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How to Maintain a Healthy Microbiome

Understanding the Human Microbiome: Part 2

In part 1, we covered the basics of the human microbiome and how important a healthy microbiome is for a healthy body. In particular, we highlighted the key role of bacterial diversity in establishing that healthy microbiome.

Fortunately, you have a lot of influence over your microbiome, and you can promote a healthy microbiome through lifestyle choices, such as a healthy diet and exercise.

Here in part 2, we dive deeper into these good lifestyle choices and call out the things to avoid. We will also do some myth-busting about generic probiotics and their health claims. At the end, we close with a note about the exciting potential for leveraging engineered probiotics to enhance bodily functions without disrupting the resident microbiomes.

 

Good Practices to Use

Diversify Your Diet 

Different microbes in your gut need different nutrients to thrive. By increasing the variety of food you put in – particularly the variety of complex carbohydrates, dietary fibers, and resistant starches from plants (e.g. fruits, vegetables, grains, and legumes) – you are feeding as many species as possible, providing them with the energy necessary to reproduce and carry out metabolic activities. 

That’s why a diverse diet is crucial to improving gut microbiome diversity. 

Recalling our flea market analogy from the previous post, if you want to bring in a diverse variety of different customers (bacteria) to your flea market (your gut), you need to have lots of different kinds of stalls providing a variety of goods (diverse food/nutrients) to attract those customers and keep them coming back. If the vast majority of your stalls only offer rugs, for instance, you’ll start to only attract customers who want rugs. If your goal is to bring in lots of different kinds of customers (achieve microbial diversity), then you need to offer more than just rugs (eat more than just one kind of fiber/resistant starch). 

Sadly, 75% of the food in mainstream supermarkets is produced from only twelve plants and five animal species (citation). So, to some extent, the food system is stacked against us in our efforts to get diverse sources of fibers and resistant starches. However, with a little bit of effort to spend more time in that other 25%, we can make a lot of progress supporting a healthy and diverse microbiome.

 

Healthy, plant-based food, by photographer Maddi Bazzocco

Eat More Plants to Get More Dietary Fibers and Resistant Starches

The first step to diversifying the gut microbiome is to make sure nutrients are available to them. The key nutrients in this regard are dietary fibers and resistant starches, found primarily in plant-based foods.

In most plants, there are carbohydrate polymers that are neither absorbed nor digested by humans, and thus reach the colon (the end of the human GI tract) intact. Collectively called dietary fibers and resistant starches, these molecules are then utilized as a food source by the gut microbiota, stimulating their growth and metabolic activities. 

They are most commonly found in plant-based foods like fruits, vegetables, grains, cereals, legumes, seeds and nuts. And they are often referred to as “prebiotics,” since they are a necessary PREcursor to a healthy microBIOTA.

Not all dietary fibers and resistant starches are the same, though. They vary significantly in properties that affect how easily different microbes can access them, how completely microbes can digest them, and where in the GI tract they are digested. In addition, different plant-based foods contain drastically different compositions of these fibers and starches. That's why each food appeals to different members of your microbiota (citation). 

In other words, the key to a diverse diet is to introduce a large variety of dietary fibers and resistant starches that different microbes in your gut selectively consume. Indeed, cross-sectional studies confirmed the positive impact of plant-rich diets on microbiome diversity (citation, citation).

In order to help paint a picture of what we mean, we’ve put together a table with some examples of some different fibers and resistant starches, as well as the food sources they come from:

Sources of dietary fiber and resistant starch

 

(Citation)

This is by no means a comprehensive list, but you can start to see that eating a diversity of grains, vegetables, roots, nuts, seeds, and fruits will provide you with lots of different types of fiber and resistant starches. It is important to note that even within each column, the different food sources provide different kinds of each fiber. For instance, you will get a very different β-glucan from whole wheat than you will from a yeast cell wall. And even those differences are meaningful to fostering a diverse microbiome.

Take Prebiotic Supplements

For an extra nudge to feed your gut bacteria, you can use prebiotic supplements to accompany your plant-rich diet. 

When buying prebiotic supplements, don’t just think about the amount of dietary fiber you’re trying to consume. (the amount of daily fiber recommended by health experts: is 25 grams for an adult female and 38 for an adult male, while one typical dose of a prebiotic supplement contributes about 5 grams [citation, citation]). 

