Low carb diet and the microbiome: What you need to know

Low carb diets are becoming increasingly popular due to their effectiveness for weight loss. Though they’ve been around for while, concerns over their long term effects prevented health authorities and physicians from recommending them.

Even if there are long term concerns with low carbohydrate diets, being overweight or obese likely causes much larger problems. As a result, more and more health practitioners and organizations green light low carbohydrate diets.

One concern with these diets involves the microbiome. Low carb diets tend to also be low fiber, and fiber is considered healthy for the microbiome. Therefore, it must be essential for a healthy gut, right?

A recent review discusses how this may not be the case, that our microbiome is flexible enough to compensate for a lack of microbiota accessible carbohydrate. Furthermore, one may be able to develop a diet that swaps out fiber for protein and get similar results.

However, individual differences likely drive the suitability of these diets. That is to say, a low carb diet may be great for one person, and terrible for another.

In this week’s blog we’ll briefly discuss some aspects of this review as well as some gaps not addressed. We’ll also discuss how to determine if your low carb diet is working for your gut.

We highly recommend reading this review as it covers many important topics not discussed here. The full text is freely available at the link provided.

Low carb diet meal

Low carb diets and metabolic flexibility of the human microbiome

Science behind the microbiome is in it’s relative infancy. Based on the trajectory of the research, there is a tremendous bias towards higher fiber diets. Consequently, there is an assumption that low fiber diets are bad for the microbiome.

With this in mind, a new review titled Reframing Nutritional Microbiota Studies To Reflect an Inherent Metabolic Flexibility of the Human Gut: a Narrative Review Focusing on High-Fat Diets tackles this bias.

At the heart of the matter is that since we don’t digest or absorb fiber, it makes it into our colon intact. The vast majority of our gut microbiome, ~95%, is in the colon.

When fibers enters the colon, our microbes ferment it into short chain fatty acids, which have numerous effects in the gut and beyond. One of these short chain fatty acids is butyrate. Butyrate is highly beneficial to colon health as it is the primary fuel source of colonocytes, cells that make up the colon.

In this review, they argue that there are other metabolic pathways to butyrate generation. For example, microbes ferment specific amino acids into butyrate.

On top of this, a separate branched, short chain fatty acid called isobutyrate may substitute for butyrate, as can the ketone beta-hydroxybutyrate. So we may be able to formulate a low carb/low fiber diet that gets around the hypothesized negative effects of a low fiber diet.

Though, to be clear, it’s not certain that both or either can fully re-capitulate all of the effects of butyrate.

Human equivalent to a rodent high fat diet

Negative effects of a “high fat diet”

Generally speaking, low carb diets tend to be higher in fat. Historically, we’ve been programmed to avoid fat. Twenty years ago, it would be considered madness to follow a high fat diet for health. But the data is clear that, in a calorie restricted state, this is probably an unfounded fear.

On the other hand, microbiome research shows that “high fat diets” are bad for the microbiome. In addition to increasing inflammation, these diets also thin out the mucus layer, increase intestinal permeability, and generate metabolites that increase colon cancer risk.

As stated in this review, “high fat diet” is a misnomer. The “high fat diet” used in microbiome research is also high in sugar, low in fiber, and is more consistent with a junk food.

A better way to refer to these diets is a junk food diet. Think burgers, fries, chips, and cookies. They in no way look like a ketogenic or low carbohydrate diet.

Therefore, the negative effects of these diets are not necessarily due to their fat content.

Poo-pooing the negative effects of an animal-based diet on health

A large body of epidemiological evidence points to a general negative effect of high meat consumption on health outcomes, particularly red meat. This includes colorectal cancer, cardiovascular disease, obesity, and type 2 diabetes.

The theoretical mechanisms behind the negative effects of an animal-based diet on health include increased absorption of lipopolysaccharide(LPS), increased TMAO production by the microbiome, increased secondary bile acids, and increased heme iron intake.

The review covers each of these mechanisms in much greater detail.

Increased LPS absorption

LPS is a component of the cell wall of gram-negative bacteria that live in our gut. When LPS enters the circulation, it initiates an inflammatory response. When we consume fat, absorption is dependent on transporters called chylomicrons, that also carry LPS into the circulation.

