Ketogenic diets and gut microbiome health

I need everyone reading this blog article to understand that a ketogenic diet is a valid, gut-healing diet. If you are trying to heal your gut with lots of prebiotic fiber, probiotic supplements, and much other rigamarole, that’s fine, and you can try to do it that way. But I don’t want people to be discouraged from using the ketogenic diet because they believe it is somehow inherently unfavorable to the gut microbiome. The research does not support that stance and, quite frankly, I would argue shows the opposite.

There are many reasons why you may want to heal your gut. You may have symptoms of leaky gut, small intestinal bacterial overgrowth, neurotransmitter imbalances you feel are gut-related, IBS, Crohn’s disease, or other autoimmune disorders that you have researched and feel are related to leaky gut or an unfavorable gut microbiome balance.

And because I am all about you learning all the ways you can feel better, I think it is important that you learn how a ketogenic diet affects the gut microbiome. We know ketogenic diets have powerful effects on neurology in particular and some of the underlying mechanisms that we understand. But when we look at the changes in the microbiome and how exactly the changes in gut microbes that happen on the ketogenic diet (or any diet for that matter) lead to changes throughout the body’s systems, we just don’t know it all yet.

Bottom line. If anyone tells you otherwise, they are premature in their assertions. Nobody on the planet can predict the complexity going on in the gut microbiome and all the inter-related aspects of how this affects the body. It is a mystery. And anyone who tells you otherwise at this stage of the game is, as far as I understand it, potentially over-reaching the current level of research. Our level of knowledge about the gut microbiome is mostly associational. We see connections, and we only hypothesize possible mechanisms. A lot more research needs to be done.

If you are interested in the gut microbiome, I get it. It’s super fascinating. And I want you to understand how a ketogenic diet modifies it. Because of the focus of this blog, I will provide an outline of the associations researchers have found between the gut microbiome and the effects of a ketogenic diet on neurological disorders. This does not mean that there are no important associational observations in other disorders (e.g., obesity, cancer). It means that your exploration of how the ketogenic diet might alter microbiota in a favorable way for these conditions will have to take you elsewhere.

So let’s get started!

Bear with me as I outline some of the basics.

Microbiome Basics

Your gut microbiome refers to a host of different types of microorganisms that colonize the gastrointestinal tract, from your mouth all the way down to the anus. These microbes consist of bacteria, viruses, fungi, and others, and the genetic components of all these interesting creatures. These little creatures have their genes, expressing those genes based on their environment, and they have their own epigenetic expressions of those genes. See how complicated this gets?

In 2019 there were 150,000 and 92,143 distinct microbial strains in two large meta-analyses identified. But until researchers understand how the genetic expression of microbes interacts in different environments in the gut and different disease states, we cannot know how they influence functions.

The field still does not have a grasp on the scope of the microbiome’s genetic content—in the gut and otherwise—a question crucial for understanding microbial function in the context of host disease

Tierney, B. T., Yang, Z., Luber, J. M., Beaudin, M., Wibowo, M. C., Baek, C., … & Kostic, A. D. (2019). The landscape of genetic content in the gut and oral human microbiome. Cell host & microbe26(2), 283-295. https://doi.org/10.1016/j.chom.2019.07.008

We do know some things, though. At least we think we do because they appear to be fairly consistent in findings. We know that gut microbiota exerts an influence on our ability to metabolize carbohydrates and break down our amino acids. They help us extract calories and unlock nutrients that are normally not easily accessible. They help us synthesize vitamins, heal and protect our gut walls (mucosal integrity) and regulate our immune system.

I am in no way arguing that the gut microbiome is somehow unimportant.

But I am arguing that maybe you and your healthcare providers do not know enough about it to actually attempt to tinker with it. That perhaps, for people who are really ill and have significant symptoms, the real intervention that is going to heal the gut and provide a favorable microbiome might just be the one where you change your diet, as opposed to constantly taking a lot of functional stool analysis tests, prebiotic fibers that may be irritating your gut, and expensive probiotic formulations that cannot get good colonization anyways because you don’t have an environment down there they can thrive in.

Your gut microbiome is affected by your age, genetics, and the environment you live in, but there is nothing as powerful and shaping to the human microbiome as diet. Gut microbes eat what you eat, and they derive their nutrition from your macronutrients (e.g., fat, protein, carbohydrates). What you eat feeds some microbes better than others. Some of those microbes like to thrive on fat, and some of them want their fuel to be carbohydrates, for example. Ketogenic diets will understandably feed and increase the number of microbes that prefer fat as their macronutrient.