So it’s as much (or more) about the type of fiber than the amount. All prebiotics are not created equal. As discussed above, different dietary fibers and resistant starches (i.e. prebiotics) feed different microbes, and the needs of your microbiome will definitely be different than the needs of someone else’s microbiome. As such, just taking a generic “prebiotic” may or may not provide you with a benefit, depending on if it is a fiber/starch that your microbiome needs. 

As such, much like with a diverse diet, you may need to experiment with different prebiotics or even potentially try several to get a true benefit. 

QUICK NOTE ON THE BENEFITS OF PREBIOTIC SUPPLEMENTS

If you're thinking about prebiotic supplements, it's worth keeping this in mind: unless you experience the physical consequences of your microbiome's health (good or bad, e.g., satiation/hunger, healthy food cravings/bad food cravings, regularity/lack of regularity, mood effects, etc.) it's actually pretty difficult to know whether particular prebiotic supplements are providing that benefit or not. The best way to know would be to get routine microbiome sequencing, but that's not feasible for most of us. Not that this means don't take or experiment with them – just know that it might be tough to discern how it's going when you do.

Fortunately, prebiotic supplement labels include information about the specific prebiotics in the product. Some useful prebiotics commonly found in supplements include:

  • Fructans (e.g. inulin [often extracted from chicory root] and fructooligosaccharides [FOS])
  • Galacto-oligosaccharides (GOS)
  • Resistant starches (e.g. raw potato starch or green banana flour)

 

Woman exercising on beach, from Unsplash

Exercise

You are probably aware of the many perks of exercise, but if your gym membership card has long turned into a museum artifact, here is some extra motivation for you.

The effects of exercise on the microbiome have been explored in numerous studies over the last decade. In a cross-sectional study with rugby players, regular training led to greater overall diversity and increased richness of 40 species in the gut microbiome (citation). In contrast, longitudinal studies with sedentary (inactive) individuals showed that six weeks of supervised endurance exercise altered participants’ microbiomes in potentially beneficial ways, depending on their body mass index (citation).

Although not thoroughly tested, there are several theories about how exercise can improve gut microbiome diversity. To put it simply, the microbes in your body are not only affected by what you eat but also by the environment around them (i.e. your body). As it turns out, exercise can potentially bring these conditions to an optimal level for many bacteria to thrive. These conditions include but are not limited to the integrity of the gut mucus layer (where bacterial colonization takes place; citation), reduction of nutrient transit time (to make nutrients available to bacteria more quickly; citation), pH, and temperature.

While these mechanisms need further investigation, the growing body of studies makes us feel confident enough to encourage exercise for a healthy microbiome.

 

Bad Practices to Avoid

Unhealthy, sugary food, by photographer Maddi Bazzocco

High Sugar Diet

While some nutrients promote the growth of beneficial bacteria, as you can imagine, too much of certain nutrients could hinder that growth or promote too much growth of bad or minor bacteria. 

Exhibit A is sugar. When consumed in excessive amounts, sugar is one of the main antagonists of microbial diversity. 

Just one example of studies done on this subject was a study in mice that clearly demonstrated that eating a high sugar diet resulted in a decrease in the overall diversity in the mouse microbiome, as well as a shift in the microbiome consistent with higher levels of systemic inflammation and metabolic disorders (citation). The mice in the study developed gut inflammation, abnormal blood glucose levels, and fat accumulation. Interestingly, the mice remained within normal-weight limits, creating a situation referred to as “normal-weight obesity” (aka “skinny fat”).

This study shows us that high sugar intake does not have to manifest as weight gain to inflict harm. A high-sugar diet impairs the very function of your gut by changing the population of bacteria living inside of it.

High Fat / High Protein Diet

Similar to sugars, fat and protein – despite being essential for your health – can damage your microbiome when consumed excessively.

One study showed that a high-fat diet in mice was responsible for distributing the population ratio of different microbes known as the Bacteroidetes-to-Firmicutes ratio. That disturbance is affiliated with chronic gut inflammation, which leads metabolic diseases like insulin resistance and obesity (citation). 

Protein, too, can sometimes be too much of a good thing. While there is some data about the benefits of high protein diets for human health, its potential dangers should not be overlooked. 

