The Microbiome, Probiotics  and Gut Health

Luke Tulloch

The article below is adapted from a podcast episode transcript, so please forgive any spelling or continuity errors. You can listen below:

Why is the human microbiome important?

All right, so I think first up we should just talk about the function and role of the gut microbiome. We have a symbiotic relationship with the organisms in our gut due to a period of co-evolution. So we've spent millions of years evolving alongside these organisms that live within our gut. Some researchers have suggested categorizing the sum of our genetic parts as one genome called the holo-genome, and that's how intricately tied we are with these organisms in our gut. So some people sort of consider them part of the larger organism that makes up a human and other people consider them a little bit separate.

But regardless, these organisms as a whole are referred to as the microbiome or microbiota. And we have multiple types of organisms that are encapsulated within this, including things like bacteria, eukaryotes and prokaryotes, which are the different sort of classes of single celled organisms that exist outside of the multi multicellular organisms such as humans and animals. Now, there is a huge number of these within our guts could be more than a hundred trillion bacterial cells in the gut alone. And at the time of recording, I believe there are over a thousand different identified species and probably quite a lot more. At this point, I wouldn't be surprised if there were 1500, 2000 or more. Any one individual may have around 150 different species within their gut. So a massive amount of material in there. And one of the cool little facts that often gets thrown around is that within our guts we actually have more cells than in the rest of our body combined.

Pretty interesting stuff. There are five major phyla of microbes in the body, and if you don't know what a phylum is the way it works is we go from life and that is categorized down into the domain, which then goes down into kingdom and then phylum. We then have class, order, family, genus, and species. So there are five major phyla, so pretty big, a broad umbrella of microbes within the body. We have Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria,
Fusobacteria. The main ones that we generally talk about, especially with probiotic supplementation, are Firmicutes and the Bacteroidetes. These are mostly found in the large intestine.

The way it works is that after material exits your stomach, it goes into the small intestine first. And then after that we go into the large intestine and then excretion. So most of the microbes are found in the large intestine. We do have small amounts that exist outside of that. In the mouth, in the small intestine and there are some disease States where you might get overgrowth in these areas. However most of it is located in the large intestine, and the reason why is because there's a favorable pH and variety of nutrients there that favors the survival and the flourishing of those bacteria. So you couldn't really have a large amount of bacteria living in your mouth or living in your small intestine because of the unfavorable pH conditions and the type of nutrients that are in there that are unable to really proliferate that type of life. 

The complexity and diversity of the bacteria in your gut tends to increase throughout your life. From when you're an infant and growing into adulthood, you'll tend to find that the complexity and diversity of the gut microbiome will increase. And then as we start aging again, you tend to find that that again starts to decline; the complexity and diversity of the microbes in your gut tend to reduce as you age. Again, this may be related to various health issues, but we'll get into that before we talk about probiotics.

Prebiotics vs probiotics

I think it's important to talk about the diet and prebiotic material, the differences that prebiotics are a material that we eat in the diet that form part of the food source for the microbes in our gut. Things like fiber and starch in particular will directly affect the microbiome. To give you an example, eating whole grains, whole grains will cause changes in the microbiome. That will then also cause a shift in the metabolic byproducts of the microbiome.

Examples of prebiotic foods

Most plant-based foods provide prebiotic material, and fibre supplements will have them too. Chicory and inulin are commonly found in gut supplements. Most fibrous vegetables, fruit or grains will contribute to prebiotic intake - garlic, leeks, asparagus, banana leaves, breads, pasta, oats, muesli and so on.

Why is the human microbiome important?

The microbiome itself is quite an interesting thing because it produces some metabolic byproducts just like when we digest our food and we excrete feces, except the excretions coming from our gut bacteria are things like short chain fatty acids.

Butyrate is a good example of this - it's quite an important short chain fatty acid that's a main fuel source for the colon cells. The colonocytes require butyrate as a main fuel source and therefore what we eat, even though it may not be directly related to containing any short chain fatty acids, can cause a shift in the microbiome and also provide prebiotic material that is then turned into short chain fatty acids that can in turn provide a fuel source for our colonocytes. And at the end of the day, what this actually does in terms of practical implications for our health is that it regulates the expression of the inflammatory pathways.

