The Oxygen-Gut Dysbiosis Theory

My last podcast with Lucy Mailing, PhD shed light on a new theory to describe the process of gut dysbiosis that may be responsible for many different symptoms and diagnoses in the gut. This has impacted the education I am sharing with my clients in helping them heal their guts. Read excerpts of our interview below (edited for readability).

So let’s get to the main topic, the oxygen-gut dysbiosis theory. Tell me about the theory and the research today that supports it.

So first I saw a talk done by Dr. Sean Colgan at Experimental Biology Conference and essentially learned that butyrate is essential for the gut barrier. Most people know that, but it actually also helps to maintain hypoxia or a very low oxygen environment in the gut. So a healthy colon, large intestine, is virtually devoid of oxygen. It’s a very low oxygen environment, also known as anaerobic. And what happens is that anaerobic environments select for certain healthy bacteria. And what happens when we have gut inflammation is that the epithelial cells, the cells that line the gut, start to become inflamed and they start to leak oxygen into the gut. And when this happens, a lot of opportunistic pathogens like E. Coli, Salmonella and Enterococcus really like that oxygen, and they can use it to outcompete some of the beneficial microbes. So that oxygen leakage is really what is driving the dysbiosis.

And in fact, we do see this pattern across different chronic diseases: the most common pattern among all the dysbiosis that’s been observed is that there’s this overgrowth of facultative anaerobes, meaning microbes that can use oxygen when it’s present, and they do this at the expense of the beneficial microbes, including a lot of those butyrate producers that are so important for maintaining the gut barrier.

And what are some of those species or genera or phyla of beneficial butyrate producers?

I can name a few: Lachnospiraceae is one, Clostridia, a number of different Clostridia produce butyrate, Eubacterium, Roseburia. So there’s a number of different genera and families of butyrate producing bacteria, and essentially these are crucial to maintaining the health of that gut barrier because we if don’t have those butyrate producers, then we’re not getting an abundance of butyrate to fuel the epithelial cells and maintain them in a healthy state.

And so what is the result of that oxygenation and then the increase in these facultative anaerobes?

So just generally the facultative anaerobes tend to be much more inflammatory, so they tend to stress the gut, cause inflammation, intestinal permeability, and are also directly inflaming the gut epithelium. And what’s really interesting is that their inflaming the gut epithelium then leads to more oxygen produced in the gut. So it’s almost like these pathogens can hack our gut metabolism to feed themselves the substrates that they need to survive. And then it becomes a vicious cycle and they start to expand.

Right. And these are all typically from the phylum proteobacteria?

Yeah, most of them are in the phylum proteobacteria; that’s the most common that’s seen. And particularly the family Enterobacteriaceae is the most common to expand in this condition of increased oxygen leakage.

And more from our conversation on gut stool testing using metagenomics:

There’s a couple: Onegevity and Sun Genomics are two that I’ve explored. I’m liking Onegevity the best right now because they also allow you to download the raw data and then you can kind of parse through that as well. So that’s what I’m using currently. I was using uBiome, which was really great for 16s [a different form of gut microbiome testing] and you know, a lot less expensive. They’re totally gone now, so it’s not an option. So I haven’t found another 16s that I feel is reliable. So I’ve typically recently gone to the metagenomics instead . . . metagenomics is taking all of the genes in the sample and sequencing all of them and then matching them back up to databases so we can get down to the genus species and strain level and typically do so with a greater degree of accuracy.

And will Onegevity tell you your breakdown of these big phyla?

Yeah. Onegevity does show the phyla breakdown. They also show your butyrate-producing capacity, which is pretty cool. And they do have a brief pathogen screening profile. I’m hoping that they’re going to be expanding that soon.

And do they include fungi?

They do include fungi, yeah. At least in the raw data. I’m not sure how much they report in the visual reports at the moment.

And parasites or viruses or anything like that?

So they will detect them with the metagenomics, whether some of them will pop up on the visualization report that they give you. Some of them you might have to find in the raw data. So for example, things like Blastocystis hominis that are a little bit more, is it parasite, is it not, will be in the raw data, but wouldn’t necessarily show on what they choose to report at the moment, at least.

So let’s go back to my ridiculous potential overabundance of proteobacteria. And if I look at some of these great anaerobic butyrate producers, and in my reports, I got none of them. So other than doing a fecal transplant, is there any way I can get them back into my system?

So the question is, do you actually not have them or are they just at such low abundance that they weren’t detected by 16s? And I would guess since you’re relatively healthy and talking to me, my guess is that they’re there. They’re just not at as high of abundance as they could be or are maybe even not high enough abundance to be detected with 16s, especially if it was skewing with the proteobacteria. Some of the butyrate producers may have also come back lower than they should have, but essentially, you know, there’s a number of things that you can do too even if the bacteria have gone down to really low abundance. Improving the health of your gut and your diet will essentially help them to reflourish.

So the gut really is quite resilient. There are certainly instances where your butyrate producers could go completely extinct. And in that instance, the only way to get them back would be to do a fecal microbiota transplant. But for most people, if you’ve got low butyrate producers, it is possible to shift the ecosystem back to just allow those to flourish and become more abundant.

And how do you do that?

So I think the, the first step is really just to make sure you have the basic health behaviors in place. We can talk about all kinds of advanced gut interventions, but if you don’t have the basic, you know, healthy diet, exercise, sleep and stress management cupboard, then all the fancy gut treatments, advanced therapies are not going to move the needle nearly as much as any of those things. So that’s kind of the first step. And honestly, that will shift the microbiome quite a bit back in the right direction.