Ketogenic diets tend to be higher in fat and low in carbohydrates. When we see people adhere to a well-formulated ketogenic diet (enriched with protein and animal fats), the microbiome is seen to be Bacteroides dominated. When we see people on high carbohydrate diets, we see a predominance of Prevotella microbiomes.

And this is part of why I had reservations about writing this article. I just got done explaining that these interactions are very complicated, and we don’t know as much as we think. But now, I will tell you what we think we know about these two different microbiome species based on dietary macronutrient intake.

Here is what we learn when we do a cursory search about Bacteroides, the type of microbiome predominance we see in ketogenic diets.

Bacteroides species also benefit their host by excluding potential pathogens from colonizing the gut.

https://en.wikipedia.org/wiki/Bacteroides

As proven commensals, mutualists, and beneficial organisms, they not only play the role of “Providers” for the host and other microbes residing close to them, but also assist the host by providing numerous health benefits.

Zafar, H., & Saier Jr, M. H. (2021). Gut Bacteroides species in health and disease. Gut Microbes13(1), 1848158. doi: 10.1080/19490976.2020.1848158

And now let’s see what a quick search uncovers regarding Prevotella:

The gut commensal Prevotella bacteria contribute to polysaccharide breakdown, being dominant colonisers of agrarian societies. However, studies also suggested a potential role of Prevotella species as intestinal pathobionts.

Precup, G., & Vodnar, D. C. (2019). Gut Prevotella as a possible biomarker of diet and its eubiotic versus dysbiotic roles: a comprehensive literature review. British Journal of Nutrition122(2), 131-140. doi: 10.1017/S0007114519000680

This looks pretty obvious that one is more beneficial to human health and the other is less so. But as I am trying to tell you, it’s complicated. Bacteroides, which look like good bacteria, don’t necessarily act that way if they escape the gut from leaky junctions (aka leaky gut). And again, how these microbes react and how they affect your physiology depends on your gut environment, age, genetics, disease state, etc. But for the sake of ease in the discussion, let’s just conceptualize one of these types of bacteria as potentially more beneficial than the other. I know some of you will want to categorize one as good bacteria and one as bad bacteria, but try not to do that if you can so, we can get the most out of this discussion.

Usually, we see an increase in the Bacteroides species in diets high in fiber or polysaccharides. Make a note of that because it will be important to our discussion later in this blog post when we discuss fiber and butyrate. 

Your microbiome can facilitate bidirectional communication between your gut and your brain. It’s like your brain and your gut microbiome are playing a game of telephone with a soup can off and on constantly. The phone cord in this analogy is not just one cord or communication line. The line of communication between the microbiome and the brain includes the vagus nerve and immunological and endocrine mechanisms.

We don’t know a lot, but let’s see what we do know about the alteration of gut microbiota using the ketogenic diet with a couple of populations in which it is used often to treat neurological symptoms.

Epilepsy

Infants and adults with epilepsy have been shown to have alterations in the gut microbiome compared to healthy controls. The general observation is that they have a higher proliferation of Proetobacteria and a lower number of Bacteroides. In studies that use a ketogenic diet to treat refractory epilepsy, a change in the gut microbiome can be observed after as little as 1-week and decrease in the abundance of Proetobacteria and Chronobacter in stool samples to levels seen more comparable to healthy controls. In studies observing the effects of the ketogenic diet on the microbiome that run for longer amounts of time (see Zhang et al. 2018), there is seen an increase in Bacteroides and a decrease in Ruminococcaceae, Faecalibacterium, Actinobacteria, and Leucobacter in those who responded and experienced reduced seizure activity. Responders to the ketogenic diet also had lower Clostridium XIVa, AlistipesHelicobacterBlautiaEggerthella, and Streptococcus

The findings of these studies and others looking at microbiome alterations in populations with epilepsy just tell us what we already know. The findings of changes in gut microbiome on the ketogenic diet (or any other diet for that matter) reveal inconsistent findings with different microbial alterations occurring in different cohorts of patients. And as usual, it is thought this occurs because of differences in age, diet adherence and composition, medication use, and genetics of the person eating it.

