I work at a microbiome science startup. This might sound glamorous or high-tech, but we are—in effect—turd wranglers.
See, in the few studies that have been done, a fecal transplant from a healthy person is a surprisingly good treatment for autism, Parkinson’s, and a host of other diseases that you’d never expect. We’re trying to figure out which bacteria in poop are the important ones, and turn them into probiotics so that we can treat these diseases without putting someone else’s shit up your ass.1
To that end, we’ve recently gotten some promising data back from an animal experiment, where we fed rats a species of Bacteroides that converts glutamate to GABA in the GI tract.
Glutamate, in addition to being the most abundant amino acid in the diet, is also the main excitatory neurotransmitter in your body. GABA, on the other hand, is the main inhibitory neurotransmitter, and Bacteroides is the most abundant genus in most people’s microbiomes. All this makes a GABA-producing Bacteroides seem like a good place to start, in the search for probiotics that can improve mental health…and hey, it turned out that the strain we tested could reverse some of the behavioral and molecular effects of chronic stress in rats.
So last week, I got to go to a neuroscience conference and present a poster reporting our results. In chatting with some scientists who stopped by the poster, someone asked a question that we get fairly often: why not just engineer a Lactobacillus or something to do it instead?
It’s a natural question, especially because neuroscientists are an ingenious bunch that use some absolutely insane tools in their day-to-day work. (Want to see which parts of the brain are wired into the fear response in your animal? Just inject its amygdala with some RabV CVS-N2c(deltaG)-tdTomato, a heavily nerfed version of the rabies virus that expresses a fluorescent protein, which will conveniently travel backwards across the synapses and infect all the brain circuits that have input onto the fear-processing center, making them light up bright red.)
There ARE people taking the approach of engineering probiotics, and I wish them all the best. But we are humble poop ranchers, and we’re not trying to reinvent the wheel.
I always compare Lactobacillus and Bifidobacterium to cats and dogs, in that they were the first two animals humanity domesticated. They’re mostly harmless, and certain breeds are great for things like keeping the house clear of mice. But they’re inherently limited in what they can do: there’s no breed of dog that’s big enough to ride around on, or pull a plow.
With a lot of time and effort, you might be able to create one, through careful breeding or genetic engineering…but even if you succeeded, you’d probably end up with a breed that gets horrible back problems and dies at three years old because its cardiovascular system just wasn’t cut out for that much muscle.
It sounds like an awful lot of work, is what I’m saying…especially when horses already exist.
We’re not engineering probiotics because, if there’s a function that the human body needs, and a microbe is capable of fulfilling it, that microbe is probably already out there somewhere. Not only that, it’s probably better at its job than whatever we’d be able to whip up in the lab, because it’s had millions of years to adapt to its niche in the ecosystem in complex ways we don’t understand yet. Bacteroides don’t just produce GABA, they makes short-chain fatty acids, vitamins, exotic compounds like commendamide. They fight off pathogens, starve them out, eat them. They’re a part of the natural world, red in tooth and pseudopod, reflecting all her elegance and wildness.
There is, of course, some danger inherent to working with a wild thing. That’s the main draw of trying to engineer a gene into an existing probiotic like a Lactobacillus—you’re starting from something presumably safe, and adding one or two features you’re sure you’d like. The only danger there is the danger of failure.
But a coward dies a thousand times.
We’re not engineering probiotics because…well, why stop at cats and dogs, when there’s a whole kingdom of life out there waiting to be brought to heel? As a species, we’ve declared dominion over the creatures of the macroscopic world. The microscopic one is harder to see, but it’s no less exciting of a frontier—because when you start to get to know these little beasts, you realize that the domestication of bacteria is going to have just as big an impact on humanity’s future as the domestication of animals had on the past.
Imagine being woken in the predawn light, at the break of some prehistoric day, by the sound of a friend saying your name. You open your eyes, and he’s standing there, staring across the plains into the distance.
“Get up,” he says, not turning his head.
You follow his gaze. After a moment, the dim shapes in the distance resolve into a herd of wild horses.
As you rise to your feet, he turns to you, and now you can see there’s a dangerous glint in his eye. A wild, insane look, with a vision behind it. One of glory, of riding on thundering hooves. In his hands, he’s clutching a woven rope.
“Come on,” he says. “I’ve got an idea.”
That’s where we are right now. It’s gonna be a big day.
—🖖🏼💩
Oral capsules are also an option. I feel like which ROA you’d prefer, given the choice, says something about you—though I’m not sure what.
>(Want to see which parts of the brain are wired into the fear response in your animal? Just inject its amygdala with some RabV CVS-N2c(deltaG)-tdTomato, a heavily nerfed version of the rabies virus that expresses a fluorescent protein, which will conveniently travel backwards across the synapses and infect all the brain circuits that have input onto the fear-processing center, making them light up bright red.)
holy shit, that is truly a wild idea.