Disclaimer: It’s important to realize, despite what you read everywhere, what we know about the microbiome isn’t that substantial. We don’t know that changing the microbiome improves health, we just know that when bad health pops up there are distinct differences in the microbiome. A “bad” microbiome could lead to bad health, or bad health could lead to a “bad” microbiome. In fact, we don’t even know what a “bad” microbiome is, if there is even such a thing. It seems that this is variable depending on the environment you live in, but certain things such as low diversity seem to be bad. Finally, while Ubiome testing is interesting, we don’t know that the bacteria in your feces represents the bacteria in your gut accurately. Given this info and that the sample size is 1, I ‘m not making any hard scientific claims.
Research in to the microbiome, the trillions of bacteria that inhabit your gut, has exploded over the last decade. Your commensal bacteria do many things for you. Things such as:
- Nutrient synthesis and digestion
- Regulation of the intestinal barrier
- Modulation of the immune system
- Regulation of appetite
- Regulation of metabolism
- And more
As research on the microbiome explodes, so do the cottage industries surrounding it. This includes companies selling probiotics, prebiotics, and a host of other products to improve GI health.
While I think some of these products are good and may provide some benefit, we aren’t there yet. The truth is, we only know that the microbiome is associated with a bunch of negative health outcomes, not that it causes them.
My personal opinion is that some of the things going on in the microbiome cause problems and vice versa. Once the internal machinery changes, so does the microbiome.
This opens up something important. The notion that changing your microbiome has beneficial effects isn’t out in left field. Yet, the current focus on what’s important to do so is.
Taking probiotics or prebiotics to populate your gut with bacteria isn’t an effective strategy. It’s also not scientific at all.
Taken from: http://www.frontdoorfitness.com/wp-content/uploads/2016/07/Foods-for-gut-health-1.jpg
Food availability is only one environmental condition
One of the primary methods of modulating the microbiome is diet. It makes sense. Bacteria that live in your digestive tract get exposed to the nutrients you put through it. But, this view is entirely too myopic. The type of food your microbiome gets exposed to is a worthy environmental condition. It’s just not the only one.
A great example is how beer is made. If I take yeast and mix it with grains on a plate nothing happens. If I grind grains, put them in a brew kettle with hot water and hops for a while, and then add yeast I’ll have the beginnings of beer.
Without grinding the grains, heating them up, and adding water, what I have will never make beer. These are important environmental conditions that must exist for yeast to make beer.
Even if I meet all these conditions and put the beer in the fermenter, things can still go wrong. Yeast are active at specific temperatures. If I take yeast that’s more active at a colder temperature and let it ferment in a warm room, this will change what I get in the end. Light can also be problematic as it will affect the hops.
The point of this beer discussion is that only focusing on food that bacteria consume in your gut is a terrible approach to modulating the microbiome. Even if I ground the grain and mixed it with the yeast it still needs water.
For beer, water is an environmental condition that must be present for the yeast to proliferate. There are numerous factors in the gut other than food that regulate the microbiome as well.
Taken from: http://pharmrev.aspetjournals.org/content/pharmrev/66/4/948/F9.large.jpg
Environmental conditions in the gut other than food
In your gut, there are some major environmental factors that determine what populates it. This includes pH, oxygen levels, digestive enzymes, and components of the enterohepatic circulation. Some microbes are even dependent on byproducts of the metabolism of other microbes. All these factors have dramatic effects on the GI environment.
For example, in a healthy person with good bile flow, bacteria in the small intestine must be bile resistant. Lactobacillus and Bifidobacteria are 2 genera of commensal bacteria found in the human small intestine. Both have multiple traits contributing to bile resistance(1). Even so, bile induces other mechanisms in the ileum that keep even bile resistant bacteria out of it.
Bile resistance gives commensals a competitive advantage over bacteria that compete for the same resources everywhere else in the small intestine. If other bacterial species with the same food needs outpace commensals, it’s not food availability that’s the problem. It’s a lack of bile or a change in another environmental factor.
Even if the food availability changes, bile produces strong selective pressure. Bile has direct antimicrobial effects that disrupt cell membranes. It also causes the release of antimicrobial peptides in the ileum. This prevents bacterial overgrowth there, an important factor in preventing SIBO in the ileum.
