Is a high-fat or ketogenic diet bad for your gut?

BY LUCY MAILING, MD/PHD STUDENT

Ketogenic diets are becoming increasingly popular for everything from weight loss to cancer therapy. Many people have expressed concern about the impact that this has on the health of the gut and the gut microbiome. But does a high-fat diet really spell disaster for the gut? In this article, learn why animal studies are misleading, what the current research says, and why ketosis may even be able to improve gut health in some cases.

If you’ve been reading my blog for a while, you know that I’m a proponent of a low-carb, high-fat or ketogenic diet for many different conditions. Keto is becoming increasingly popular for weight loss, blood sugar regulation, neurodegenerative diseases, and even as a component of cancer treatment. Others, including myself, choose a ketogenic diet for the mental clarity and enhanced productivity.

In recent months, I’ve received a lot of questions as to the effects that this has on the health of the gut and gut microbiome. It seems there is this widespread notion out there that the only thing that feeds beneficial gut microbes is complex carbohydrates, and that if we don’t have butyrate from the fermentation of dietary fiber, our gut barrier suffers, too.

But is this really true? In this article, I’ll dive into the research and provide a complete discussion of the evidence, including what we don’t know.

We don’t really know what constitutes a “healthy” microbiome

New technologies and an increasing interest in gut health in recent years have dramatically increased our understanding of gut microbes, and commercial companies now allow anyone to get a peek at the microbial world that resides in their gut. Unfortunately, the excitement has gotten ahead of the research, and the truth is, we know very little about what constitutes a “healthy” gut microbiota.

Pick any two people, and on average they will only share about a third of their gut microbiota. The other two-thirds of their gut community will vary significantly depending on their genetics, geographical location, history of antibiotic and medication use, mode of birth, diet, and other factors that are likely yet to be discovered. We really don’t have enough information to say that one person’s “two-thirds” is any better than another person’s “two-thirds”, unless one of them has an overgrowth or infection with a known pathogen.

You might say, well, couldn’t we look at microbial diversity? Or stability of the community? While it’s generally believed that diversity and community stability are key components of a healthy gut ecosystem, even these can sometimes be associated with diseased states.1,2 And some of the keystone “beneficial” microbes recognized by many to be crucial for microbiome health, such as Bifidobacterium, are completely absent from the guts of traditional cultures like the Hadza,3 yet these populations are virtually free of chronic disease.

We’ll explore the evolutionary perspective more in the next section.

The gut microbiome has evolved with us – often in the context of periodic ketosis

Our relationship with our gut microbes today is the product of thousands of generations of co-evolution. For millions of years, evolution hasn’t just been acting on our 23,000 human genes, it’s been acting on the nearly 4 million genes (both human and microbial) that are present in and on our bodies.4 We are who we are today because of how we evolved with our microbes.

The environment we evolved in required regular adaptation to changing conditions. Our ancestors did not always have ready access to food and would have undergone occasional bouts of fasting when food was scarce. As such, our bodies have the ability to burn and use carbohydrates when food is plentiful, and to turn dietary fat or stored body fat into ketones for energy when food or carbohydrates are scarce. This is called metabolic flexibility.

So the real question is: Why would our bodies have the metabolic flexibility to deal with the shifting availability of foods – and our gut microbiome not have the same metabolic flexibility? Would our ancestors really have developed a “diseased” microbiome every time starchy carbohydrates became scarce? I think not.

Let’s also consider traditional cultures like the Inuit. Did the Inuit, who ate very few plant foods, really have an unhealthy microbiome? Or did they have a microbiome that was uniquely adapted to their diet? Did they have rampant gut permeability and inflammation from their high-fat diet? Or did their gut also have a form of metabolic flexibility that allowed them to survive on primarily animal protein and fat?

We’ll discuss all of the underlying mechanisms in a moment, but my point here is this: A “healthy” microbiome is simply the microbiome that you have when you’re healthy. And what’s healthy for you may not be healthy for someone else.

This is part of the reason why I always emphasize looking at the overall gut environment and current symptoms when helping clients with gut issues. If someone has low gut microbial diversity but feels fantastic, treating the gut may do more harm than good.

But enough on that – let’s dive into the data.

Animal studies that use a “high-fat diet” are misleading

If you search any database of the scientific literature, you can find over a hundred studies that show feeding animals a “high-fat diet” leads to massive gut dysbiosis, gut permeability, and systemic inflammation. People often cite these studies to suggest that a high-fat diet is also likely to be unhealthy for the human gut microbiome.

Look closer at the methods though, and you’ll see that the “high-fat diet” used in most animal studies is more accurately a diet high in refined soybean oil, lard, and refined sugar, and very low in fiber.5 Dr. Craig Warden, professor at UC Davis, has called this “the mouse equivalent of pork rinds, ribs, and coke,”6 suggesting that this “high-fat diet” is much more reflective of the Standard American Diet than any carefully-crafted ketogenic diet.

Furthermore, human metabolism can easily adapt to a diet higher in fats or carbohydrate. The natural diet of a mouse, on the other hand, is low in fat and high in carbohydrates, so it’s not all that surprising that mice develop issues when eating a diet that is so poorly matched with what they evolved to eat.

Moreover, the strain of mice most commonly used for such studies, the C57Bl/6 mouse, has been genetically selected for its ability to put on weight and raise glucose in response to a “high-fat diet”. While humans tend to show greater weight loss in response to low-carbohydrate diets, C57Bl/6 mice have greater weight gain and metabolic disruptions on low-carb diets. After observing this, principal investigators Dr. Richard Feinman and Dr. Saihan Borghjid concluded:

“The results suggest that rodent models of obesity may be most valuable in the understanding of how metabolic mechanisms can work in ways different from the effect in humans.” 7

In other words, the idea that we can translate any findings in these selectively bred mice fed a “high-fat diet” to health-conscious humans eating a ketogenic diet is just absurd, and a gross misrepresentation of the research.

So, let’s look at the human research instead.

(A ketogenic) diet rapidly and reproducibly alters the human gut microbiome

In 2014, David et al. published a study in the journal Nature where they put healthy human volunteers on a short-term plant-based diet or animal-based diet and demonstrated that distinct gut microbial communities emerged within as little as three days.

This was a pivotal study in microbiome research and one I’ve been aware of for some time (it’s been cited over 2,700 times since 2014), but it wasn’t until I was doing the research for this article and happened to look at the supplementary data that it dawned on me: the animal-based diet was ketogenic!