Certain protein fermentation products produced by the microbiome (such as L-carnitine from red meat and amino-acid-derived compounds) have already been associated with impairments in the central nervous system and blood circulation, leading to CNS diseases, obesity, and type 2 diabetes (citation). 

In addition, what scientists commonly observed in several animal models given a high protein diet was a significant decrease in microbial diversity, particularly a reduction in short-chain fatty acid-producing bacteria, which are critical for gut health.

Alcohol

As we emphasize in many of our blog posts and on our website, alcohol and its byproduct acetaldehyde are the main actors behind the chaos that ensues in our bodies when we drink. Unfortunately, they also can have some undesirable effects on our microbiome as well.

In both humans and various animal models (citation, citation, citation), alcohol was shown to directly reduce microbial diversity. Furthermore, alcohol caused leakage of certain bacteria and their metabolites into the bloodstream, which resulted in liver damage (citation), and disruptions in the gut-brain axis. This caused changes in mood, cognition, and future drinking behavior (citation). 

Stated another way, alcohol can perturb the microbiome. This alteration in the microbiome can cause changes to the health of your body and your psyche, indicating how important a stable microbiome is to your overall health. Many of the things we associate with harm due to alcohol are actually at least in part mediated by the disruption that alcohol causes to our microbiome.

Stress

Your gut microbiome has undeniable power over your brain, but the same is true the other way around. In other words, your neural activity - for example, your stress response - can alter your microbiome.

A recent animal study from the Ohio State University College of Medicine constitutes an excellent demonstration of the stress-gut microbiome relationship (citation). When the researchers simultaneously exposed mice to social stress and the pathogenic bacteria Citrobacter rodentium, the stressed group exhibited significantly higher gut inflammation in response to the pathogenic bacteria than the undisturbed group. When they looked at the microbiome composition, they identified certain types of bacteria to be particularly important for protection against inflammation, and the induced stress had caused a decrease in these bacteria. 

This indicates that stress can shrink the good bacterial populations that protect against some pathogenic (harmful) bacteria, which gives these pathogens more room to grow and become active.

 

Unavoidable Disruptions to Look Out for

It might seem strange to squeeze in the following John Lennon quote amidst the fountain of scientific information, but here it is: “Life is what happens to you while you are busy making other plans.” 

Sometimes, you might face certain health matters – such as cancer or an infection – that force you to take certain therapies for a while. Most of the time, these therapies are not quite targeted (i.e. they kill healthy cells and beneficial bacteria as well), but they are necessary for survival.

Antibiotics are the number one inevitable disruptors of the microbiome. It’s been found that antibiotic use could reduce the abundance of 30% of the gut microbiome. More importantly, it can take months or even years for the microbiome to return to its original state (citation, citation).

Conventional chemotherapy could also result in severe disruptions in the microbiome. For example, one study of patients on chemotherapy showed a significant deleterious shift in the microbiome (citation), which accelerated pathogenic bacterial growth (e.g., E. coli) and increased the risk of gut infection.Perhaps the most severe implication of this shift is an increased rate of C. diff infection, something we discussed in the last section of part 1 of this blog piece. Higher C. diff infection rates have been reported following treatments with chemotherapy drugs like cisplatin and paclitaxel, among others.

However, while these changes are inevitable if you need to take certain medications, it is important to note that the benefits of these medications usually significantly outweigh their impact on your microbiome. So we identify these not as things to avoid, but instead as things to be aware of so that you can compensate for their effects by implementing a plant-rich diet and exercise with the guidance of your doctor.

 

Are Probiotic Supplements Helpful?

When reading about diet and gut health, you will come across the term “probiotics.” While “prebiotics” are nutrients that microbes metabolize, the word “probiotics” refers to the microbes themselves. You can obtain probiotics from food sources – often fermented foods such as yogurt, kefir, and kombucha – as well as probiotic supplements.

The probiotic supplement industry continues to grow, grossing over $40 billion per year. All of it falls under the broad definition of products that, when taken in adequate amounts, live organisms confer a health benefit to the host (citation). This definition is quite vague, and its breadth hides some significant drawbacks. In commercially available probiotics, we often see insufficient evidence of viability in the body, inadequate information about the species and strains being used, and consequences that include possible disruptive effects on the microbiome. We explain these problems in much greater detail in this article.

In short, the main problem is this: there is no consistent proof that probiotics promote a healthy microbiome. 

