New study provides key factor to avoiding leaky gut?

Over the last few years, “leaky gut” has moved from pure quackery to one of the leading topics in immunological research.  Part of this is because people refer to it as leaky gut, which doesn’t really lend any scientific credence to the topic.  Truth be told, I hate this term, preferring the much more scientifically accurate intestinal permeability.  But I can’t control what people search over the internet.

As you may have guessed by the name of my blog, I feel gut health is a critical factor in overall health.  But my perspective is vastly different than most on the subject.  In a time when people focus solely on things like probiotics, antimicrobial supplements, glutamine, and other things that we put in to our gut, my approach is firmly planted in lifestyle that includes multiple factors.  Things like circadian rhythms and such.

In my opinion, the study last year showing the microbiome of healthy older people being similar to the microbiome of healthy younger people simply underscores how important lifestyle is to maintain a healthy microbiome AND make it in to your 80s and 90s.  You just don’t see obese 90 year olds walking around.  You can throw genetics in there too, obviously.

Further support for this idea comes from a new study I believe will become a game-changer for some people.  In this study, researchers wanted to determine if inducing high blood glucose(Hyperglycemia) in mice had any effect on leaky gut, aka intestinal permeability.  They found quite a bit…

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Hyperglycemia and leaky gut

It’s part and parcel of gut health protocol to avoid sugar.  The story goes you want to avoid sugar because it will feed bad bacteria which will overgrow, cause leaky gut, and make your life a living hell.  And let’s not forget the chronic inflammation this effect induces.

This theory falls through on one very important point: Sugar won’t typically make it to the colon where most of our gut bacteria reside because we absorb it very well.  Sure, you could probably eat enough sugar to the point you don’t absorb it all, but that would be a huge amount of sugar.  Then the question becomes is the problem the sugar or the ginormous amount of calories you’re consuming?

However, there’s another mechanism by which excess sugar consumption can increase leaky gut: By increasing blood glucose to the point of hyperglycemia and/or hyperinsulinemia.  And that’s just what these researchers decided to decipher.

In the study, researchers took mice and induced hyperglycemia.  I won’t bore you with the details of how this worked, but what they found was very interesting.  First, inducing hyperglycemia reliably caused leaky gut and systemic disbursal of bacteria from the gut in to the blood and organs of mice.  And it was the increase in blood glucose that caused it, neither insulin nor the appetite hormone leptin had any effect on their own.

Furthermore, hyperglycemia reprogrammed the way the epithelial cells lining the gut worked by changing the expression of more than 1000 genes.  They also found a reprogramming of immune cells in the gut and spleen towards myeloid cells, something I discussed as being a telltale sign of “inflammaging” and promoter of aging-related disease in my last blog.

To find out if this was from a change in the microbiome, they took a look at the microbiome to see what was doing.  While they found changes in the microbiome of mice with hyperglycemia, transplanting their microbiome into healthy mice didn’t cause leaky gut.  They ultimately found that altered glucose metabolism in the cells that make up the gut wall caused by hyperglycemia was the culprit.

While your first response to this may be that mice aren’t humans, the study doesn’t end here.  To determine if this holds true in humans, the researchers recruited 27 healthy human volunteers to see if there is any measure that can reliably predict the amount of microbial products in the blood.

Of the measures, HbA1c most reliably predicted the amount of bacterial components in the blood of humans.  It’s important to note that HbA1c functions as a 3 month average of your blood glucose.

Circadian rhythms, hyperglycemia, & leaky gut

These findings give us some very clear insights in to the damaging effects of hyperglycemia on the gut.  Not only does it appear to cause leaky gut, it appears to reprogram both the gut and systemic circulation in to pro-inflammatory environments.

Thus, reducing sugar in the diet isn’t a good target, maintaining healthy blood glucose levels is.  Fortunately, anybody in the US can go to CVS and purchase a pair of HbA1c tests for $40 and determine if they have adequate blood glucose control.

That’s the good news, now for the bad news.  This appears to be a self-perpetuating problem.  One thing the researchers found was that insulin blocked the leaky gut inducing effects of hyperglycemia.

Insulin, and thus blood glucose, follows a circadian rhythm and inducing mild chronic hyperglycemia and/or hyperinsulinemia in healthy individuals messes with your circadian system by disturbing your autonomic nervous system.  Within 48 hours, the circadian variation of heart rate and blood pressure are lost due to reduced activity of the vagus nerve.

While we know poor sleep begets poor blood glucose control, it appears that poor blood glucose control may also beget poor sleep.  But rather than being a “Circadian disruption causes hyperglycemia” situation, it’s more like sleep-deprivation alters the circadian rhythm of blood glucose regulation leading to lower levels during sleep and first thing in the morning, but higher levels during the day…You know, when you eat.  Probably not a great time to be experiencing hyperglycemia-induced leaky gut.

Even though insulin and blood glucose follow a natural circadian rhythm, many lifestyle factors such as meal content, meal timing, diet composition, light exposure, physical activity, and sleep can all adjust the circadian rhythm of both insulin and blood glucose.  Keeping both in an optimal range all comes down to layering the above factors appropriately throughout the day, something I’ve discussed before.


The focus on avoiding sugar consumption to prevent leaky gut appears to be misguided.  Based on recent evidence, a better target is to maintain good blood glucose control, which isn’t necessarily accomplished by avoiding sugar.  The best way to accomplish proper blood glucose control is through a multilayered approach addressing lifestyle.

Addressing factors such as physical activity, light exposure, sleep quality and quantity, meal content and timing, and how you layer these things throughout the day will provide far better control over your blood glucose than avoiding sugar.  Using HbA1c as a way to measure your progress allows you to determine if you’re doing things properly.

Evidence is piling up that paying attention to your circadian rhythms may be the most critical factor to living a long, healthy life.  It certainly makes sense, the entire point in having a circadian rhythm is to adjust your physiology to the environment to optimize success.  In the past, this allowed us to better find food and survive long enough to pass on our genes to our offspring.  Now, it just may be the key to avoiding chronic disease, including those with origins in the gut.


8 thoughts on “New study provides key factor to avoiding leaky gut?

  1. Susie says:

    My first thought was this is really bad news for new moms that generally lack good sleep for around a year (sooner if your lucky)! And wouldn’t that in turn affect breast milk quality? I’ve often wondered why my breastfed babies have food sensitivities and other formula fed babes have no issues. I know there’s a lot more to it…

    • cincodm says:

      There’s definitely more to it and you’d think that would be factored in there from an evolutionary standpoint. Reasons for food sensitivities can range from birthing method, microbial exposure, antibiotics, how early they’re exposed to a food, etc.

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