While the plant-based diet included 300 grams of carbohydrate per day from cereal, vegetables, rice, lentils, and fruit, the animal-based diet included less than 3 grams of carbs per day, with 30% calories from protein and 70% calories from fat coming from eggs, meat, and cheese. This macronutrient ratio is consistent with a ketogenic diet. The researchers even measured ketones in the urine and confirmed that the subjects were in ketosis by day two of the animal-based diet.

In other words – this study is the study that many people are saying we don’t have.

So what did they find? Participants on the animal-based ketogenic diet saw an increase in microbial diversity. They also saw an increase in the relative abundance of bile-tolerant microorganisms like Bilophila, Alistipes, and Bacteroides spp. and a decrease in the relative abundance of microbes known to metabolize complex dietary plant fibers, such as Roseburia, Eubacterium, and Ruminococcus spp. This is not all too surprising.

In line with my evolutionary argument, the authors write:

“Our findings that the human gut microbiome can rapidly switch between herbivorous and carnivorous functional profiles may reflect past selective pressures during human evolution. Consumption of animal foods by our ancestors was likely volatile, depending on season and stochastic foraging success, with readily available plant foods offering a fallback source of calories and nutrients. Microbial communities that could quickly, and appropriately, shift their functional repertoire in response to diet change would have subsequently enhanced human dietary flexibility.”

In other words, our gut microbiota is simply adapting to the current availability of different food sources – it’s not necessarily becoming any more or less pathogenic by the amount of carbohydrate or fat in the diet.

Ketogenic diet-induced changes in the gut microbiome may be protective in multiple sclerosis

What about longer-term studies? One study published in the journal Frontiers in Microbiology in 2017 examined the long-term effects of a ketogenic diet on the fecal microbiota in 25 patients with multiple sclerosis.8

Multiple sclerosis (MS) is an autoimmune disease that affects the nervous system. Like many autoimmune diseases, MS is associated with gut pathologies. In fact, some researchers suspect that gut dysbiosis and intestinal permeability may precede the development of autoimmunity in the first place.9 Thus, it follows that if a ketogenic diet can significantly improve symptoms of MS,10 it’s probably not harming the gut, and may even be improving gut health.

So what did the study find? Patients with MS tended to have reduced Roseburia, Bacteroides, and Faecalibacterium prausnitzii at baseline compared to healthy individuals. They then went on a ketogenic diet for 6 months. The authors write:

“The effects of a ketogenic diet were biphasic. In the short term, bacterial concentrations and diversity were further reduced. They started to recover at week 12 and exceeded significantly the baseline values after 23–24 weeks on the ketogenic diet.” 8

This suggests that, while short-term dietary changes can rapidly shift the composition of the gut microbiota, we may need to look at long-term dietary changes and collect samples at multiple time points to determine the true effect of a dietary intervention.

Unfortunately, this study did not measure symptoms or any other indices of gut health, so we can’t know whether the ketogenic diet was beneficial. To explore whether a ketogenic diet is causally beneficial for the gut microbiome, we’ll have to return to well-designed animal studies.

The gut microbiome mediates the anti-seizure effects of the ketogenic diet

Ketogenic diets are frequently used to treat epilepsy that is unresponsive to drug treatments. While incredibly effective, exactly how the ketogenic diet confers benefits on brain activity remained elusive for decades. However, a new study published in the journal Cell in May 2018 suggests that the beneficial effects of the ketogenic diet are mediated through the gut microbiome!11 In other words, if a ketogenic diet didn’t change the microbiome, it wouldn’t be effective at preventing seizures.

The study was performed in a mouse model of epilepsy (using different strains than the one I mentioned earlier). Like previous studies, they were able to show that feeding the mice a ketogenic diet protected them against seizures. They further demonstrated, however, that treating the mice with broad-spectrum antibiotics abolished the protection against seizures. Similarly, germ-free mice, which are raised in sterile incubators and have no gut microbiome, were not protected against seizures, even when consuming a ketogenic diet.

Interestingly, the ketogenic diet in this study reduced microbial diversity but increased the abundance of Akkermansia muciniphila and Parabacteroides spp. The researchers wondered if these two microbes were responsible for the seizure protection and tried treating mice fed a normal high-carbohydrate chow diet with Akkermansia and Parabacteroides. Amazingly, this conferred protection against the seizures.

Further mechanistic experiments identified a bacterial pathway that elevated the ratio of the inhibitory neurotransmitter GABA relative to the excitatory neurotransmitter glutamate in the brain. GABA calms activity in the brain, so this explains the seizure reduction, and may also explain why many people find the ketogenic diet beneficial for reducing anxiety.

Won’t keto reduce your production of butyrate?

Now that we’ve covered all of the relevant human and animal experimental data that we have to date, I want to talk a bit about the mechanisms involved.

First, we know that fermentable carbohydrates are required for the production of short-chain fatty acids. The short-chain fatty acid butyrate is well-known as the “preferred” fuel source for gut epithelial cells. In most modern humans, it provides about 70 percent of the energy requirements for colon epithelial cells. And we need a regular supply of butyrate to maintain barrier function…right?

Nope. Turns out that there are several other molecules that can perform many of the signaling functions of butyrate AND serve as a source of fuel for the gut epithelial cells! In fact, this idea of a “preferred” fuel source may be skewed from studying people (and rodents) who are eating large amounts of carbohydrates. Butyrate production will undoubtedly be reduced on a ketogenic diet, but other molecules can take its place to help maintain gut barrier function.

Ketone bodies and isobutyrate can replace butyrate

There are three molecules that can replace butyrate: isobutyrate, acetoacetate and beta-hydroxybutyrate.

Isobutyrate is a metabolite of protein fermentation that is typically produced in much lower levels than butyrate. When butyrate is absent, isobutyrate can be taken up by from the gut lumen by gut epithelial cells and metabolized for energy. Isobutyrate was found to be elevated in the study I mentioned above in those consuming the animal-based ketogenic diet.12

Moreover, isobutyrate can stimulate the same receptors as butyrate in the gut (GPR41, GPR43, and GPR109a) that lead to mucus secretion, antimicrobial peptide release, and immune regulation.13 And while isobutyrate may be produced at lower levels on a moderate-high-protein diet than butyrate would be produced on a high-carbohydrate diet,12 isobutyrate has been shown to be a more potent stimulator of GPR41 (FFAR3), one of the primary receptors for butyrate, than butyrate itself!14 In other words, what isobutyrate lacks in concentration, it may make up for in potency.

