Keys to a healthy gut microbiome

A healthy gut microbiome may be key to living a long, healthy life. A recent review covered what we know to date, and another paper identified the microbiome as an effective clock to measure aging.

While not as accurate as the epigenetic clocks, it still had reasonable accuracy. Using deep learning, they were able to predict chronological age with fecal microbiome samples within 5.91 years.

Unfortunately, the relationship between the gut microbiome and different health outcomes has driven people to the mistaken conclusion that taking probiotics may cure things like Type 2 diabetes or fatty liver. This is wrong on multiple levels.

First, just because a microbe enters your mouth doesn’t mean it’s going to colonize your gut. Furthermore, if they don’t colonize, they likely won’t make the beneficial proteins that drive better health.

Finally, and most importantly, the health of your gut plays the dominant role in shaping your microbiome. While they certainly share a bi-directional relationship with one another, if you don’t take care of your gut, no amount of probiotics will make it healthy.

That’s because environmental conditions in the gut select for the microbes that reside there. You can take as many probiotics as you want, but if your gut function is compromised, your microbiome will be as well.

That is to say, if you want a healthy gut microbiome, you have to have a healthy gut. But which factors in a healthy gut promote a healthy microbiome? Let’s dig in…

Features of the gut that promote a healthy gut microbiome

One of the most helpful things to do when thinking about the microbiome is to think of the gut and it’s commensal inhabitants as a mini ecosystem. For example, think of the differences between ecosystems in dramatically different climates.

If we go to Antarctica, it’s cold, dry, and nasty. As a result, few plants grow there and they only grow during very limited times. Consequently, not a whole lot of herbivores live there either.

But now let’s look at the Amazon rainforest. The wet, sunny, tropical climate has this ecosystem teeming with plant and animal life year round. In fact, 10% of the World’s species are found there. You’ll find plants, insects, herbivores, carnivores, and omnivores.

But if you take a monkey out of the rain forest and drop it into Antarctica, you can’t really expect it to thrive. So why would a probiotic dropped in to an unhealthy gut expect to do the same?

Ultimately, healthy conditions in the gut promote a healthy microbiome. So which factors promote a healthy gut, and thus, a healthy gut microbiome?

Motility for a healthy gut microbiome

Gut motility

Proper gut motility acts very much like flowing water. Faster motility inhibits bacterial growth. In contrast, stagnation promotes bacterial growth

This is why bacterial numbers are dramatically lower in the smaller intestine than the large intestine. Despite being much longer, food moves through the small intestine in about 6 hours. In the colon, it can sit for 24-48 hours.

It’s interesting to point out that gut motility is regulated through a bi-directional relationship between the gut microbiome and enteric nervous system, which is further regulated by feeding behaviors and circadian rhythms.

Mucus secretion

Goblet cells in our intestinal lining, also called the epithelium, constantly secrete a gel-like mucus. Much like gut motility pushes bacteria along the GI tract from the mouth to the colon, mucus pushes bacteria away from the epithelium and more towards the lumen(The center of the tube). It also traps bacteria and allows motility to send them packing.

Additionally, the mucus layer in the small intestine is different than in the stomach and large intestine. In the small intestine, the mucus is only a single layer, not adhered to the intestinal epithelium, and less dense. This owes to the absorptive function of the small intestine.

However, the mucus layer in the large intestine is composed of 2 layers. The inner layer is attached to the epithelium and denser than the outer layer. This keeps bacteria away from the epithelium, which is why few bacteria reside there.

In contrast, the outer layer is not attached and more porous. Interestingly, the outer layer is actually the remnants of the inner layer, after bacteria that can break it down have done so.

As such, the outer mucus layer in the colon is where most of the microbiome hangs out. Under ideal conditions, they can’t penetrate the dense inner mucus layer. In addition to fermenting the mucus layer, some bacteria can adhere to it, come into close contact with the intestinal epithelium, and stimulate secretion of mucus.

Antimicrobial peptides and digestive enzymes

In addition to keeping things moving, it’s also a good idea to have chemical mechanisms for suppressing pathogenic bacteria. Enter digestive enzymes, bile and antimicrobial peptides.

Digestive enzymes such as gastric acid from the stomach, proteases and lipases from the pancreas, and bile acids from the gallbladder have antimicrobial properties. Interestingly, many types of beneficial bacteria are resistant to some of these.

For example, gastric acid in the stomach kills much of the bacteria that enters it. Though, some species of bacteria can survive the acidic conditions of the stomach, including many beneficial ones.

Additionally, while bile acids act sort of like a soap in the small intestine, certain strains of Lactobacillus and Bifidobacteria are bile resistant. In addition, they convert bile acids into secondary bile acids that alter the microbiome and our metabolism.

Paneth cells, which are located in the crypts of the epithelium, secrete antimicrobial peptides(AMPs) such as REG3g &b, a-defensins, IgA, and lysozyme. These AMPs seed the mucus layer, giving it both chemical and mechanical methods for inhibiting pathogenic bacteria.

Microanatomy and a healthy gut microbiome

Finally, the microanatomy of the gut also serves to limit areas where bacteria reside. The attached inner mucus layer keeps bacteria out of the crypts. In the small intestine, fingertip projections called villi not only increase the absorptive area, they also prevent bacteria from entering the crypts.

The crypts contain intestinal stem cells(ISCs) and paneth cells necessary to regenerate intestinal cells. The microanatomy, mucus layer, and AMPs prevent bacteria from interfering with this process. Inflammation shortens the villi and impairs the regenerative capacity of the ISCs.

Unfortunately, this create other problems as well. The villi also contain mucus secreting goblet cells, so damaging the villi also reduces the mucus layer. Enteroendocrine cells are also in the villi, and these cells are essential for the function of the enteric nervous system.

The enteric nervous system is the resident nervous system in the gut. It regulates all of the factors mentioned above, including motility and mucus, AMP, digestive enzymes, and bile secretion.


Building a healthy gut microbiome is contingent on building gut health, much like a cleaner, nicer building attracts better tenants that will take care of the place.

The gut has several important mechanisms for attracting the right inhabitants. This includes the microanatomy of the epithelium, proper motility, mucus secretion, antimicrobial peptides, digetsive enzymes, and bile.

And while ensuring these functions are intact promotes a healthy microbiome, the microbiome actually plays a role in regulating some of these functions. Thus, it’s a bi-directional relationship.

This is why it’s not crazy to think that probiotics may be useful. However, it also indicates why probiotics on their own are insufficient. Thus, to ensure your efforts do not go to waste, it’s important to make sure that all these measures are in place to help select for a healthy microbiome.

We’ll dig in to each of these factors as well as things we can do to improve them in a future blog series.

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