For those of you who are vigilant microbiome news junkies, you may have already come across this one last week: researchers found that inserting a major class of human gut bacteria — Clostridia — into mice with peanut allergies eliminated the allergy. And they found that inserting the other major class of human gut bacteria — Bacteroides — did nothing to alleviate the allergy.
If you’ve been following this blog for a while, you know that this is the class of bacteria, more than any other, that we like to obsess over around here.
Clostridia are the bacteria that make up the majority of people’s “Firmicutes” in gut reports. That’s why I’ve tended to use them a bit interchangeably in the past (though I should probably stop that). They are usually broken into two clusters: Ruminococcaceae and Lachnospiraceae (also often called Cluster XIVa and IV). And those are the exact clusters that were found to ameliorate the allergies. And Bacteroides are the other side of the coin — they tend to make up majority of the other major gut phylum, Bacteroidetes.
The most important, and longest running argument on this blog, has been about Clostridia/Firmicutes: they grow on fermentable fiber from plants and are the main beneficiaries of resistant starch intake, they are the ones that produce the majority of short-chain fatty acids like butyrate, and they seem to be universally correlated with health promotion. Lower Clostridia? Almost never good. And the other dominant, and related argument on this blog has been this: that these effects are due to their interaction with the immune system. Remember, it is said that 70% of our immune system is in our gastrointestinal system. All these people experiencing sleeping/dreaming effects with resistant starch? Probably the Clostridia, and their SCFAs, modulating the immune system.
And the general theory I put forward in this post, about what exactly makes Clostridia so special, was this: that from the little research I could dig up, Clostridia seem to be the adherent bacteria in the human gut. That they are the ones residing in the mucosal layer, acting as a defensive barrier, providing SCFAs to the epithelium, and thus directly communicating with our immune system. The other bacteria, like Bacteroides, seem to inhabit the luminal space — the hollow cavity of the intestine.
So…was that right? The researchers who conducted this recent peanut allergy study sure seem to be saying exactly that:
“These bacteria are very abundant and they reside very close to the epithelial lining, so they’re in intimate contact with the immune system,” Nagler says.
In one quote, we get significant support for two major lines of argument from this blog: that Clostridia are a special and important class of gut bacteria in the human gut because they are the mucosal-adherent bacteria, and because they modulate the immune system.
In case you were interested in the nitty gritty of this particular study, it looks like the Clostridia eliminated the allergies through regulation of an immune modulating cytokine, just like we talked about in the sleeping & dreaming post:
To identify this protective mechanism, the researchers studied immune responses to bacteria in the gut. Genetic analysis revealed that Clostridia caused innate immune cells to produce high levels of interleukin-22 (IL-22), a signaling molecule known to decrease the permeability of the intestinal lining. Children with food allergies are know to have greater permeability in their guts when they eat problem foods.
In a second part of the experiment, the antibiotic-treated mice were either given IL-22 or were colonized with Clostridia. When exposed to peanut allergens, mice in both groups showed reduced allergen levels in their blood compared to controls. Allergen levels significantly increased, however, after the mice were given antibodies that neutralized IL-22, indicating that Clostridia-induced IL-22 prevents food allergens from entering the bloodstream.
As for how, exactly, Clostridia modulates this immune signal, the researchers stayed pretty general. As you know, we’ve focused on short chain fatty acids as the likely mechanism (but have certainly kept the door open to other possibilities):
“They are always signaling to our bodies, but we’re not usually making a response to them. We found they generate particular signals that promote the production of mucous and natural antibiotics the body makes to reinforce the barrier [of the intestinal lining] and prevent those food allergens from getting past the epithelial barrier and into our blood,” said Nagler.
Alright, enough of this victory lap stuff. Time to vent some frustration.
While this study is a really great one to see, the ultimate conclusions drawn by the researchers, both in the study and the media reports, is disappointing, to say the least. Why? Because both in the study itself and in the many news reports about it, what the researchers say essentially amounts to this: “We need to put Clostridia in a pill.”
Nagler and her university have filed for a patent application on the new findings. The ultimate goal is to “interrupt [the allergy] process by manipulating the microbiota,” she says—a probiotic consisting of Clostridia could be a new allergy therapy, for example. Nagler knows of none on the market yet, and they would need testing in people before becoming a treatment of choice.
“The exciting implication for consumers is this gives us a way to intervene and see if we can now use modulation of the bacteria in our gut as a way to prevent or treat food allergies,” Nagler said. “We could use the Clostridia to develop a novel, new treatment we can give to people with food allergies, or to protect people before they get food allergies, to elicit this barrier protective response. This is a totally new probiotic.”
Nagler said that several companies are already working to develop this new probiotic. “In fact,” she added, “we are working with one company. Clostridia are very difficult to work with because they can’t be exposed to oxygen. The good thing about them is they form very stable spores that can live under very extreme conditions. We can potentially collect spores of Clostridia and create them as a pill.”
Clostridia bacteria are common in humans and represent a clear target for potential therapeutics that prevent or treat food allergies. Nagler and her team are working to develop and test compositions that could be used for probiotic therapy and have filed a provisional patent.
Sigh. Big, big sigh.
First things first: I find it pretty disturbing that the first thing health research labs do, once they make an important discovery about human health, is to immediately file a patent. Furthermore, it’s one thing to patent some kind of novel, synthetic, chemical drug, and another to patent something that’s essentially a part of and produced by the human body. These are native human gut bacteria. You’re patenting the idea of putting them in a pill? What’s next, a patent on Vitamin C chewables?
Which brings us to the real reason I find this so frustrating: everything about this study, and everything we know about Clostridia in the human gut, points to the fact that probiotics are not the answer.
As I just said, these are native human gut bacteria. They live and grow inside of you. They can’t survive outside of a human. They exist because you exist. They need you, you need them. Heck, the researchers said it themselves!
“Then we tried to find out which bacterial population it was, and in a whole series of experiments, we settled on Clostridia, which are oxygen-sensitive bacteria,” Nagler said. “They can’t live outside of an environment that is oxygen free. Deep inside your body, deep inside your intestines, there’s no oxygen, and that’s where this kind of bacteria live.
In other words: you don’t need to “seed” or “infect” yourself with these bacteria, as if they are some exotic, hard to acquire bug. Don’t believe me? Here’s the proof: EVERY SINGLE INDIVIDUAL GUT REPORT I HAVE EVER SEEN CONTAINS THESE BACTERIA. I have never seen a report showing no Clostridia. Not one. If you are a human, then you almost assuredly have Clostridia in you.
What DOES differ, from person to person, is the amount. In some, they are the predominant bacteria. In others, a tiny fraction. And what do you think accounts for that? Do some people have access to a magical Clostridia tree? Is there a secret, members-only Clostridia CSA you need to join?
From everything we’ve gathered here on this blog, it’s quite clear that the quantity of these bacteria aren’t related to some type of external exposure. Rather, they respond to the intestinal environment and the inputs into that environment. Clostridia grow when you feed them plant fibers, and they thrive in an acidic intestinal environment — one where a lot of fiber fermentation is taking place, which itself drives down the intestinal pH. Which means that not only a lot of fermentable plant fiber, but also a diversity of fermentable plant fiber, is a pretty good bet.
In other words: if a rainforest is dying because it isn’t raining enough, you don’t plant more trees. You make it rain more. Get it?
As for the question of why this fact isn’t abundantly clear to, or promoted by, the researchers who conducted this study, I think that’s patently obvious. Don’t you?