The other two molecules, acetoacetate and beta-hydroxybutyrate (βHB), are the two major ketone bodies produced by the liver during a ketogenic state. Like butyrate, βHB can also stimulate GPR109a, reducing intestinal inflammation. Most notably, however, both βHB and acetoacetate are intermediates in the pathway for butyrate metabolism. In other words, when butyrate is taken up by gut epithelial cells, it is actually converted into βHB first, and then acetoacetate, before being broken down further for energy. See the figure below:

Now, cutting out three steps of metabolism doesn’t seem like a big deal, until you realize that hydrogen sulfide (H2S) impairs the enzyme that catalyzes the first step of butyrate oxidation,15 and many individuals with gut dysbiosis have excess production of H2S.

Getting your substrates from the blood also doesn’t seem to have much of an advantage, until you consider that many people with inflamed guts have mucosal damage where butyrate uptake is impaired.

So what does this mean? If you’re generally healthy and have a healthy gut, butyrate is well equipped to deal with all your gut’s needs, no ketones needed.

However, if you:

  • have ulcerative colitis or other mucosal damage, where butyrate uptake is impaired,
  • have high levels of hydrogen-sulfide producing organisms, where the first step of butyrate oxidation is impaired (prevalent in those with IBS-D),
  • have gut dysbiosis characterized by a lack of butyrate-producers, or
  • have carbohydrate malabsorption and are on long-term low-FODMAP or SCD, resulting in reduced butyrate production,

it may be wise to try therapeutic ketosis to support gut epithelial cell metabolism, at least until treating the underlying gut pathologies and healing the gut lining.

Unfortunately, few studies have been performed on ketogenic diets for Crohn’s disease, ulcerative colitis, or irritable bowel syndrome. One case report found that a paleolithic, ketogenic diet induced complete remission in a young boy with severe Crohn’s disease.16 A second case report found that a low carbohydrate diet with ketone ester supplementation significantly reduced inflammation and improved quality of life in a patient with Crohn’s disease.17

Another study of 13 patients with diarrhea-predominant irritable bowel syndrome (IBS-D) found that 10 reported relief of symptoms during a 4-week ketogenic diet.18 Anecdotally, many people with ulcerative colitis have found relief from ketogenic diets, including popular health blogger and biochemist Robb Wolf.

To my knowledge, no studies have assessed the effects of ketones or a ketogenic diet on gut barrier function. This is certainly something I hope to study in my lab in the future.

But don’t high-fat diets increase LPS absorption?

Another common argument for avoiding high-fat diets is that they increase intestinal absorption of lipopolysaccharide (LPS), a molecule found in the cell walls of gram-negative bacteria. If LPS gets into circulation, it can cause low-grade, systemic inflammation.

To really understand this mechanism, we need to review how fats are digested and absorbed. When we eat fat, specialized cells in the small intestine release a hormone called cholecystokinin (CCK). CCK stimulates the gallbladder to secrete bile into the small intestine. Here, the bile acids surround fat molecules, helping to make them water soluble (much like dish detergent helps to emulsify oil).

It turns out that LPS has a high affinity for these water-soluble packages, called micelles. Micelles eventually diffuse toward the gut epithelium, where their contents (including LPS) are picked up by gut epithelial cells. The epithelial cells repackage the lipids and LPS into chylomicrons, which can then be exported to the liver via the lymphatics.

When we consume more long chain fatty acids, our body makes more of these chylomicrons, so more LPS can hitch a ride in this fashion.19 Indeed, fat-enriched meals have been shown to moderately increase serum levels of LPS in both mice and humans.20,21 While this is absolutely a real phenomenon and worth considering, I believe this is generally a non-issue for several reasons.

First, several studies suggest that the transport of LPS by chylomicrons may confer an advantage because it favors clearance of LPS by the liver, reducing the toxicity of LPS.22,23 Moreover, chylomicrons also have an innate ability to inactivate LPS.24 Altogether, the increased absorption of LPS appears to reduce inflammation in the gut mucosa.25

This is especially important since the primary mode of systemic exposure to LPS is not through fat absorption, but through a leaky gut! When the gut is permeable, large amounts of LPS can leak into the submucosa and bloodstream, causing localized gut immune responses and systemic inflammation.

Compared to full-blown intestinal permeability, chylomicron-induced LPS absorption is merely a drop in the bucket. (In fact, for those who are dealing with severe intestinal permeability, chylomicron-induced detoxification of LPS may even reduce inflammation enough to facilitate healing of the gut epithelium.)

Furthermore, if fat-induced LPS absorption was an issue, we would expect to see increased systemic inflammation in those fed a high-fat ketogenic diet. On the contrary, subjects fed ketogenic diets almost universally experience a reduction in systemic inflammation.26

Alright so, hopefully by this point, I’ve convinced you that high-fat diets are not to be feared for their lack of butyrate or increased absorption of LPS. In the next section, we’ll see how bile acids might also contribute to a healthier gut.

Bile acids are critical for gut health

Some people have also suggested that a high-fat diet might be detrimental to the gut microbiota and gut barrier because it stimulates increased secretion of bile acids. The more fat you eat, the more bile is released into the small intestine.

Indeed, some studies have shown that sustained exposure of the gut barrier to high concentrations of bile acids results in intestinal permeability. However, physiologic doses of bile acids have been shown to support barrier function, inducing the secretion of mucus from goblet cells, promoting epithelial cell migration, and boosting gut innate immune defenses.27

Bile acids also have antimicrobial properties, helping to regulate the gut microbiota, and may particularly protect against small intestinal bacterial overgrowth (SIBO).28 Several studies also suggest that bile acids activate enteroendocrine cells to release serotonin, which helps promote gut motility.29

Exploring the ins and outs of every type of conjugated and deconjugated bile acid is beyond the scope of this article, and something I’ll hope to cover in a future post. Overall, I do not believe there is sufficient evidence to suggest that the physiologic increase of bile acids seen with a ketogenic diet is harmful to the gut microbiota or gut barrier function.

What about the carnivore diet?

The carnivore diet has recently been touted as a cure-all for a wide variety of diseases. While an all-meat diet might be beneficial as a short-term therapeutic diet and, anecdotally, many people experience improvement in their symptoms, there is limited data on the long-term safety of this dietary approach.

It is theoretically possible to get all of your nutrients from an animal-based diet, assuming that you eat nose-to-tail and consume all parts of the animal. Interestingly, the short-term animal-based diet featured in the study I mentioned above was associated with increased expression of bacterial genes for vitamin biosynthesis.12 As a low residue diet, a reduction in gut inflammation may also improve nutrient status in the short-term. However, we know very little about how the carnivore diet might impact nutrient status, hormones, fertility, and thyroid function in the long-term.