In the case of epilepsy, it is thought that the power of the ketogenic diet to alter the gut microbiome in a very short period is an important factor in its mechanism of action to treat seizures. One mechanism thought to be at play is the increase of certain microbes (A. muciniphila and Parabacteroides) species, which lead to a decrease in certain amino acids that leads to an increase in GABA and an improvement in the GABA:Glutamate ratio. If you have read any of the blog posts about ketogenic diets and any particular disorder, you will know how important a favorable GABA:Glutamate ratio is for a happy brain. And if a ketogenic diet can possibly modify your gut microbiome to improve that ratio? Well, that would make it a very gut-friendly diet and brain-friendly diet, indeed. 

Alzheimer’s Disease

The microbiome is altered in people with Alzheimer’s disease compared to healthy controls. Some of the observations include greater amounts of Antinobacteria, Ruminococcaceae, and Subdoligranulum, but a decrease in Bacteroides (Remember these little guys from earlier? We are conceptualizing this species as generally more favorable as long as it stays where it belongs).

When we provide a ketogenic diet to elderly people with Mild Cognitive Impairment (MCI), which signals many people’s early stages of progressive dementia, there are changes. There is a decrease in Bifidobacterium species and increases in Enterobacteriaceae and Akkermansia, not surprising fecal butyrate concentrations. 

Does the word butyrate look familiar? It should. 

We are told it is the preferred fuel of the gut enteric cells and is essential for gut health. It’s why your functional medicine person is telling you to eat fiber so that it can ferment into the short-chain fatty acid butyrate to improve your gut health and specifically help you heal that leaky gut problem. 

You know what provides butyrate? Ketones.

Paoli, A., Mancin, L., Bianco, A., Thomas, E., Mota, J. F., & Piccini, F. (2019). Ketogenic diet and microbiota: friends or enemies?. Genes10(7), 534. https://doi.org/10.3390/genes10070534

But do you know what food has the most butyrate, ready to be used by your gut and doesn’t even need to be broken down? 

In fact, butter is one of the richest butyric acid food sources with a naturally inherent supply of 3-4% of its fat content as butyric acid.” Cavaleri, F., & Bashar, E. (2018). Potential synergies of β-hydroxybutyrate and butyrate on the modulation of metabolism, inflammation, cognition, and general health.

Cavaleri, F., & Bashar, E. (2018). Potential synergies of β-hydroxybutyrate and butyrate on the modulation of metabolism, inflammation, cognition, and general health. Journal of nutrition and metabolism2018. doi: 10.1155/2018/7195760

Yep. Butter. A staple of many people’s well-formulated ketogenic diet. And do you know why else that word looks familiar? Because one of the ketone bodies you produce on a ketogenic diet is called Beta-Hydroxybutyrate, which also has beneficial effects on the gut.

Human colonic microbiotas with high growth activity demonstrate efficient utilisation of DBHB for increased butyrate production, which affords health benefits.

Sasaki, K., Sasaki, D., Hannya, A., Tsubota, J., & Kondo, A. (2020). In vitro human colonic microbiota utilizes D-β-hydroxybutyrate to increase butyrogenesis. Scientific reports10(1), 1-8. https://doi.org/10.1038/s41598-020-65561-5  

Other studies that look at ketogenic dietary intervention for people with Mild Cognitive Impairment (MCI) show improvements in the number and diversity of gut microbiome species, which is negatively correlated with the expression of tau plaques, known to appear as part of the disease process in those with Alzheimer’s disease and other forms of dementia. 

Conclusion

So if someone tells you that eating a ketogenic diet will reduce the diversity and health of your microbiome, you need to remember what you read here. If someone tells you that you won’t be able to heal your leaky gut using a ketogenic diet, again, remember what you have read here. Those assertions are not supported by the research literature thus far regarding microbiome alterations, gut health, or anything else relevant to the biochemistry of what is happening. 

More likely, you have encountered someone holding onto some fiber and plant dogma who has trouble reconciling their past knowledge with what is currently coming out in the research literature.

But yes, let’s talk plants. Let’s say you don’t do butter, and maybe you are not doing a ketogenic diet for brain health and therefore are concerned maybe you won’t make enough of the ketone beta-hydroxybutyrate to feed your cells and microbiome. Maybe you are just low carb to lose weight or something like that. Well, that’s OK, too. Because as long as you are doing a well-formulated ketogenic diet consisting of whole foods with low-carb veggies, you are golden. 

Low carb veggies are full of prebiotic fiber and often high in sulfur content, helping your gut to maintain its mucosal barrier in the intestine and upregulating glutathione production to help heal intestinal inflammation.

