The amazing and powerful ways your gut keeps you healthy

There are many aspects of the gut that help prevent infection by microbes.  I’ve spent a lot of time covering bile and its antimicrobial effects.  Now it’s time to look at some of the physical properties in the gut.

The epithelial cells that form the wall of the gut function to keep unwanted particles out.  This is a simplistic view because bacteria and their metabolic products can cause significant damage if they come in to contact with epithelial cells.  They don’t need to cross the gut to cause damage.

 

Image result for villi gut

As you can see, the intestinal barrier isn’t a flat surface.  Epithelial and other specialized cells form finger-like projections called villi.  These vill increase the surface area in the gut for greater nutrient absorption.

Villi also serve a purpose in microbial defense and regulating the microbiome.  The finger-like villi are made up of different types of specialized cells.  These cells perform tasks that form a force-field like barrier from microbes.

Image result for mucus villi antimicrobial

The mucus layer use many methods for keeping bacteria away from epithelial cells.  If bacteria come in to contact with epithelial cells, the immune system initiates the inflammatory response to do away with them.  The composition of the mucus layer and the methods it employs to block bacteria differ depending on where you are.

In the stomach and colon, there are actually 2 prominent layers of mucus.  The first layer is attached to epithelial cells and densely packed.  This layer is so dense and viscous that most molecules can’t penetrate it.

The second layer is more loosely packed and ideally inhabited by good bacteria.  It’s not attached to epithelial cells and is loosely packed due to action by proteases.

The first mucus layer in the small intestine is basically non-existent while the loosely packed mucus layer is abundant.  Since the bulk of nutrient absorption occurs in the small intestine, having a dense mucus layer would block nutrient absorption.

Image result for small intestine mucus layer

Now that we have the basics of what the mucus layer looks like in these 3 areas, let’s take a look at the methods each area uses to maintain a healthy gut.

Defense in the stomach

Bacteria in the stomach are somewhat scarce due to the acidic pH.  The dual layer of mucus in the stomach functions more to protect our cells from acid damage than bacterial invasion.

The more densely packed inner layer is packed tight because the proteins that make up mucus are produced rapidly and folded.  These proteins, called mucins, become stacked and are resistant to enzymes that break mucus down.

In the stomach, parietal cells secrete gastric acid(H+) in to the lumen when you eat.  Mucous cells that produce mucins also produce bicarbonate(HCO3).  Bicarbonate is secreted in to the inner mucus layer and forms a chemical barrier that increases pH and prevents acid from damaging the cells in your stomach.

Image result for bicarbonate stomach

Notice how carbon dioxide(CO2) and water(H2O) are formed in the reaction between H+ and HCO3.  This is what contributes to the gas you expel when you burp.

As I mentioned, we don’t see too many issues with bacteria in the stomach due to the acidic pH.  The one you may be familiar with, Helicobacter pylori(H. Pylori), is often blamed for ulcers.

The vast majority of people in the world, including you, have H. pylori in their stomach.  It is normally harmless and only becomes problematic when it overgrows.  When this happens, pH regulation goes out of whack.

Truth be told, the association with H. pylori and ulcers is indirect.  H. pylori secretes enzymes that break down bicarbonate.  When this happens, the inner layer doesn’t contain enough bicarbonate.  Stomach acid isn’t neutralized and this damages cells leading to ulcers.  H. pylori isn’t damaging your stomach, it’s just making it possible for your own stomach acid to the job for it.

Using proton pump inhibitors(PPIs) works to manage these symptoms since less acid needs to be neutralized.  This does nothing to reduce the amount of H. pylori in the stomach and causes more damage due to poor nutrient absorption.  Ironically, reducing stomach acid via PPIs can make this worse if cells in the stomach don’t get the nutrients they need to form a densely packed inner layer.

Defense in the small intestine

The inner mucus layer functions as a barrier to most molecules.  It serves its intended purpose in the stomach and colon but would be detrimental to nutrient absorption in the small intestine.  The small intestine must use other methods to prevent bacteria from contacting the epithelium.

One such method involves the secretion of antimicrobial peptides(AMPs).  The villus structure of the small intestine is uniquely designed to prevent bacteria from inhabiting the crypts where cells that create AMPs reside.

Image result for paneth cells

At the base of the crypts we find Paneth cells that secrete AMPs.  A little further up, goblet cells secrete mucus that forms the mucus layer.  The AMPs mix with the mucus to form a chemical antimicrobial barrier.  This bypasses the need for a dense inner layer that would obstruct nutrient absorption.

Another method used to control bacteria in the small intestine is the oxygen gradient.  Higher oxygen levels down in the crypts prevent anaerobic bacteria from populating the area.  This is great since many commensals, including Lactobacilli and Bifidobacteria, are anaerobic.  Higher oxygen levels in the crypts and lower oxygen levels at the tips of villi make commensals keep their distance.  This prevents overgrowth in both the small and large intestine.

Image result for small intestine oxygen gradient

Having commensal bacteria also provides a level of protection against pathogens.  Even at a distance and in small numbers, commensal bacteria compete with pathogens for resources and regulate anti-inflammatory gene expression.  This prevents infection and damage due to the inflammatory process.