Strains of bacteria that colonize the upper digestive tract must be resistant to bile. If you stop making it or it isn’t made properly, then it’s anyone’s game.
Bile has other effects that are beneficial in people with SIBO. People with SIBO are often categorized as either methane- or hydrogen-dominant. Hydrogen produced in the gut enters one of 3 pathways based on the proportions of bacteria there. Hydrogen gets used by bacteria to create either methane, acetate, or hydrogen sulfide.
Bile blocks methane production by bacteria in the gut(2). This routes excess hydrogen to the acetate and hydrogen sulfide pathways. Of course, bacteria with these pathways must be present.
Bile is simply another environmental factor in the gut ripe for manipulation. It’s also an important one that’s completely neglected.
Ideally, we want to provide food for the good guys. But we must also optimize environmental conditions in the gut to take advantage of the inherited traits that give commensals an advantage over pathogenic bacteria.
When they say our microbiome evolved with us, this is what they mean. The microbiome in the upper digestive tract would look vastly different than it does now if we hadn’t been producing bile this whole time.
Enter the N=1 experiment
Back in November I knew I had to do a week of doxycycline. I planned to perform a test using Ubiome to see what an antibiotic would do to my microbiome. I would test
- Before antibiotics
- On my last day of antibiotics
- 2 weeks after antibiotics
- 6 weeks after antibiotics
- 12 weeks after antibiotics
I also planned to take the standard approach to preventing devastation by antibiotics to my microbiome. This included taking probiotics and a prebiotic fiber blend.
For my probiotic, I used Megasporebiotic. Megaspore is primarily multi-strain bacillus spores that survive the acidic environment of the stomach. For prebiotics, I took a homemade fiber blend. This blend included:
- Acacia fiber
- Inulin
- Larch arabinogalactin
- Glucomannan
- Amazing Grace High Orac Green Superfood
The dosage was 5g of this mix 1x/day with lunch. I hoped to change or at least maintain my microbiome with my standard diet. I also didn’t want to go crazy on the supplemental fiber.
My diet was clean during the week. It included lots of veggies, moderate amounts of fat and protein, and little to no processed food. On the weekends I didn’t restrict what I ate and drank craft beer Friday-Sunday. Here is a sample weekday for me:
- First meal at noon: 2 eggs, 2 slices of bacon, (1 sweet potato, 1/2 large onion,3 cloves of garlic sauteed in grassfed ghee), 1 Thomas high fiber english muffin w/ghee, 1 banana
- Second meal around 3pm: Salad=(1 can of anchovies, 1 serving raw grassfed cheese, 2-3 cups super green blend, 1 serving cherry tomatoes, 2 pickle spears, 8 olives, 4 baby bella mushrooms, olive oil/vinegar), 1/2 cup of wild blueberries, 1/2 cup raspberries, 2 tbsp peanut butter, , 5g supplemental fiber
- Last meal around 7pm: 1/4-1/2lbs ground turkey sausage w/2-3 servings of Wegmans Frozen Organic Stir Fry Blend sauteed in coconut oil, roasted fingerling potatoes
This layout was pretty consistent during the week and is to this day. I also rotate meats and veggies for each meal. As you can tell, I also fast 12-16 hours every day from my last meal to my first.
My exercise includes strength training 2-3 times per week and cardiovascular exercise 5 times per week. I aim for a heat rate between 140-150bpm during cardio. (Cardiovascular exercise plays a pretty major role as I’ll describe later). I also average about 15k steps per day everyday.
For disclosure sake, I don’t smoke and get between 7-8hours of sleep every night. I also took all stool samples on a Friday first thing in the morning. My meals on Thursdays were not identical from test to test, but they followed the structure of meals posted above.
My protocol for testing was consistent across samples taken. I’d wake up, take the kit to the bathroom, and open it. I was always careful to not touch any of the test supplies to anything.
I’d make my movement and before wiping would pull the first layer of toilet paper off of the roll and throw it in the toilet. This is to ensure that any bacteria that may find their way on to the roll isn’t on what I wipe my backside with.