Any particular aspect of a healthy diet, since obviously so many people define that differently?

Yeah. I think the truth is we don’t exactly know what the best diet is for the gut microbiome, and I don’t think that there is one best diet for the gut microbiome. Everyone’s microbiome is different, and some people, you know, may respond really well to a ketogenic diet, whereas other people might do better with a diet that includes more plant foods. So generally I just talk about focusing on whole foods and making sure that you’re getting processed foods and refined sugars out of your diet for sure.

After that, it really is personal experimentation. And if your gut is really inflamed, then it might be beneficial, like I said earlier, to do a short term more hypoallergenic diet, like the autoimmune protocol, to remove some of those more inflammatory foods, at least for a time to facilitate that healing. Because healing, bringing down inflammation, is going to essentially stop that oxygen leakage, which is driving the dysbiosis.

And what about the role of fiber in there?

Yeah, so fiber can be really beneficial for some people, but for other people it’s just going to exacerbate inflammation. So it’s kind of nuanced. Again, fiber does seem to be important in some people and is a good way to increase production of butyrate. But something we haven’t really touched on yet is that in a ketogenic diet, even if you’re not getting quite as much fiber, you are getting beta hydroxybutyrate, which is one of the primary ketone bodies produced in the liver, and it can actually eat into the same pathway in the gut that fulfills.

So what if you had this typical overabundance of proteobacteria and oxygen dysbiosis thing going on? What would be the typical symptoms of that?

It really can manifest in a lot of different ways. So we’ve seen that basically this microbial signature of high proteobacteria and low butyrate producers is found across a wide range of different diseases: inflammatory bowel disease, irritable bowel syndrome, colorectal cancer. But even type 2 diabetes, obesity, psoriasis.

Okay, so you wouldn’t necessarily say, well, people like this typically tend towards diarrhea or less formed stool versus constipation?

No, not necessarily. Although I will say that I see it a lot in my clients that have persistent bloating and abdominal distension. That’s a very common one that I see, but it’s also probably skewed based on my client population.

And so in your article that you wrote about all this, you suggested the supplemental butyrate might be something that would turn around this state of dysbiosis. Can you talk a little bit about that?

Yeah, definitely. And I should say, I don’t think that supplemental butyrate alone will necessarily be able to overcome this dysbiosis. So I outlined a number of different things, both diet and lifestyle factors, and  supplemental things that could be useful in trying to prevent oxygen leakage into the gut and kind of shift back to a state of homeostasis, butyrate being one of those things though that’s really important. So essentially what’s going on is the oxygen leakage is happening partly because the epithelial cells that line your gut are starved for energy. And when they’re starved for energy, they’re not metabolizing butyrate if they don’t have it. So what they do instead is pull glucose from the bloodstream, and essentially this ferments to lactate, and that lactate leaks into the gut, in addition to the oxygen that is normally used through the metabolism of butyrate. So it’s really the fact that there’s not butyrate present, and that’s what means that the oxygen that’s flowing into epithelial cells from the blood doesn’t get used. And that’s when it ends up spilling out into the gut lumen and feeding the pathogens.

So essentially providing supplemental butyrate will mean that you’re providing the energy that the epithelial cells prefer. They’ll use more oxygen as part of their metabolism of that butyrate and won’t need to do this, essentially, anaerobic glucose fermentation. That’s going to produce lactate and end up not using up the oxygen, meaning that oxygen and lactate will leak into the gut and feed Salmonella, Enterobacteriaceae, and a number of those different proteobacteria. . . But when we’re talking about things like supplemental butyrate, or I even talked about in my article, the use of mesalamine, which is actually a pharmaceutical treatment for inflammatory bowel disease that I could think could be beneficial in some cases of severe dysbiosis. I’m certainly not recommending that to the average person trying to improve their gut health. I’m really recommending that when we’ve gone beyond the typical interventions.

Well I know we are running out of time, but I have one last question because you’ve mentioned glutamine, so is L-glutamine something you frequently supplement with or suggest people supplement with?

Occasionally. It really depends on the case. It has been shown to be beneficial in IBS, in randomized control trials. Typically that’s a dose of five grams given two, three times a day. So in some people, yes. I am a little bit more cautious in people who might have autoimmunity, because glutamine can stimulate the immune system, so it really is more of a case by case basis, whether I’ll recommend glutamine. And of course there’s plenty of ways to get glutamine from our diet. If you tolerate bone broth, broth is a great source of glutamine, as are a lot of those other messy animal parts.

And I didn’t ask about this, but what kind of dosages are you thinking about with the butyrate supplementation?

With butyrate, I think it’s really important to be using a dose that is more of a physiologic concentration. So a lot of butyrate salts out there, sodium butyrate, calcium butyrate, magnesium butyrate, you can buy are suggesting like a five gram dose. I prefer to use smaller doses and those that are more targeted to the colon. Again, I’m not a licensed practitioner, but in the evidence in reviewing the literature, it seems that lower doses of butyrate can be beneficial for healing the mucosa, whereas large, massive doses of butyrate might actually inhibit STEM cell proliferation in the gut and prevent wound healing. So I think butyrate supplementation is great in a lot of different conditions, but it needs to be done in a way that’s more mimicking the concentrations of butyrate that we would be getting if we had a healthy microbiome that was producing butyrate.

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