The gut and inflammation

The pro inflammatory cytokines work through that pathway. So we know that short chain fatty acids can inhibit the propagation of potentially harmful bacteria by controlling intestinal pH levels. We know that high animal protein or high animal fat diets will shift the microbiome populations more towards bacteroidetes and some other types rather than things like Ruminococcaceae and Lachnospiraceae, which are involved in the degradation of plant fibers.

Essentially what happens is our microbiome will evolve and change based on the foods we are eating. Whether this is a good thing or a bad thing is still yet to be determined, but we do know that you can cause shifts in the microbiome within a very short space of time based on what you're eating. So before we even start talking about probiotics and actually providing external bacteria to the gut, we should be thinking about what we're eating in terms of its prebiotic content and how that might influence firstly what type of bacteria we have and the relative population levels of those different strains in our guts, as well as the type of material that they're going to produce.

We should think about prebiotic and diet material first before we even start talking about probiotics. As a general rule, we see that low carbohydrate diets tend to reduce the numbers of bifidobacteria which have been associated with some positive health effects. And it seems as well that the Bacteroidetes seem to be associated with a high fat, low fiber diet, whereas the Firmicutes, these seem to correlate more with high fiber intakes. So there tends to be this kind of in reverse relationship where if you're eating a lot of carbohydrate and very low fat, you may get a more Firmicutes colonizing the gut. And if you get the opposite, very high fat and low fiber, you may get more Bacteroidetes.

Now, sometimes you'll see that there are supplement companies or various cures that will push the need for the ratio of Firmicutes and Bacteroidetes to be a certain way. And you know, there's possibly some merit to that based on the current research - But the fact is we don't really know for sure. It's kind of like saying, well, you know, all four legged creatures are dangerous or friendly, but just because a dog or a cat is friendly doesn't make a tiger and or wolf friendly. So it's very difficult to say, well, this massive group of bacteria is beneficial to health or not beneficial to health because there are far too many different strains that may comprise each of those groups within the gut. So just be aware that we can make some broad sweeping statements, but again, there's going to be individual response based on the exact strains that we're not really across yet in terms of the scientific literature.

In one particular study by Foerster et al, higher fiber diets were shown to produce a larger shift towards microbial diversity in a whole grain group compared to a group that was eating primarily red meat. Therefore, I think having enough carbohydrate and fiber would be best if you did want to promote microbial diversity, which has been shown to be generally beneficial.

Now it doesn't mean that that is the be all and end all. Of course, you may have other reasons for eating a low carbohydrate or a low fiber diet. However, that may be one of the main mechanisms why we see some of the benefits of a higher fiber diet (amongst other things -controlling satiety and hunger for example)

They may also be a case of altering our microbial diversity and providing some flow on effects via that that add up. So for example, we do see with a higher fiber intakes lower risk of bowel cancer. And there's an ongoing epidemiological study on diet and bowel cancer called E P I C, and it seems that for every 10 grams of daily fiber consumption, we see a decreased risk of bowel cancer. So whether that's one of the mechanisms are not, we're not quite sure yet, but it may be. We have seen association data that was widely reported in the media, mostly incorrectly that red meat causes cancer. One of the issues was heterocyclic amines.  Heterocyclic amines and nitrosamines are examples of known carcinogens
that are found in processed and red meat.

Now the implication for this and fiber intake is that those colon cells I spoke about before (the colonocytes) are exposed to these various compounds when you eat them and they can have a carcinogenic effect on the colonocytes. Now we spoke a bit about butyrate before - butyrate is as a metabolic byproduct by some of the bacteria in your gut when they eat fiber and starch and tends to have an antiinflammatory effect on those colonocytes. So it may be that we can buffer against this potential ingestion of carcinogens in processed and red meat by eating enough fiber alongside it. So this is one of the mechanisms where we can potentially find the right type of fiber intake and the right arrangement of species in the gut can help to protect us against a certain type of cancer.

