A study just began at NYU looking at how porcine whipworms change the microbiota of patients with ulcerative colitis. P’ng Loke is leading it. He conducted an earlier study on a fellow who’d acquired a human whipworm infection, and sent his ulcerative colitis into remission. (I tell this guy’s story in the book. It’s remarkable.)
A major find to come from Loke’s case study was that restoring the mucous barrier could send UC into remission, and that whipworms, which embed head first in the lining of the colon, somehow corrected defects in the mucous layer.
In brief: You get parasites. Your immune system tries to shake them off by increasing mucus secretion. The extra mucus quells the ulcerations. How? The mucus probably pushes back the intestinal microbiota to a comfortable distance. In fact, one theory about UC generally is that commensal microbes have moved too close for comfort, thus the inflammation. Not a question of what’s there, in other words, but how well that teeny barrier is holding.
So now Loke and company are looking at how these worms change not only the mucous barrier, but the microbial ecosystem. Lots of ways to think about this, but here’s one of the most mind-bending.
If you’re inclined to inflammation, your internal microbial communities may shift. Microbes that thrive in an inflamed environment bloom, and others — anti-inflammatory bugs — decline. Like any organism, these microbes actively cultivate the niche that they like, not least because it gives them a competitive advantage over other microbes. So microbes that thrive in inflamed conditions may prompt more inflammation. You see where this goes: a kind of feedback loop. That’s UC. The question is, How to interrupt it?
Back to the mucous barrier. The hypothesis Loke and company are testing is that worms interrupt the unhealthy feedback loop between inflamed host and inflaming microbiota. Your immune system says, Here’s a rather large invader. Get that mucus up and running! And this distraction interrupts the vicious cycle.
Now imagine that, as an organism, you’ve always had parasites present — that, in an attempt to expel them, your mucous secretion system has always been in moderate-to-high gear. Now it starts looking like you depend on parasites for a properly working mucosal layer. Also consider the particular lifecycle of the human whipworm: although it embeds itself into the intestine, it doesn’t suck blood. Rather, it seems to live off intestinal secretions — mucus included.
So now you begin to wonder: Are you really secreting mucus to flush out the parasite, or is the parasite prompting mucus production because that’s what it eats?
The field is rife with these sorts of about-faces—flipping phenomena over and examining them from the backside. And in many cases, the answer is probably that they’re both true. They’re not mutually exclusive, at any rate.
I was talking with William Parker at Duke the other day. I mentioned this work — whipworms, the mucosal barrier and such — and he corrected me. It’s not a barrier, he said. It’s an ecosystem. The mucosal ecosystem.