Moreover, there is no evidence that any ancestral population lived on only meat or only plants. Even the Inuit and other populations that lived in the far north went to great lengths to forage plants when they could or boost their fertility in other ways. In his book “Nutrition and Physical Degeneration, A Comparison of Primitive and Modern Diets and Their Effects”, Weston A. Price wrote:

 “Among the Indians in the moose country near the Arctic Circle a larger percentage of the children were born in June than in any other month. This was accomplished, I was told, by both parents eating liberally of the thyroid glands of the male moose as they came down from the high mountain areas for the mating season, at which time the large protuberances carrying the thyroids under the throat were greatly enlarged.”

In other words, these cultures had the traditional wisdom to self-medicate with thyroid glands of other animals to make up for the reduced fertility conferred by their lack of plant foods. Most modern “carnivores” are not doing this, and many are consuming muscle meat alone.

I certainly empathize with those who have found the carnivore diet to provide relief of symptoms. That being said, I believe in most cases, a therapeutic ketogenic diet could be just as effective and that the need to go complete carnivore to relieve symptoms is a sign of an underlying gut infection. Once this is addressed, the ideal diet likely includes some form of plant foods.

Summary & tips for gut health on a ketogenic diet

To summarize, there is no clear evidence that a well-designed high-fat or ketogenic diet is detrimental to the gut microbiota or gut barrier function. In fact, keto-induced changes in the gut microbiota and gut barrier may even be the reason why we see so many benefits from ketosis.

Moreover, we don’t really know what constitutes a healthy gut microbiota, and ketones can replace the short-chain fatty acid butyrate that we typically think of as crucial for gut barrier function. Several case reports indicate that a ketogenic diet may reduce inflammation and improve quality of life in IBS and IBD.

I want to stress that I do not believe that a ketogenic diet is right for everyone. My intention with this article was not to suggest that everyone with a gut issue should try a ketogenic diet. I simply wanted to clear up a lot of the confusion and provide a more complete discussion of the evidence for high-fat diets in relation to gut health.

There are also right and wrong ways to do a ketogenic diet when it comes to gut health. A ketogenic diet high in refined seed oils and processed meats is not going to provide the same therapeutic benefit to the gut as one that includes healthy fats, pastured meats, and lots of non-starchy vegetables.

On that note, here are my top seven tips to doing right by your gut when consuming a high-fat or ketogenic diet:

1) Focus on high-quality fats. I’m talking avocados, avocado oil, olive oil, fatty fish, coconut oil, pastured ghee, butter, tallow, etc. Try to get a mixture of monounsaturated, polyunsaturated, and saturated fat.** Avoid highly processed and refined oils like canola, corn, and soybean oil.

**If you plan to remain on a ketogenic diet long-term, I recommend getting a full cardiovascular profile after you have been on the diet for 1-2 months. A small subset of individuals  (“hyper-responders”) will have an increase in LDL particle number and may need to tweak their fat intake or consider a modified ketogenic diet to ensure they are not increasing cardiovascular risk.

2) Eat your (non-starchy) veggies! Just because you don’t necessarily need the butyrate doesn’t mean you should skimp on vegetables. Try to get a variety of both raw and cooked veggies of all types and colors.

3) Indulge with berries. Berries are a great low-carbohydrate source of prebiotics to support the growth of beneficial microbes.

4) Drink coffee and eat cocoa. Polyphenols promote the growth of beneficial microbes, so consume coffee and cocoa as tolerated. Those with severe gut permeability or autoimmunity may want to avoid these foods initially.

5) Consider nutrient density and eat nose-to-tail. When thinking about the health of our gut and our bodies in general, we should always be sure to be consuming nutrient dense foods like shellfish and organ meats. It’s also important to balance out methionine-rich muscle meats with glycine-rich parts of the animal like cartilage, skin, and bones. One great way to do this is to consume bone broth regularly.

6) Experiment!  The best way to know if keto is healthy for your gut is to try it for 3-4 weeks and see how you feel. Pay particular attention to your energy, skin, mood, productivity, and digestion. Remember, a “healthy” microbiome is simply the microbiome you have when you are healthy!

7) Try “the keto zone”. Unless you’re treating a chronic health condition with therapeutic ketosis, there is no need to be in keto indefinitely. By maintaining a carb range of 20-120 grams (depending on your activity level), you can easily slip out of ketosis to enjoy a few sweet potatoes or plantains and then slip back into ketosis the next day. In fact, this may help your gut and microbes maintain peak metabolic flexibility.

That’s all for now! Be sure to let me know what you thought in the comments below and subscribe to my newsletter so you never miss a post.

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Is a high-fat or ketogenic diet bad for your gut?

BY LUCY MAILING, MD/PHD STUDENT

Ketogenic diets are becoming increasingly popular for everything from weight loss to cancer therapy. Many people have expressed concern about the impact that this has on the health of the gut and the gut microbiome. But does a high-fat diet really spell disaster for the gut? In this article, learn why animal studies are misleading, what the current research says, and why ketosis may even be able to improve gut health in some cases.

If you’ve been reading my blog for a while, you know that I’m a proponent of a low-carb, high-fat or ketogenic diet for many different conditions. Keto is becoming increasingly popular for weight loss, blood sugar regulation, neurodegenerative diseases, and even as a component of cancer treatment. Others, including myself, choose a ketogenic diet for the mental clarity and enhanced productivity.

In recent months, I’ve received a lot of questions as to the effects that this has on the health of the gut and gut microbiome. It seems there is this widespread notion out there that the only thing that feeds beneficial gut microbes is complex carbohydrates, and that if we don’t have butyrate from the fermentation of dietary fiber, our gut barrier suffers, too.

But is this really true? In this article, I’ll dive into the research and provide a complete discussion of the evidence, including what we don’t know.

We don’t really know what constitutes a “healthy” microbiome

New technologies and an increasing interest in gut health in recent years have dramatically increased our understanding of gut microbes, and commercial companies now allow anyone to get a peek at the microbial world that resides in their gut. Unfortunately, the excitement has gotten ahead of the research, and the truth is, we know very little about what constitutes a “healthy” gut microbiota.