Next, I’d wipe with the fresh TP and swab it with the swab provided and dip it in to the test solution. After shaking it vigorously for a minute or 2 I put it in the envelope and sent it on its way.
Initial Ubiome results
My first Ubiome test compared to the average of all other samples was pretty telling.
- I had terrible diversity(3rd percentile)
- Only 50% Bifidobacteria
- A Firmicutes:Bacteroidetes ratio of 4.9:1.
My second test wasn’t sampled properly so there’s no data. In the 3rd and 4th tests there were no significant changes aside from a change in the Firmictues:Bacteroidetes ratio, shooting up to 7.9:1.
It makes sense that this ratio rose since I was taking supplemental fiber. Many plant fermenters belong to the Firmicutes phylum. To rise that much seems pretty extreme given that the fiber difference was only 5g/day.
I’m guessing that, even in the absence of fiber, I just tend to house more Firmicutes and far fewer Bacteroidetes. My baseline test in the absence of fiber seems to tell this story.
As you can see, my Firmicutes started 28% above “normal” and my Bacteroidetes started 47% below “normal”. This is compared to “All Samples”, or anyone who has had their microbiome sampled by Ubiome.
I suspect this may be due to my upbringing of a C-section birth, formula feeding, and rampant antibiotic use in my youth. But that’s just a hunch.
What’s with all the Firmicutes?
Digging a little deeper in to my results, the high Firmicutes:Bacteroidetes ratio may be a consequence of rampant antibiotic use early in life. Clostridia are Firmicutes and are resistant to antibiotics which gives them an advantage over other bacteria.
When we take antibiotics, other bacteria disappear while Clostridia proliferate. This is why Clostridium Difficile overgrowth often pops up in people who take antibiotics.
In general, most species in the Clostridia class are harmless, save for a select few. They’re common and are considered a healthy part of the microbiome when controlled. My Clostridia started high at 74.86% pre-antibiotic and rose to 85% 6 weeks post-antibiotic.
This supports the notion that Clostridia are resilient to antibiotics and taking antibiotics can increase them. With Clostridia making up such a large proportion of my microbiome, it seems unlikely that greater diversity was one of my options.
N=1 changes direction
It didn’t take a 5th test for me to realize that my approach wasn’t doing anything. Thus, I didn’t see any point in continuing. But, in June I came upon some research that changed my perspective.
Rather than focus on providing sustenance for my gut bacteria, what if I manipulate other environmental factors in the gut? Things like circadian rhythms, exercise, and sleep. And what happens if I try to leverage other pathways in the gut? I stopped taking the probiotic and fiber blend and went about manipulating these other factors.
One of the keystone principles I identified was that cellular detoxification, inflammation, and tight junction proteins are regulated together. In fact, this phenomenon is present in people with inflammatory bowel disease. These people have impaired cellular detoxification and altered drug metabolism due to the presence of inflammation.
When cellular detoxification pathways are initiated, inflammation gets blocked and tight junction protein expression increased. When inflammation is increased, tight junction protein expression decreases as does cellular detoxification. They work together to regulate the environment of the gut.
I decided to keep my diet the same and just drop the probiotic and fiber supplement. I added in some foods that I’ve always eaten but made sure to eat them on a more regular basis based on my results from 23andme. I also added in a couple of supplemental nutrients that popped up in my research.
These nutrients may not be adequate in the modern human diet as new data indicates. They also could have a dramatic impact on the GI environment and I was going to find out if they did.
If I was right, adding these nutrients will alter the triumvirate of inflammation, detoxification, and tight junction protein expression. This, in combination with maintaining a robust circadian rhythm, should change my microbiome.
After 4 weeks I performed another Ubiome test to see what was doing. Unfortunately, direct comparisons between my previous tests are difficult to make since I was taking supplemental fiber and probiotics. There’s also a 7.5 month gap between the 2 tests. Despite this, there were some pretty interesting results, as seen below.
Above you see a comparison between my Firmicutes:Bacteroidetes ratio. On the top is 11/30/2015 and on bottom 8/12/2016. In early research, a high ratio of Firmicutes:Bacteriodetes(3:1) indicated poor metabolic health, specifically obesity.
