Fixing leaky gut: What you need to know!

Fixing leaky gut is no straight-forward problem. It’s not like you have a hole in your tire that you simply need to patch. It’s more like you have a hole in the bottom of your boat and you’re 5 miles offshore. Consequently, you’re screwed.

Your gut isn’t just a tube that gets holes in it. It’s a biological barrier that selectively lets good things in and keeps bad things out. That is to say it’s a dynamic interface, not simply a border.

It’s perfectly normal for you to have leaky gut. In fact, it’s physiologically necessary. But when it fails at the wrong time, bad things happen.

A new study in mice gives us a clue as to how permeability of the small intestine works under normal conditions. Even better, there’s a cool infographic to go along with it that makes it easier to understand.

Let’s break it down.

Fixing leaky gut in the small intestine

Fixing leaky gut: Regulation of small intestinal permeability

A lot of important factors go in to the regulation of the small intestine. Our physiology was built on an engine that evolved in nature, something we take for granted. As a result, modern society has a way of physically breaking us down.

It does this by divorcing us from an environment that regulates our circadian rhythms, those of our microbes, and synchronization of both.

Tile 1-Host circadian rhythms

In a general sense, it all starts with host circadian rhythms, depicted in tile 1 of the infographic. Proper exposure to light and variations in core body temperature play the dominant role in our circadian rhythms. This causes us to go out searching for food at a species appropriate time. (Daytime for us, nighttime for mice)

This normally aligns with advantageous traits. We are a visual species with terrible night vision. Under normal conditions we attain our food during the day. This makes nutrient intake commonly during the daytime for us, nighttime for mice.

Disrupting our circadian rhythms by altering light exposure or activity patterns also disrupts the circadian rhythm of permeability in the small intestine. At the same time, it can also increase susceptibility of inflammation by impairing tolerance of the immune system.

Tile 2-Feeding the food entrainable oscillator

Our light exposure and activity patterns create variations of food intake that regulate a food entrainable oscillator. Consistent feeding patterns help synchronize peripheral circadian clocks. These clocks reside in every cell in every organ in our body.

It’s important to not only synchronize the clocks in different organs, it’s also important to synchronize the individual cells in a specific organ. Looking at the gut, this optimizes gut functions such as motility, digestion absorption, and maintenance of a strong intestinal barrier. Furthermore, this sequesters these functions to the appropriate time of day.

It also causes diurnal variations in the microbiome.

Tile 3-The microbial clock

When we think of the microbiome, we often think of the colon. This makes sense, more than 99% of the gut microbiome lives there. But just because there are fewer microbes in our small intestine doesn’t mean their job is any less important.

Our feeding rhythm causes variation in the types and numbers of bacteria in the small intestine. Consequently, this changes what goes on in our gut. As a result, our gut and microbiome team up to regulate functions in the small intestine.

Variations in different species in the gut regulate intestinal permeability. Some species increase intestinal permeability, while others strengthen the intestinal barrier.

Tiles 4, 5, & 6-How the microbiome regulates small intestine permeability

Synchronization of our circadian rhythm, the small intestine circadian rhythm, and the microbial circadian rhythm causes a diurnal fluctuation of small intestinal permeability. Bacteria that strengthen the barrier bind to the epithelial cells that make up the lining of the small intestine.

This increases expression of a protein called myosin heavy chain II(MHCII), which increases the presence of immune cells in the small intestine. These immune cells (CD4+ IL10+ IELs) secrete an anti-inflammatory cytokine (IL10), that regulates intestinal permeability and prevents excessive inflammation.

This causes variation of intestinal permeability where permeability is higher during the active period, but at the same time, tolerance is promoted. This means that even though permeability of the intestine is higher during our active/feeding period, immune cells in the gut put the brakes on inflammation.

Moreover, during the resting/fasting period, permeability of the small intestine is lower, but we are more susceptible to inflammation.

Fixing leaky gut

Based on this intricate system, fixing leaky gut in the small intestine isn’t as simple as tossing some glutamine down our gullet or taking a probiotic supplement. Those can help, but they are just one small piece of a very large pie.

In this study the researchers found that a kink in any part of the 5-point chain in the infographic causes leaky gut. Furthermore, it will increase inflammation, which is obviously bad. Through different means they identified the following factors that can cause leaky gut in the small intestine:

  • Circadian disruption (They used jet lag and genetic models)
  • Altering feeding patterns (TRE shifted permeability rhythm)
  • Diet quality (Junk food diet eliminated the rhythm, even under TRE)
  • Dysbiosis (Antibiotics, junk food diet, and FMT altered permeability by changing the microbiome)

Furthermore, consistency in all of the above are critically important to establishing this strong rhythm.

For example, erratic eating or activity patterns causes misalignment between the permeability/immune tolerance rhythm and food intake. As a result, feeding causes inflammation and damage to the small intestine.


Our gut is often portrayed as simply a wall that keeps out foreign invaders. This picture is inaccurate. It’s actually a dynamic interface that is regulated by behavioral patterns that optimizes its function based on environmental factors.

In a way, it’s a wall that gets broken down every day and rebuilt by our microbial workers. Furthermore, these microbial workers also tell firefighter in our gut to put out the fires of inflammation during times the wall breaks down.

Fixing leaky gut, or even preventing it, depends on making sure this system functions properly. To do this, we must build a strong circadian rhythm through our patterns of light exposure, activity, and feeding patterns.

In addition, a healthy menu is critical to ensure that we attract the right workers for the job. all of these factors are essential for building a strong, healthy, resilient gut.

2 thoughts on “Fixing leaky gut: What you need to know!

  1. Ian says:

    Seems interesting and potentially plausible, but I wonder how much of this stuff actually applies to humans and not just mice

  2. cincodm says:

    Therein lies the difficulty. It appears circadian rhythms do essentially the same thing in us, but this isn’t something you can measure in a live human to confirm the precise mechanism. I suppose the only way to be sure is if the mechanism is shared among other mammals and thus may be conserved in us.

Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.