Pick any two people, and on average they will only share about a third of their gut microbiota. The other two-thirds of their gut community will vary significantly depending on their genetics, geographical location, history of antibiotic and medication use, mode of birth, diet, and other factors that are likely yet to be discovered. We really don’t have enough information to say that one person’s “two-thirds” is any better than another person’s “two-thirds”, unless one of them has an overgrowth or infection with a known pathogen.

You might say, well, couldn’t we look at microbial diversity? Or stability of the community? While it’s generally believed that diversity and community stability are key components of a healthy gut ecosystem, even these can sometimes be associated with diseased states.1,2 And some of the keystone “beneficial” microbes recognized by many to be crucial for microbiome health, such as Bifidobacterium, are completely absent from the guts of traditional cultures like the Hadza,3 yet these populations are virtually free of chronic disease.

We’ll explore the evolutionary perspective more in the next section.

The gut microbiome has evolved with us – often in the context of periodic ketosis

Our relationship with our gut microbes today is the product of thousands of generations of co-evolution. For millions of years, evolution hasn’t just been acting on our 23,000 human genes, it’s been acting on the nearly 4 million genes (both human and microbial) that are present in and on our bodies.4 We are who we are today because of how we evolved with our microbes.

The environment we evolved in required regular adaptation to changing conditions. Our ancestors did not always have ready access to food and would have undergone occasional bouts of fasting when food was scarce. As such, our bodies have the ability to burn and use carbohydrates when food is plentiful, and to turn dietary fat or stored body fat into ketones for energy when food or carbohydrates are scarce. This is called metabolic flexibility.

So the real question is: Why would our bodies have the metabolic flexibility to deal with the shifting availability of foods – and our gut microbiome not have the same metabolic flexibility? Would our ancestors really have developed a “diseased” microbiome every time starchy carbohydrates became scarce? I think not.

Let’s also consider traditional cultures like the Inuit. Did the Inuit, who ate very few plant foods, really have an unhealthy microbiome? Or did they have a microbiome that was uniquely adapted to their diet? Did they have rampant gut permeability and inflammation from their high-fat diet? Or did their gut also have a form of metabolic flexibility that allowed them to survive on primarily animal protein and fat?

We’ll discuss all of the underlying mechanisms in a moment, but my point here is this: A “healthy” microbiome is simply the microbiome that you have when you’re healthy. And what’s healthy for you may not be healthy for someone else.

This is part of the reason why I always emphasize looking at the overall gut environment and current symptoms when helping clients with gut issues. If someone has low gut microbial diversity but feels fantastic, treating the gut may do more harm than good.

But enough on that – let’s dive into the data.

Animal studies that use a “high-fat diet” are misleading

If you search any database of the scientific literature, you can find over a hundred studies that show feeding animals a “high-fat diet” leads to massive gut dysbiosis, gut permeability, and systemic inflammation. People often cite these studies to suggest that a high-fat diet is also likely to be unhealthy for the human gut microbiome.

Look closer at the methods though, and you’ll see that the “high-fat diet” used in most animal studies is more accurately a diet high in refined soybean oil, lard, and refined sugar, and very low in fiber.5 Dr. Craig Warden, professor at UC Davis, has called this “the mouse equivalent of pork rinds, ribs, and coke,”6 suggesting that this “high-fat diet” is much more reflective of the Standard American Diet than any carefully-crafted ketogenic diet.

Furthermore, human metabolism can easily adapt to a diet higher in fats or carbohydrate. The natural diet of a mouse, on the other hand, is low in fat and high in carbohydrates, so it’s not all that surprising that mice develop issues when eating a diet that is so poorly matched with what they evolved to eat.

Moreover, the strain of mice most commonly used for such studies, the C57Bl/6 mouse, has been genetically selected for its ability to put on weight and raise glucose in response to a “high-fat diet”. While humans tend to show greater weight loss in response to low-carbohydrate diets, C57Bl/6 mice have greater weight gain and metabolic disruptions on low-carb diets. After observing this, principal investigators Dr. Richard Feinman and Dr. Saihan Borghjid concluded:

“The results suggest that rodent models of obesity may be most valuable in the understanding of how metabolic mechanisms can work in ways different from the effect in humans.” 7

In other words, the idea that we can translate any findings in these selectively bred mice fed a “high-fat diet” to health-conscious humans eating a ketogenic diet is just absurd, and a gross misrepresentation of the research.

So, let’s look at the human research instead.

(A ketogenic) diet rapidly and reproducibly alters the human gut microbiome

In 2014, David et al. published a study in the journal Nature where they put healthy human volunteers on a short-term plant-based diet or animal-based diet and demonstrated that distinct gut microbial communities emerged within as little as three days.

This was a pivotal study in microbiome research and one I’ve been aware of for some time (it’s been cited over 2,700 times since 2014), but it wasn’t until I was doing the research for this article and happened to look at the supplementary data that it dawned on me: the animal-based diet was ketogenic!

While the plant-based diet included 300 grams of carbohydrate per day from cereal, vegetables, rice, lentils, and fruit, the animal-based diet included less than 3 grams of carbs per day, with 30% calories from protein and 70% calories from fat coming from eggs, meat, and cheese. This macronutrient ratio is consistent with a ketogenic diet. The researchers even measured ketones in the urine and confirmed that the subjects were in ketosis by day two of the animal-based diet.

In other words – this study is the study that many people are saying we don’t have.

So what did they find? Participants on the animal-based ketogenic diet saw an increase in microbial diversity. They also saw an increase in the relative abundance of bile-tolerant microorganisms like Bilophila, Alistipes, and Bacteroides spp. and a decrease in the relative abundance of microbes known to metabolize complex dietary plant fibers, such as Roseburia, Eubacterium, and Ruminococcus spp. This is not all too surprising.

In line with my evolutionary argument, the authors write:

“Our findings that the human gut microbiome can rapidly switch between herbivorous and carnivorous functional profiles may reflect past selective pressures during human evolution. Consumption of animal foods by our ancestors was likely volatile, depending on season and stochastic foraging success, with readily available plant foods offering a fallback source of calories and nutrients. Microbial communities that could quickly, and appropriately, shift their functional repertoire in response to diet change would have subsequently enhanced human dietary flexibility.”

In other words, our gut microbiota is simply adapting to the current availability of different food sources – it’s not necessarily becoming any more or less pathogenic by the amount of carbohydrate or fat in the diet.