The reason for the lack of promising results actually lies in the phrase “healthy microbiome.” Remember how, in part one, we emphasized that every microbiome is different?

Each person’s microbiome is extremely individual, so the response to a given microbe in a probiotic is likewise very individualized. Put another way, some probiotics could help some people some of the time, but there are no silver bullets or reliable or predictable responses between people or even within a single individual at different times (citation). That’s why we cannot expect a specific strain to have the same effect (or really any effect at all) on everyone.

Going back to our flea market analogy, you could imagine a visitor who is a large purchaser of furniture (maybe they are an interior designer?!) being a very valuable and important customer at a flea market that has lots of furniture vendors, but being completely useless at a flea market that focuses more heavily on clothes, jewelry, and toys. The idea that you could have a “super-spender” that just comes into any market, regardless of what they are selling, and just buys willy-nilly (essentially the premise of a universally beneficial probiotic) is not particularly likely. 

In addition, some commercial probiotics may in fact do more harm than good, depending on the situation. 

Recent cutting edge in vivo human studies demonstrated that probiotics could delay the restoration of your microbiome after antibiotics use (citation). This shouldn’t be surprising: taking a microbiome recently disrupted by antibiotics and bombarding it with probiotic bacteria that are not even part of a normal adult microbiome (most commercially available probiotic strains are not commonly found in large percentages in an adult microbiome) should not be expected to be good for you! It is a weird and flawed hypothesis, and the data confirms what we all should have expected from a simple thought experiment. 

It is akin to bombing your lawn with weed killer and then sprinkling clover seeds everywhere, and then being surprised when your grass grows back more slowly because it has to compete with clovers now. Wouldn’t it make more sense to follow up that weed killer with fertilizer (i.e. prebiotics) that feeds the surviving grass to multiply again and re-cover your lawn? 

 

Engineered Probiotics

All that being said, genetic engineering has opened a lot of doors to make probiotics more beneficial. By leveraging the bacteria’s natural ability to edit their own DNA (as we discuss in more detail here), scientists can now generate probiotic strains with specific functions, and it is these functions (and not the bacteria itself) that makes the genetically engineered probiotic useful. Probiotics produced this way could easily target specific pathogens or serve predetermined functions without disrupting the composition of the gut microbiome (citation).

ZBiotics is an example of how engineered probiotics could be used to execute a beneficial function. The gastrointestinal tract lacks the aldehyde dehydrogenase enzyme to metabolize acetaldehyde, which accumulates in the gut after alcohol consumption, often causing unwanted effects that leave us miserable the next day. By genetically engineering probiotic bacteria to produce acetaldehyde dehydrogenase, we aim to improve the ability of the gut to metabolize acetaldehyde without disrupting the microbiota.

ZBiotics bottle

As stated in the previous section, it is unlikely that you’d get a “super-spender” that was just generally good for any and every flea market (which is essentially the current hypothesis behind probiotics). However, you could imagine a person who was trained to do a specific job really well whenever you needed it, such as sweeping up trash. You could drop this person off at any flea market, and if there was trash, they would sweep it up. If there wasn’t, then they’d just walk through the flea market and do nothing. Either way, if this person is present, then you can be sure there would be no trash on the ground, which is a good thing! Engineering probiotics is taking this same mentality, that a reliable function is what is important, rather than just something that is meant to be vaguely and non-specifically “good for you”.

 

Conclusion

We realize that we have given you a lot to digest. The main ideas we are trying to convey are that:

  1. Microbial diversity is critical to a healthy microbiome
  2. A diverse diet, rich in different kinds of fibers and resistant starches, supports that diversity, as do activities like exercise
  3. Too much sugar, excessively high fat or high protein diets, and stress can all reduce your microbial diversity and leave you susceptible to disease and inflammation
  4. Prebiotic supplements can potentially be helpful, but the hypothesis (and data) for the benefits of probiotics is not as strong
  5. Genetically engineered probiotics are the next frontier, reliably providing useful and specific functions for the gut, rather than the vague and unclear promises of standard probiotics.

The gut microbiome is an extremely complex community, and while science has learned a lot about the microbiome in the last 20 years, we are still really just scratching the surface. But simply put, the age-old recommendations of a healthy and balanced diet, low stress, and regular exercise are the best way to support your gut health! 

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice.

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