

Before we delve in to the research, I just want to make one thing clear.  I don’t believe in the entity called adrenal fatigue. I know, sacrilege, right?

Instead, I believe that there is some large scale problem throwing every system in your body out of whack.  The adrenals, the gut, the thyroid, the immune system, everything.

In some people this may present more like classic adrenal fatigue.  In some people it may present more as hypothyroid.  In others, digestive disorders may be the major problem.  What do all these issues have in common?  The inflammasome.

Inflammasomes are signaling pathways that detect microorganisms and stressors and start inflammatory cascades to deal with them.  There are many different inflammasomes, but the one we’re going to stick with is mostly expressed in the gut.

The NLRP6 inflammasome regulates gut homeostasis.  In most instances, triggering an inflammasome causes inflammation.  But in the gut it actually reduces it.

Many recent papers help describe how this works.  Mice bred to not have NLRP6 have a much larger inflammatory response to colitis than normal mice(1).  When these mice are housed with normal mice, this effect is transferred to the healthy mice.  This implies that this effect is via the microbiome.

NLRP6 inflammasome and the microbiome

NLRP6 regulates the microbiome in at least 3 important ways.  First, there is direct interaction between the microbiome and inflammasome via bacterial metabolites.  Commensal bacteria generate beneficial signals that promote a healthy gut by activating the inflammasome.  In turn, the healthy gut promotes an environment beneficial to commensals(2, 3).

This works both ways as pathogenic bacteria create metabolites that block the inflammasome.  This generates an unhealthy environment and causes proliferation of an unhealthy microbiome(2, 3).  Some of these signals are also signals that our gut uses to initiate inflammation.  More on that in a bit.

The inflammasome is also responsible for secretion of antimicrobial peptides in the gut.  Inactivation of the inflammasome through gene deletion or bacterial dysbiosis in mice causes the loss of antimicrobial peptide secretion.  This, in turn, reinforces the dysbiosis and promotes colitis (2, 3, 4).

The other way the inflammasome regulates the microbiome is via mucus secretion by goblet cells(5).  Mice with NLRP6 deleted did not form an attached dense inner mucus layer in the colon.  This increased susceptibility to and prevented clearance of Citrobacter rodentium infections.

All these processes indicate that activation of the NLRP6 inflammasome is required to promote a healthy gut.  Additionally, NLRP6 is involved in intestinal repair.  Mice deficient in NLRP6 experience more damage from colitis due to impaired healing(6).  This coupled with the unhealthy environment promote an environment that promotes damage and dysbiosis.

Adrenal fatigue and the inflammasome

One of the hallmarks of adrenal fatigue is lower cortisol levels coupled with higher corticotropin-releasing hormone(CRH) levels.  When you experience stress, you trigger something called the hypothalamus-pituitary-adrenal axis(HPA axis).

Through the HPA axis, the hypothalamus secretes CRH which tells the pituitary gland to secrete adrenocorticotropin hormone(ACTH).  ACTH travels to the adrenal glands and causes them to release cortisol.  Cortisol then makes it back to the hypothalamus to shut off CRH release.

The finding that people with adrenal fatigue have higher CRH and lower cortisol levels led people to believe the cause was low nutrient availability to make cortisol.  In other words, people with adrenal fatigue need more of the nutrients that cortisol is made of.  It goes deeper than that.  It’s not poor nutrient status, it’s poor signaling.

During chronic inflammation, signaling of the HPA axis gets thrown off.  Cortisol production drops, but it isn’t due to poor nutrient status.  Cortisol production drops because inflammation causes defective production.

The generation of cortisol occurs in the mitochondria and endoplasmic reticulum(ER) in cells.  Chronic inflammation leads to mitochondrial dysfunction(7) and ER stress(8) that disrupt this process.  Making this problem worse:  Mitochondrial dysfunction and ER stress increase inflammation leading to a vicious cycle.

This brings about an interesting relationship between adrenal fatigue and gut disorders. This relationship centers around the inflammasome.  Elevated CRH suppresses the NLRP6 inflammasome in the gut.  This suppression promotes dysbiosis leading to increased inflammation.

In a recent study, mice were exposed to a chronic stress and monitored.  These mice experienced gut dysbiosis that led to colitis(9).  When these mice were housed with healthy mice, the dysbiosis was transmitted to the healthy mice who later developed colitis.

Don’t let this concern you.  You won’t catch adrenal fatigue from your friend.  Mice eat each others doodie and I assume you don’t eat your friend’s.

These findings support the idea that adrenal dysfunction and gut disorders perpetuate one another.  No matter which is the initiating event, defective inflammasome signaling leads to increased inflammation, microbial dysbiosis, and poor adrenal function.  Since these problems feed one another, the aberrant signaling needs to be addressed to fix the issue.

Searching for the fix

Recall earlier that I mentioned there are microbial signals that help regulate the inflammasome.  Identifying these signals should reset the gut and help re-balance both the gut and adrenals.

There are positive regulators of the NLRP6 inflammasome that activate it and negative regulators that suppress it.  Both can be manipulated.

Something that may blow you away is that both are diet related.  The positive regulator can be addressed with supplementation and the negative regulator can be addressed through diet.  What’s totally mindblowing is that there is already a base diet out there with tons of recipes that no one is using.  This diet isn’t GAPS, SCD or low FODMAP.

I don’t believe this diet needs to be a permanent change.  In theory, it shouldn’t take anywhere near as long as people get stuck on these other diets.  Antibiotics may even help get the ball rolling and speed up the process.  And you can take other precautions to prevent antibiotic induced dysbiosis.

What’s that I smell?  A private blog to group members detailing this?  You betcha.  Stay tuned and feel free to join here.  Any questions?  Pop ’em down in the comments section and we’ll discuss.