Ketogenic diet-induced changes in the gut microbiome may be protective in multiple sclerosis

What about longer-term studies? One study published in the journal Frontiers in Microbiology in 2017 examined the long-term effects of a ketogenic diet on the fecal microbiota in 25 patients with multiple sclerosis.8

Multiple sclerosis (MS) is an autoimmune disease that affects the nervous system. Like many autoimmune diseases, MS is associated with gut pathologies. In fact, some researchers suspect that gut dysbiosis and intestinal permeability may precede the development of autoimmunity in the first place.9 Thus, it follows that if a ketogenic diet can significantly improve symptoms of MS,10 it’s probably not harming the gut, and may even be improving gut health.

So what did the study find? Patients with MS tended to have reduced Roseburia, Bacteroides, and Faecalibacterium prausnitzii at baseline compared to healthy individuals. They then went on a ketogenic diet for 6 months. The authors write:

“The effects of a ketogenic diet were biphasic. In the short term, bacterial concentrations and diversity were further reduced. They started to recover at week 12 and exceeded significantly the baseline values after 23–24 weeks on the ketogenic diet.” 8

This suggests that, while short-term dietary changes can rapidly shift the composition of the gut microbiota, we may need to look at long-term dietary changes and collect samples at multiple time points to determine the true effect of a dietary intervention.

Unfortunately, this study did not measure symptoms or any other indices of gut health, so we can’t know whether the ketogenic diet was beneficial. To explore whether a ketogenic diet is causally beneficial for the gut microbiome, we’ll have to return to well-designed animal studies.

The gut microbiome mediates the anti-seizure effects of the ketogenic diet

Ketogenic diets are frequently used to treat epilepsy that is unresponsive to drug treatments. While incredibly effective, exactly how the ketogenic diet confers benefits on brain activity remained elusive for decades. However, a new study published in the journal Cell in May 2018 suggests that the beneficial effects of the ketogenic diet are mediated through the gut microbiome!11 In other words, if a ketogenic diet didn’t change the microbiome, it wouldn’t be effective at preventing seizures.

The study was performed in a mouse model of epilepsy (using different strains than the one I mentioned earlier). Like previous studies, they were able to show that feeding the mice a ketogenic diet protected them against seizures. They further demonstrated, however, that treating the mice with broad-spectrum antibiotics abolished the protection against seizures. Similarly, germ-free mice, which are raised in sterile incubators and have no gut microbiome, were not protected against seizures, even when consuming a ketogenic diet.

Interestingly, the ketogenic diet in this study reduced microbial diversity but increased the abundance of Akkermansia muciniphila and Parabacteroides spp. The researchers wondered if these two microbes were responsible for the seizure protection and tried treating mice fed a normal high-carbohydrate chow diet with Akkermansia and Parabacteroides. Amazingly, this conferred protection against the seizures.

Further mechanistic experiments identified a bacterial pathway that elevated the ratio of the inhibitory neurotransmitter GABA relative to the excitatory neurotransmitter glutamate in the brain. GABA calms activity in the brain, so this explains the seizure reduction, and may also explain why many people find the ketogenic diet beneficial for reducing anxiety.

Won’t keto reduce your production of butyrate?

Now that we’ve covered all of the relevant human and animal experimental data that we have to date, I want to talk a bit about the mechanisms involved.

First, we know that fermentable carbohydrates are required for the production of short-chain fatty acids. The short-chain fatty acid butyrate is well-known as the “preferred” fuel source for gut epithelial cells. In most modern humans, it provides about 70 percent of the energy requirements for colon epithelial cells. And we need a regular supply of butyrate to maintain barrier function…right?

Nope. Turns out that there are several other molecules that can perform many of the signaling functions of butyrate AND serve as a source of fuel for the gut epithelial cells! In fact, this idea of a “preferred” fuel source may be skewed from studying people (and rodents) who are eating large amounts of carbohydrates. Butyrate production will undoubtedly be reduced on a ketogenic diet, but other molecules can take its place to help maintain gut barrier function.

Ketone bodies and isobutyrate can replace butyrate

There are three molecules that can replace butyrate: isobutyrate, acetoacetate and beta-hydroxybutyrate.

Isobutyrate is a metabolite of protein fermentation that is typically produced in much lower levels than butyrate. When butyrate is absent, isobutyrate can be taken up by from the gut lumen by gut epithelial cells and metabolized for energy. Isobutyrate was found to be elevated in the study I mentioned above in those consuming the animal-based ketogenic diet.12

Moreover, isobutyrate can stimulate the same receptors as butyrate in the gut (GPR41, GPR43, and GPR109a) that lead to mucus secretion, antimicrobial peptide release, and immune regulation.13 And while isobutyrate may be produced at lower levels on a moderate-high-protein diet than butyrate would be produced on a high-carbohydrate diet,12 isobutyrate has been shown to be a more potent stimulator of GPR41 (FFAR3), one of the primary receptors for butyrate, than butyrate itself!14 In other words, what isobutyrate lacks in concentration, it may make up for in potency.

The other two molecules, acetoacetate and beta-hydroxybutyrate (βHB), are the two major ketone bodies produced by the liver during a ketogenic state. Like butyrate, βHB can also stimulate GPR109a, reducing intestinal inflammation. Most notably, however, both βHB and acetoacetate are intermediates in the pathway for butyrate metabolism. In other words, when butyrate is taken up by gut epithelial cells, it is actually converted into βHB first, and then acetoacetate, before being broken down further for energy. See the figure below:

Now, cutting out three steps of metabolism doesn’t seem like a big deal, until you realize that hydrogen sulfide (H2S) impairs the enzyme that catalyzes the first step of butyrate oxidation,15 and many individuals with gut dysbiosis have excess production of this toxic gas.

Getting your substrates from the blood also doesn’t seem to have much of an advantage, until you consider that many people with inflamed guts have mucosal damage where butyrate uptake is impaired.

So what does this mean? If you’re generally healthy and have a healthy gut, butyrate is well equipped to deal with all your gut’s needs, no ketones needed.

However, if you:

  • have ulcerative colitis or other mucosal damage, where butyrate uptake is impaired,
  • have high levels of hydrogen-sulfide producing organisms, where the first step of butyrate oxidation is impaired (prevalent in those with IBS-D),
  • have gut dysbiosis characterized by a lack of butyrate-producers, or
  • have carbohydrate malabsorption and are on long-term low-FODMAP or SCD, resulting in reduced butyrate production,

it may be wise to try therapeutic ketosis to support gut epithelial cell metabolism, at least until treating the underlying gut pathologies and healing the gut lining.