A final method of protection from bacterial infection involves the enzyme intestinal alkaline phosphatase(IAP).  Secreted at the brush border throughout the small intestine, IAP performs a couple of important tasks that reduces damage to epithelial cells in the gut.

Image result for intestinal alkaline phosphatase

First and foremost, IAP decreases inflammation by changing a component of the cell wall of pathogenic and commensal bacteria called lipopolysaccharide(LPS).  LPS is an extremely inflammatory molecule and there’s tons of it in the gut.  When LPS comes in contact with IAP, it gets changed in a way that renders it inert(1).

IAP also regulates pH(2) and ATP levels at the brush border(3).  This promotes the growth of commensal bacteria and deters pathogens(4).  IAP has been shown to be particularly effective at preventing antibiotic associated dysbiosis in mice(5).

All these factors work in concert to promote a healthy small intestine.  The presence of bacteria or chronic inflammation can throw the healthy small intestine out of whack.

Under normal operating conditions, there’s little bacteria in the small intestine.  You can thank the AMPs secreted by Paneth cells for that.  But, if bacteria are able to invade the mucus layer and enter the crypts they can destroy Paneth cells and this effect is lost.  Chronic inflammation has the same effect.

The problem doesn’t stop at Paneth cells.  Stem cells that lead to the production of other specialized cells begin in the crypts.  If these cells get destroyed many of the defensive functions in the small intestine are lost.  This reduces mucus production and alters the way the immune system responds to bacteria.

The oxygen gradient is effective in preventing overgrowth of commensals but not effective against bacteria that can survive in aerobic environments.  Many pathogens fit this description so another back up method is useful here.

Intestinal alkaline phosphatase(IAP) has gained prominence as a major contributor to mucosal defense.  It promotes an environment beneficial to commensals while keeping them out of places they shouldn’t be.  It does this by regulating pH, ATP, and inflammation.

Defense in the colon

The colon contains, by far, the greatest total amount of bacteria and the greatest number of bacterial species.

Image result for bacteria gi tract

Due to the greater number of bacteria in the colon, greater protection is necessary.  Some of these protective factors come from the bacteria that live there.

Bacteria use their own methods to beat competitors who may be looking for the same resources.  They do this by secreting their own antimicrobial peptides as well as antibiotics that kill competitors(6).  Penicillin was discovered by this mechanism.

Products of microbial fermentation such as short-chain fatty acids(SCFAs) also take part in regulating a healthy colonic environment by reducing inflammation.  More bacteria in the colon means a greater contribution from SCFAs than the stomach or small intestine.  Of course, commensals that produce SCFAs are what we want, not pathogens.

The colon also employs the same methods to control bacteria as the small intestine.  Since there is little nutrient absorption in the colon, a densely packed and attached inner mucus layer is appropriate.

Image result for colon dense inner mucus layer bacteria

The dense inner mucus layer prevents bacteria from adhering to epithelial cells(7).  It also prevents them from getting close enough to fire up the immune system.  This coupled with the help of the other methods of microbial defense do a great job of preventing damage to cells in the colon.

 Conclusion

There are many methods that the gut uses to maintain a healthy environment.  These methods:

  • Fight off pathogens
  • Regulate the amount of bacteria in the gut
  • Make sure commensal bacteria don’t overgrow where they shouldn’t

In order for the wrong type of bacteria to grow, they need to circumvent these defense mechanisms.  The same can be said for commensal bacteria growing in the wrong place.  This is one of the areas where I diverge from the current “starve them” or “blow them up with antibiotics or herbal antimicrobials” approach to GI problems.

To form a healthy microbiota, you need to make sure all defense mechanisms are in place.  I don’t doubt that antibiotics/antimicrobials can be useful, I just wonder how you plan to prevent relapse without restoring microbial defense.

Many common intestinal disorders including SIBO, IBS, and IBD are thought to have an initiating infectious event.  This event may compromise microbial defense and throw microbial balance out of whack.  This event may also be the manifestation of one or all these microbial defense components becoming defective.

In SIBO, bacteria grow where they shouldn’t.  In IBD, inflammation becomes chronic as one of these regulatory processes is defective.  Unfortunately, IBS is a more difficult nut to crack but SIBO seems to be involved.

Doesn’t it make sense to solve the problem by determining the cause?  I don’t think too many FODMAPS and an herbal antimicrobial deficiency quite qualify as the cause to most GI problems.

What did you think?  Want more stuff like this?  Does this resonate with you?  Drop some comments below and we’ll talk.

Image result for linda richman discuss

 

4 thoughts on “The amazing and powerful ways your gut keeps you healthy

    • cincodm says:

      Not altogether sure, but you could have been re-establishing better pH regulation. Are you familiar with the migrating motor complex? During periods between digestion you get a little dump of gastric acid and duodenal enzymes and that is propelled through the gut. If there was something blocking bicarbonate before and that something was knocked loose, you would definitely get a good amount of burping. Can’t say for sure but that could be the case. H. Pylori does this in the stomach. You could also have been swallowing more air when you drank if you were drinking more.

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