Fortunately, this entire process occurs in the small intestine, where bacterial populations are quite small. It also enters the lymphatic system where it can be acted on by alkaline phosphatase.

Outside of obese individuals or ultra-high calorie diets, this is likely not a major source of LPS in the circulation. Increased permeability in the colon is likely a bigger driver of systemic LPS due to much higher bacterial humbers. This may be more driven by hyperglycemia.

This is important to keep in mind if you are following a long term ketogenic diet and decide on a whim that now is the time for pie. You will absolutely experience hyperglycemia doing that.

Increased microbial generation of trimethylamine-N-oxide(TMAO)

TMAO is a newly discovered biomarker possibly related to an increased risk of cardiovascular disease. The theory behind it is that high intake of animal products increase TMAO by supplying microbes with its precursors carnitine and choline.

However, it is way too soon to determine what that means. An increase in TMAO may simply be a biomarker of dysbiosis via an elevated level of bacteria that produce it, or a depressed level of bacteria that metabolize it.

Furthermore, fish have high levels of TMAO and fish intake is protective of cardiovascular disease. In addition, a Mendelian randomization study found that type 2 diabetes and chronic kidney disease cause elevated TMAO levels.

Thus, TMAO may be related to CVD as a marker for metabolic health, and not as a marker of meat intake.

Increased secondary bile acid production

When we consume fat, the gallbladder releases bile acids into the duodenum. This emulsifies fats, improving their digestion. While the small intestine recycles 95% of these primary bile acids, 5% slip into the colon.

In the colon, bacteria convert these primary bile acids into secondary bile acids. In general, a high load of secondary bile acids is considered bad. But it’s important to point out that secondary bile acids have important signaling properties.

Therefore, we can’t assume that elevated levels are necessarily bad. We simply don’t know the significance.

Increased heme iron intake

Of the concerns covered in this review, they completely brushed aside heme iron. The one mention was simply:

“…the relevance of heme iron remains to be seen.”

Dietary iron comes in two forms: heme and non-heme iron. Animal products contain heme iron, while plant products contain non-heme iron.

Heme iron is problematic because it’s a pro-oxidant and highly bioavailable compared to non-heme iron. As a result, high intake of animal products may lead to excess heme iron.

A review published in 2020 but not covered by this review builds a pretty strong case for the problems with high heme iron intake. Included in the review were a couple of human studies showing issues with high heme iron intake:

Previous evidence concludes that there is a dose-response to red meat intake and the fecal lipid peroxidation marker ATNC at normal meat intakes (~1/4, ~1/2, and 1lb/day). Consuming 1lb/day increased ATNC to an equivalent extent as smoking increases tobacco-specific NOCs. But, again, we don’t know the significance of this.

It’s important to point out that this is specific to red meat, which is a higher source of heme iron than other types of meat.

Ammonia

Missing from this conversation entirely is ammonia. Dietary protein is the only macronutrient that contains nitrogen, which bacteria(and we) use to generate ammonia(NH3). As such, increased protein intake increases ammonia in the breath and blood as well as fecal ammonia.

Ammonia causes DNA damage and inhibits butyrate oxidation by colonocytes(This may be why fecal butyrate levels were comparable between the animal-based and plant-based diets discussed in this review). Futhermore, ammonia increases the pH in the colon and increases inflammation, further inhibiting butyrate transport in to colonocytes.

While there may be shifts in the microbiome that deal with this, it’s a potentially significant problem.

Hydrogen sulfide: An important consideration

It was nice to see hydrogen sulfide(H2S) mentioned in this review as a cautionary tale. H2S is something normally ignored by proponents of animal-based diets. Sulfate-reducing bacteria(SRB) generate hydrogen sulfide in the colon, which is largely dictated by access to dietary sulfur.

When most people think of dietary sulfur, their first thought is cruciferous vegetables. However, dietary intake of sulfur-based amino acids(cysteine, methionine, and taurine) is by far the greatest source of sulfur in the diet.