Unfortunately, few studies have been performed on ketogenic diets for Crohn’s disease, ulcerative colitis, or irritable bowel syndrome. One case report found that a paleolithic, ketogenic diet induced complete remission in a young boy with severe Crohn’s disease.16 A second case report found that a low carbohydrate diet with ketone ester supplementation significantly reduced inflammation and improved quality of life in a patient with Crohn’s disease.17

Another study of 13 patients with diarrhea-predominant irritable bowel syndrome (IBS-D) found that 10 reported relief of symptoms during a 4-week ketogenic diet.18 Anecdotally, many people with ulcerative colitis have found relief from ketogenic diets, including popular health blogger and biochemist Robb Wolf.

To my knowledge, no studies have assessed the effects of ketones or a ketogenic diet on gut barrier function. This is certainly something I hope to study in my lab in the future.

But don’t high-fat diets increase LPS absorption?

Another common argument for avoiding high-fat diets is that they increase intestinal absorption of lipopolysaccharide (LPS), a molecule found in the cell walls of gram-negative bacteria. If LPS gets into circulation, it can cause low-grade, systemic inflammation.

To really understand this mechanism, we need to review how fats are digested and absorbed. When we eat fat, specialized cells in the small intestine release a hormone called cholecystokinin (CCK). CCK stimulates the gallbladder to secrete bile into the small intestine. Here, the bile acids surround fat molecules, helping to make them water soluble (much like dish detergent helps to emulsify oil).

It turns out that LPS has a high affinity for these water-soluble packages, called micelles. Micelles eventually diffuse toward the gut epithelium, where their contents (including LPS) are picked up by gut epithelial cells. The epithelial cells repackage the lipids and LPS into chylomicrons, which can then be exported to the liver via the lymphatics.

When we consume more long chain fatty acids, our body makes more of these chylomicrons, so more LPS can hitch a ride in this fashion.19 Indeed, fat-enriched meals have been shown to moderately increase serum levels of LPS in both mice and humans.20,21 While this is absolutely a real phenomenon and worth considering, I believe this is generally a non-issue for several reasons.

First, several studies suggest that the transport of LPS by chylomicrons may confer an advantage because it favors clearance of LPS by the liver, reducing the toxicity of LPS.22,23 Moreover, chylomicrons also have an innate ability to inactivate LPS.24 Altogether, the increased absorption of LPS appears to reduce inflammation in the gut mucosa.25

This is especially important since the primary mode of systemic exposure to LPS is not through fat absorption, but through a leaky gut! When the gut is permeable, large amounts of LPS can leak into the submucosa and bloodstream, causing localized gut immune responses and systemic inflammation.

Compared to full-blown intestinal permeability, chylomicron-induced LPS absorption is merely a drop in the bucket. (In fact, for those who are dealing with severe intestinal permeability, chylomicron-induced detoxification of LPS may even reduce inflammation enough to facilitate healing of the gut epithelium.)

Furthermore, if fat-induced LPS absorption was an issue, we would expect to see increased systemic inflammation in those fed a high-fat ketogenic diet. On the contrary, subjects fed ketogenic diets almost universally experience a reduction in systemic inflammation.26

Alright so, hopefully by this point, I’ve convinced you that high-fat diets are not to be feared for their lack of butyrate or increased absorption of LPS. In the next section, we’ll see how bile acids might also contribute to a healthier gut.

Bile acids are critical for gut health

Some people have also suggested that a high-fat diet might be detrimental to the gut microbiota and gut barrier because it stimulates increased secretion of bile acids. The more fat you eat, the more bile is released into the small intestine.

Indeed, some studies have shown that sustained exposure of the gut barrier to high concentrations of bile acids results in intestinal permeability. However, physiologic doses of bile acids have been shown to support barrier function, inducing the secretion of mucus from goblet cells, promoting epithelial cell migration, and boosting gut innate immune defenses.27

Bile acids also have antimicrobial properties, helping to regulate the gut microbiota, and may particularly protect against small intestinal bacterial overgrowth (SIBO).28 Several studies also suggest that bile acids activate enteroendocrine cells to release serotonin, which helps promote gut motility.29

Exploring the ins and outs of every type of conjugated and deconjugated bile acid is beyond the scope of this article, and something I’ll hope to cover in a future post. Overall, I do not believe there is sufficient evidence to suggest that the physiologic increase of bile acids seen with a ketogenic diet is harmful to the gut microbiota or gut barrier function.

What about the carnivore diet?

The carnivore diet has recently been touted as a cure-all for a wide variety of diseases. While an all-meat diet might be beneficial as a short-term therapeutic diet and, anecdotally, many people experience improvement in their symptoms, there is limited data on the long-term safety of this dietary approach.

It is theoretically possible to get all of your nutrients from an animal-based diet, assuming that you eat nose-to-tail and consume all parts of the animal. Interestingly, the short-term animal-based diet featured in the study I mentioned above was associated with increased expression of bacterial genes for vitamin biosynthesis.12 As a low residue diet, a reduction in gut inflammation may also improve nutrient status in the short-term. However, we know very little about how the carnivore diet might impact nutrient status, hormones, fertility, and thyroid function in the long-term.

Moreover, there is no evidence that any ancestral population lived on only meat or only plants. Even the Inuit and other populations that lived in the far north went to great lengths to forage plants when they could or boost their fertility in other ways. In his book “Nutrition and Physical Degeneration, A Comparison of Primitive and Modern Diets and Their Effects”, Weston A. Price wrote:

 “Among the Indians in the moose country near the Arctic Circle a larger percentage of the children were born in June than in any other month. This was accomplished, I was told, by both parents eating liberally of the thyroid glands of the male moose as they came down from the high mountain areas for the mating season, at which time the large protuberances carrying the thyroids under the throat were greatly enlarged.”

In other words, these cultures had the traditional wisdom to self-medicate with thyroid glands of other animals to make up for the reduced fertility conferred by their lack of plant foods. Most modern “carnivores” are not doing this, and many are consuming muscle meat alone.

I certainly empathize with those who have found the carnivore diet to provide relief of symptoms. That being said, I believe in most cases, a therapeutic ketogenic diet could be just as effective and that the need to go complete carnivore to relieve symptoms is a sign of an underlying gut infection. Once this is addressed, the ideal diet likely includes some form of plant foods.

Summary & tips for gut health on a ketogenic diet

To summarize, there is no clear evidence that a well-designed high-fat or ketogenic diet is detrimental to the gut microbiota or gut barrier function. In fact, keto-induced changes in the gut microbiota and gut barrier may even be the reason why we see so many benefits from ketosis.