So, if you want to keep on keeping on with your fiber, you do that! I support your decision to cover all of your bases. 

Conclusion

So if you are using a ketogenic diet to improve your mental health or treat your neurological symptoms, please rest assured that the following is true, based on the current literature at the time of this writing, in regards to ketogenic diets and their effects on the gut:

  • You are not destroying your gut lining or impairing its healing. 
  • You are not upsetting any favorable ratio of beneficial microbiome species. Most likely you are improving your existing one.
  • You are not impeding your microbiome diversity in any negative way that has negative health effects.

I do not have a lot of blog posts to steer you towards the gut microbiome, as I am mostly focused on educating about what is going on from the neck up, even though I am aware of how these things are all quite connected. But I do have a small section on the gut microbiome in this article below because people suffering from depression often want to know more about the effects of the microbiome on their mental health.

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Because you have the right to know all of the ways that you can feel better.


References

Cavaleri, F., & Bashar, E. (2018). Potential Synergies of β-Hydroxybutyrate and Butyrate on the Modulation of Metabolism, Inflammation, Cognition, and General Health. Journal of Nutrition and Metabolism, 2018, 7195760. https://doi.org/10.1155/2018/7195760

Li, D., Wang, P., Wang, P., Hu, X., & Chen, F. (2019a). Targeting the gut microbiota by dietary nutrients: A new avenue for human health. Critical Reviews in Food Science and Nutrition, 59(2), 181–195. https://doi.org/10.1080/10408398.2017.1363708

Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes. (n.d.). Retrieved May 1, 2022, from https://www.science.org/doi/abs/10.1126/science.1208344

Mu, C., Shearer, J., & Morris H. Scantlebury. (2022). The Ketogenic Diet and Gut Microbiome. In Ketogenic Diet and Metabolic Therapies: Expanded roles in health and disease (2nd ed., pp. 245–255). Oxford University Press.

Nagpal, R., Neth, B. J., Wang, S., Craft, S., & Yadav, H. (2019). Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer’s disease markers in subjects with mild cognitive impairment. EBioMedicine, 47, 529–542. https://doi.org/10.1016/j.ebiom.2019.08.032

Olson, C. A., Vuong, H. E., Yano, J. M., Liang, Q. Y., Nusbaum, D. J., & Hsiao, E. Y. (2018). The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet. Cell, 173(7), 1728-1741.e13. https://doi.org/10.1016/j.cell.2018.04.027

Paoli, A., Mancin, L., Bianco, A., Thomas, E., Mota, J. F., & Piccini, F. (2019). Ketogenic diet and microbiota: friends or enemies?. Genes10(7), 534. https://doi.org/10.3390/genes10070534

Precup, G., & Vodnar, D.-C. (2019). Gut Prevotella as a possible biomarker of diet and its eubiotic versus dysbiotic roles: A comprehensive literature review. The British Journal of Nutrition, 122(2), 131–140. https://doi.org/10.1017/S0007114519000680

Sandoval-Motta, S., Aldana, M., Martínez-Romero, E., & Frank, A. (2017). The Human Microbiome and the Missing Heritability Problem. Frontiers in Genetics, 8. https://www.frontiersin.org/article/10.3389/fgene.2017.00080

Sasaki, K., Sasaki, D., Hannya, A., Tsubota, J., & Kondo, A. (2020). In vitro human colonic microbiota utilises D-β-hydroxybutyrate to increase butyrogenesis. Scientific Reports, 10(1), 8516. https://doi.org/10.1038/s41598-020-65561-5

Tierney, B. T., Yang, Z., Luber, J. M., Beaudin, M., Wibowo, M. C., Baek, C., Mehlenbacher, E., Patel, C. J., & Kostic, A. D. (2019). The Landscape of Genetic Content in the Gut and Oral Human Microbiome. Cell Host & Microbe, 26(2), 283-295.e8. https://doi.org/10.1016/j.chom.2019.07.008

What Is Butyrate And Why Should You Care? (n.d.). Retrieved May 1, 2022, from https://atlasbiomed.com/blog/what-is-butyrate/

Zafar, H., & Saier, M. H. (n.d.). Gut Bacteroides species in health and disease. Gut Microbes, 13(1), 1848158. https://doi.org/10.1080/19490976.2020.1848158

Zhang, Y., Zhou, S., Zhou, Y., Yu, L., Zhang, L., & Wang, Y. (2018). Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Research, 145, 163–168. https://doi.org/10.1016/j.eplepsyres.2018.06.015

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