At lower levels, hydrogen sulfide has numerous beneficial effects throughout the body. Unfortunately, at higher doses, hydrogen sulfide is toxic. So much so that mitochondria in colonocytes prioritize H2S detoxification when it’s high by inhibiting butyrate oxidation. As you can imagine, this can be problematic.

In addition to dietary protein, dietary fat intake also increases SRB in the colon by increasing taurine-conjugated bile acids. Those with high SRB in their gut, which include multiple Desulfovibrio species, Fusobacterium nucleatum, and Bilophila wadsworthia, should tread with caution.

Though increasing animal protein and fat, in general, will increase their prevalence if you have them.

High protein intake in a low carb diet

As you can see many of the issues in a low carb diet stem from excessive protein intake. This is sort of a catch-22, because adequate protein intake is important for maintaining muscle mass as you age and increasing satiety.

Most well-formulated keto diets restrict protein enough for this to not be a problem. The only diet of concern would be a strictly followed Carnivore diet.

It’s important to point out that this issue is not dependent specifically on how much protein you eat. Rather, it’s dependent on how many, and likely which, amino acids reach the colon.

Fortunately, we may be able to work around this issue by eating specific foods that contain the proper amino acid make up. We’ll drop that list on social media later this week, so don’t forget to follow us at the links below.

Is a low carb diet right for you?

Mechanisms and science are great, but how do you decide if a low carb diet is right for you? Probably the most important impact of diet on overall health depends on one thing: Calorie restriction.

“Calorie restriction is a strong environmental force that alters the gut microbiota and global metabolome.” For many people, a low carb diet leads to calorie restriction without the nuisance of having to count calories. This is likely due to increased satiety and reduced consumption of junk and highly processed foods.

It’s important to point out that when we say calorie restriction, we’re simply referring to a daily calorie intake that leads the individual to maintain a healthy weight.

For most people, this corresponds to a BMI of 18.5-24.9kg/m2, here’s a calculator you can use to determine yours. Though if you’re a bodybuilder or genetic muscle freak and carry a large amount of lean mass, BMI isn’t a great measure.

Another consideration is your ability to stick to a low carb diet, especially at the very low end, as in a ketogenic diet. Going off the deep end and crushing donuts on a semi-regular basis is a recipe for hyperglycemia.

This is what always got me into trouble. If I started a ketogenic diet today, in a month I’d drop 10lbs. But it’s 10lbs I don’t need to lose(I’m currently 180lbs, which puts me at a BMI of 25.1). Additionally, I like carbs and am insulin sensitive enough to eat 300-400g of them per day and maintain an A1c of 4.8%, so I enjoy them.

Yes, I know A1c isn’t a great measure for blood glucose in some people. But mine has been as high as 5.7% when I was unhealthy, and I crush an oral glucose tolerance test.

Furthermore, I’m not convinced postprandial glucose excursions are that important in a lean, metabolically healthy individual.

Gut health implications of a low carb diet

But how do you determine if a low carb diet is ok for your gut? If you’re hoping for some sort of highly technical test to determine this, you’ll be sorely disappointed. It would be great to be able to use some of the common stool tests such as GI maps or GI360.

The problem is, these tests don’t have great diagnostic value because they haven’t been validated for those purposes. That said, a good practitioner may be able to offer some insights, but it’s still a guessing game.

Regardless, from a gut standpoint, it’s probably more important to go by how you feel from a digestion standpoint.

  • Do you make #2 at least once every 2-3 days?
  • Are you a type 3 or 4 on the Bristol Stool Chart?
  • Do you pass stools easily, without straining?
  • Are they brown?

If you hit yes on all factors, I wouldn’t worry too much about how a low carb diet affects your gut. This doesn’t mean that you’re free and clear from problems later on down the road such as colon cancer.

If that’s a concern for you, you could always try a plant-based low carbohydrate diet or include some higher fiber foods. If that’s something you can’t or don’t want to do, next week we’ll be dropping that handy little list of animal-based foods that the microbiome uses to generate butyrate. So follow us on Facebook, Instagram, and Twitter to get the deets!

As always, you should discuss changes like this with your doctor.

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