Moreover, we don’t really know what constitutes a healthy gut microbiota, and ketones can replace the short-chain fatty acid butyrate that we typically think of as crucial for gut barrier function. Several case reports indicate that a ketogenic diet may reduce inflammation and improve quality of life in IBS and IBD.

I want to stress that I do not believe that a ketogenic diet is right for everyone. My intention with this article was not to suggest that everyone with a gut issue should try a ketogenic diet. I simply wanted to clear up a lot of the confusion and provide a more complete discussion of the evidence for high-fat diets in relation to gut health.

There are also right and wrong ways to do a ketogenic diet when it comes to gut health. A ketogenic diet high in refined seed oils and processed meats is not going to provide the same therapeutic benefit to the gut as one that includes healthy fats, pastured meats, and lots of non-starchy vegetables.

On that note, here are my top seven tips to doing right by your gut when consuming a high-fat or ketogenic diet:

1) Focus on high-quality fats. I’m talking avocados, avocado oil, olive oil, fatty fish, coconut oil, pastured ghee, butter, tallow, etc. Try to get a mixture of monounsaturated, polyunsaturated, and saturated fat.** Avoid highly processed and refined oils like canola, corn, and soybean oil.

**If you plan to remain on a ketogenic diet long-term, I recommend getting a full cardiovascular profile after you have been on the diet for 1-2 months. A small subset of individuals  (“hyper-responders”) will have an increase in LDL particle number and may need to tweak their fat intake or consider a modified ketogenic diet to ensure they are not increasing cardiovascular risk.

2) Eat your (non-starchy) veggies! Just because you don’t necessarily need the butyrate doesn’t mean you should skimp on vegetables. Try to get a variety of both raw and cooked veggies of all types and colors.

3) Indulge with berries. Berries are a great low-carbohydrate source of prebiotics to support the growth of beneficial microbes.

4) Drink coffee and eat cocoa. Polyphenols promote the growth of beneficial microbes, so consume coffee and cocoa as tolerated. Those with severe gut permeability or autoimmunity may want to avoid these foods initially.

5) Consider nutrient density and eat nose-to-tail. When thinking about the health of our gut and our bodies in general, we should always be sure to be consuming nutrient dense foods like shellfish and organ meats. It’s also important to balance out methionine-rich muscle meats with glycine-rich parts of the animal like cartilage, skin, and bones. One great way to do this is to consume bone broth regularly.

6) Experiment!  The best way to know if keto is healthy for your gut is to try it for 3-4 weeks and see how you feel. Pay particular attention to your energy, skin, mood, productivity, and digestion. Remember, a “healthy” microbiome is simply the microbiome you have when you are healthy!

7) Try “the keto zone”. Unless you’re treating a chronic health condition with therapeutic ketosis, there is no need to be in keto indefinitely. By maintaining a carb range of 20-120 grams (depending on your activity level), you can easily slip out of ketosis to enjoy a few sweet potatoes or plantains and then slip back into ketosis the next day. In fact, this may help your gut and microbes maintain peak metabolic flexibility.

That’s all for now! Be sure to let me know what you thought in the comments below and subscribe to my newsletter so you never miss a post.

  1. Jiang, H. et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav. Immun. 48, 186–194 (2015).
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  8. Swidsinski, A. et al. Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet. Front Microbiol 8, 1141 (2017).
  9. Fasano, A. & Shea-Donohue, T. Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nature Reviews Gastroenterology & Hepatology 2, 416–422 (2005).
  10. Storoni, M. & Plant, G. T. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Multiple Sclerosis International (2015). doi:10.1155/2015/681289
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By |2018-10-18T00:17:06+00:00October 16th, 2018|

6 Comments

  1. Alyssa October 16, 2018 at 8:10 pm - Reply

    Lucy, I’m so glad I met you at AHS and started following your blog! I gotta say, you’re one of the few independent researchers/bloggers I’ve encountered who I trust completely to be thorough and objective when looking at and summarizing the research. So much fascinating stuff in this article! Thank you so much!

    • Lucy Mailing October 18, 2018 at 12:27 am - Reply

      Thanks so much for your kind words, Alyssa! I always strive to be as objective and evidence-based as possible, so it’s nice to know that it comes through 🙂 Thankful that we met at AHS as well!

  2. David October 17, 2018 at 2:23 am - Reply

    So a high fat diet increases bile production, and bile-eating bacteria increase. The bile eating bacteria (bilophila, desulfovibrio) produce hydrogen sulphide.

    Now being in ketosis means that the H2S interfering with butyrate conversion is not a problem. However, iirc H2S is toxic in other ways, such as killing some epithelial cells. It is also associated with higher levels of colon cancer.

    So does ketosis imply always having high levels of H2S, and what about these other consequences of those high levels? Is it possible to – or do you even want to – cut the numbers of H2S bacteria?

    • David October 17, 2018 at 2:26 am - Reply

      And another thing….

      “several studies suggest that the transport of LPS by chylomicrons may confer an advantage because it favors clearance of LPS by the liver”

      What happens if the liver is not working all that well? I suppose the liver is needed for non-ketogenic diets as well, so it may be six of one and half-a-dozen of the other.

      • Lucy Mailing October 18, 2018 at 12:29 am - Reply

        Yep, I think you hit the nail on the head! If the liver is not functioning wlel and you have leaky gut, you’ll have a tough time regardless of what diet you’re eating. In that case, it would be best to provide some nutritional support for the liver while working to bring down inflammation in the gut.

    • Lucy Mailing October 18, 2018 at 12:20 am - Reply

      Thanks for the insightful questions, David! I agree that animal-based or ketogenic diets seem to increase the relative abundance of Bilophila and other microbes that are known to reduce sulfite to hydrogen sulfide.

      However, this does not tell us if production of the hydrogen sulfide gas is present or not. The study I referenced above (David et al. 2014) did find an increase in Bilophila and the genetic capacity for H2S production, but did not measure actual H2S output. We see many such instances in microbiome research where the metabolic capacity of the gut microbiome does not actually reflect the metabolic output, so I don’t think it’s sufficient to make any firm conclusions.

      Additionally, increasing evidence suggests that physiological amounts of H2S are actually beneficial, inhibiting free radical reactions and oxidative stress. https://mcb.asm.org/content/33/6/1104

      I’m certainly open to the idea that in some individuals, a ketogenic diet could increase H2S production. However, the only study to date of a ketogenic diet in IBS patients found that 10 of 13 patients with diarrhea-predominant IBS found significant relief of symptoms. And excess H2S tends to be prevalent in those with IBS-D.

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