Okay. So let's talk a little bit more about individual differences and gut bacteria. Because the individual composition of gut bacteria can vary a lot, even to the point where you may be able to identify individuals based on what their gut microbiome looks like. It's almost like a unique feature of ours, like a fingerprint.

We can also identify certain trends in the gut microbiomeacross cultures or geographical locations. All across the world, people have different compositions of their gut microbiome and seemingly healthy populations across the world or unhealthy populations across the world all tend to have different compositions of their gut microbiome. Given this, we don't really know exactly what a healthy microbiome should look like or what a standard or an average microbiome should look like which makes it very difficult to then recommend individual strains or strategies to alter the microbiome.

Well, we do have some associations with various disease states and the composition of the gut microbiome. So we know that specific microbes have been identified as being associated with positive outcomes as well as negative outcomes. Generally speaking, the positive health outcomes are associated with things like bifidobacteria, lactobacillus (and a few others, but those are the two main ones). You would recognize those as being quite prominent in most over the counter probiotic supplements. Obviously there were some that had been associated with negative health outcomes. Some of the ones that are pretty obvious are things like H pylori. And there are a few others as well, but they tend to have very overt effects. So if you don't have that, the story of H pylori, you should look it up. But essentially it was suspected by a researcher that this caused stomach ulcers.

And so he actually drank a test tube of the bacterium and gave himself stomach ulcers to prove to his colleagues that it did actually cause it - so that's a pretty direct cause and effect scenario. But if we're talking about things like autoimmune diseases or those type of ongoing recruitment type diseases of the system, it can be very difficult to identify whether the gut microbiome is actually playing a causative role in that or if there are simply associations.

Again, we don't quite have the granularity yet in our research to know for sure. One thing we do know is that bacterial diversity has been associated with health outcomes. Lower diversity in the number of species you have is associated with poor health outcomes and the opposite is true as well. But there are multiple factors involved. So we need to consider the diversity in species of your microbiome, the distribution.

In other words, which species exist in which ratios, and what are the metabolic outputs of those species - what are they producing? Those short chain fatty acids are an example of a metabolic output. And then you also need to consider interactions with your own environment. Your environmental stimulus and your dietary habits and your general lifestyle.

In some cases we may find that a particular microbiome could be perfectly healthy, given a certain environment, but may not be in another environment, and that's something that we're still pretty far away from identifying. Some of the stuff we have association four at the moment: Things like nutrient production. So short chain fatty acids and vitamins synthesis in the gut, we know that there are interactions with cancer proliferation as we spoke about.

We also know that there are massive oxidative stress or inflammation causative factors related to the gut. So a foreign bacteria have part of their cell wall that is called lipopolysaccharide. If lipopolysaccharide manages to get across the mucosal barrier of the intestines and into the body, it causes a huge oxidative stress and inflammatory response in the body. And so we know that anything related to inflammation or oxidative stress may have something to do with lipopolysaccharide. And if there is an issue with that getting across the the gut lining, then we've got a problem - whether that is very prominent or not is very difficult to say, but we know that that can happen. We know that there are associations in defense against pathogens of various types. So having your gut microbiome there can help mediate intestinal pH. It can help provide competition for energy substrates.

Let's say you have a "bad" bacterial strain in your gut, but you have heaps and heaps and heaps of "good" bacteria. Those good bacteria could simply just out-compete those bad bacteria and eat all the food, providing an environment that is not favorable to that bad bacteria and therefore the it never really gets a foothold. So that's another way that having a broad array of different microbes that are more or less healthy or neutral to your health in the gut can actually protect you against outside pathogens. As far as things like irritable bowel disease and cardiovascular outcomes, controlling inflammatory signaling is really important. Having diversity and the right type of species there is potentially important for ensuring that inflammatory signaling does not go get out of hand, that immune function is not compromised - so that immune system is not recruited without needing to be.

We also have some cardiovascular outcomes related to lipid and cholesterol metabolism in the actual intestines. And again, that is just related to the bacteria and you've got that metabolize and then produce a metabolic byproduct that we can then absorb and use.