But, current research puts this more up in the air. Regardless, the ratio dropped from 4.9:1 to 0.6:1 when compared to baseline. The drop was greater when compared to 6 weeks post-antibiotic, which was 7.9:1.
What happened to all the Clostridia?
The change in focus also tells a completely different story on the Clostridia side of things.
On the left is my Jan. 29 test compared to “All Samples” and on the right is my Aug. 12 compared to “All Samples”. Not only did my Clostridia decrease, but they went from being 52% higher than “All Samples” to 42% less than “All Samples”.
All tolled, they made up just 33% of my new microbiome. That’s more than a 50% drop when compared to my pre-antibiotic test. And then there’s diversity…
Bring on diversity day…
A pleasant surprise is that my diversity actually increased from an inverse Simpson’s diversity score of 5.41 (3rd percentile) to a score of 6.11 (7th percentile). This may seem insignificant, but my score ranged from 5.41-5.62 over the course of the previous 3 tests. It also never cracked the 4th percentile.
Of the many factors related to the microbiome, diversity seems to be the most important and one of the primary outcomes I was shooting for. The science behind the microbiome isn’t in its infancy, it’s still in utero. There’s so much we don’t know, but from basic ecosystem principles we know that a diverse ecosystem is the most stable.
Of course a diverse ecosystem filled with organisms that try to destroy it wouldn’t be good. This is why I modified factors that promote an environment that promotes bacteria that evolved with us.
Drop in fiber and Bifidobacteria massacre aside, other factors are at play in my increased diversity. For one, a new critter popped up that’s inversely correlated with BMI. This new-to-my-gut critter from the genus Christensenella is also a member of the Firmicutes phylum. Although my weight/BMI stayed exactly the same throughout, the belief is that this guy is protective.
Who brought the new guy?
What’s cool about Christensenella is that it appears to be a keystone species and has a tendency to bring friends. This means when they’re around they promote an environment that their friends can hang around in.
In other words, they increase bacterial diversity. If you lose him, he takes his friends with him, decreasing diversity. This may explain the suite of new guys showing up in my data alongside Christensenella. (Wanna read up on the new guy? Check out this Nat Geo article)
These broad changes in gut bacteria show that what I did had a significant impact on my microbiome. But there is that confounder of eliminating probiotic and supplemental fiber intake to deal with. However, this wouldn’t explain the difference between my baseline and most recent test. Neither contained supplemental fiber nor probiotics.
Changing the environment > Taking probiotics
The probiotic part gets interesting as well. Taking antibiotics seemingly destroyed my levels of Bacilli, I mean wiped them out. My Bacilli levels dropped to 32% of baseline 2 weeks post-antibiotic.
At this point the antibiotics were supposed to be completely out of my system. Despite taking the probiotics as directed, this plummeted even further 6 weeks after antibiotic use to 8% of baseline on Jan. 29.
Despite no longer taking Megasporebiotic during my August test, my Bacilli levels rose back to baseline.
When compared to Jan. 29, my Aug. 12 level of Bacilli were 13x greater. This data shows that regulating the GI environment can be a transformative factor in regulating the microbiome. Maybe even more so than taking probiotic supplements.
Unfortunately we can’t tell if the specific strains in Megasporebiotic changed throughout the trial. We also can’t say that it didn’t help, just that transforming the environment allowed a total recovery.
New bacteria, new functions…
Since we’re modifying factors that change your GI environment, different bacterial functions predominate. Functions these new bacteria perform make them more suited to this new environment. Certainly more than the old guys. Much in the same way, changing the Earth to 100% water would completely change the organisms living there, including us.
In my next blog, we’ll take a look at these new functions and what they may be saying about my new GI environment. It seems that manipulating the GI tract caused a large change in the functions performed there. Changes that could have major positive effects on health. This includes lower inflammation, greater polyphenol content, and improved intestinal barrier function. You can find that blog here.
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While bacillus are also part of the firmicutes family, that could in part explain why you had such high firmicute levels, but then that’s odd that your bacillus went DOWN while on Megasporebiotics, since that’s all they contain — five types of bacillus.
Very, very odd.
I agree, very odd. I don’t think it’s an indictment on megaspore, probably moreso Ubiome testing.