Which probiotics are good for you?

Circling back to probiotic use - we can define probiotics as live micro organisms that are then administered to a host. We've only really identified a few specific organisms that I mentioned before that may be used successfully as probiotics - the bifidobacteria and the lactobacillus. These make up a really small proportion of the overall population of your gut, but they do seem to be a mildly beneficial for your health. We seem to see more bifidobacteria in higher proportions in infants that don't develop auto immune or gut diseases, but there are no specific health claims that are actually endorsed by any official body or anything too official.

We have to be really careful with association data. There is growing research in the area, so a lot more research being done and it is a very exciting time, but at the moment it's pretty equivocal, meaning there's a lot of data on both sides. There are methodological issues and it's really difficult to endorse any specific recommendations for an individual to supplement. One of the challenges in drawing conclusions on the efficacy of probiotics is that there is a lack of studies on specific individual species or strains. And of course there are so many to try and study, and when you're trying to introduce it to a microbiome that already has trillions of other organisms, it's very difficult to measure the effects and control the variables. So most meta-analyses that exist at the moment will group probiotics together as a supplement overall rather than looking at individual species or strains.

And so we have this really high heterogeneity and studies and there's potentially an overestimation of effect as a result. It may be that specific disease States could benefit from probiotics, but not general health, but we just don't really know yet.

Should you use probiotics after antibiotics?

Another thing that is quite interesting that you may have seen on my Instagram lately is that we've seen often doctors or nutritionists or trainers or whatever are recommending using probiotics after antibiotic use. So the idea being that the antibiotics will indiscriminately kill  a lot of the bacteria in your gut, and then you try and repopulate those bacteria or help it along by using probiotics either alongside or afterwards. Now there has been some data to show that this is a little bit helpful, but recently there's been some studies come out that show that in the first place, some people don't really respond very well to probiotics.

They don't actually cause any colonization of the gut. So they are waste of time taking them and in people that they do colonize, it may be that it actually takes longer to recover your original state of gut bacteria. So what these researchers did is they took a sample of the gut bacteria of their subjects. They gave them a course of antibiotics and then one group got a placebo and another group got probiotic supplement, which was I think a generic six strain supplement, if I remember correctly. And the probiotic group took a longer than six months to recover the original profile of their gut microbiome. Whereas the people who got the placebo actually recovered fairly quickly. So it may even delay in, some people are returned to their normal gut bacteria. Now again it could be that it's very beneficial for some people but not for others.

But because everyone that is very different and there is such a huge number of these bacteria in your gut, it's very difficult to say what is going to work well for an individual and whether that will work well for multiple individuals or not. We're just not at the point of being able to individually prescribed that yet. I will also say that if you are taking probiotics, you don't really know exactly what you're getting in the supplement. We don't know how many live bacteria there actually are. By the time you've gotten that supplement off the shelf and swallowed the pill. So as a general rule, I don't recommend supplementing with probiotics. Now there's going to be exceptions to that rule where it's very helpful to some people, but, and as far as actually determining who it is helpful for and what exact strains they should take and, and what numbers, unfortunately, we're just not yet there yet with the science.

Now, I have no doubt that we will get there at some point, but we're not quite there yet. What I would recommend is making sure that your prebiotic intake is adequate to support whatever microbes you have in your gut at the moment. Any prebiotic consumption may actually just have a broad benefits of the overall microbe community rather than any specific species, but that's going to be our best bet to increase the diversity and support the bacteria that are currently in your gut.

Look to your diet as the main mechanism for altering your gut bacteria. And again, we're not trying to alter it in a specific way, but just ensuring that there is enough prebiotic material in there, whether you are eating low carb or high carb would probably be the best way to go because we do know that that has some sort of measurable effect on outcomes such as colorectal cancer.

I guess the idea is that there's a lot of really exciting stuff coming out about gut health, but we just don't know enough to prescribe anything individually just yet. But hopefully in the future we'll have a lot more interesting stuff coming out that is actionable.

Thanks for reading,

Luke.