Tuesday, July 13, 2010

Our parasites, our selves

There’s a pretty good article in the NY Times this morning illustrating how having the right bacteria in your gut is essential to good health, the subject of a journal article that I wrote about earlier. We have co-evolved with the microbes in our environment, and they have ways of recognizing when they’ve reached a good home.

In addition to the trillions of bacteria in our gut, there are other residents of our intestines that we have evolved with—the myriad types of worms that parasitize us. Given the deservedly bad reputation of whipworm, ringworm, tapeworm, schistosomes, and their helminthic ilk, it comes as a surprise that the last ten years of research indicate that these worms can actually do us some good.

Our immune systems evolved in a world of worms; the worms evolved in the world of our immune system. For a worm to survive in our gut it has to somehow survive the assault of our immune system, and so evolution has favored those worms that have figured out how to tame an immune response. For us to have survived with such parasites, our immune system evolved with the assumption that it’s being restrained. If, with modern hygiene, the reins are off the immune system, it can run wild. So, we in the modern western world are far more likely to have allergic reactions and autoimmune disorders. If you can stomach it, you can now effectively treat your allergies not with antihistamines, but with intestinal worms purified from other peoples’ poop.

So far, most of the research on the interaction between human and worm has focused on the human half of the equation—exactly what immune cells are being stimulated and suppressed by the worms. People are now trying to understand the worms’ point of view.

Worms infect our guts, and use the nutrients that they steal from us to produce millions of eggs, which we spread by defecating. These eggs can infect another human when the eggs are eaten; it's polite to say that it’s oral-fecal contamination, but really it’s just getting stuff in your mouth that has some s#!t on it. The eggs don’t want to hatch until they are in the human gut, but what I find surprising is that the eggs do not recognize the human gut. The way they know that they’re in a human is by recognizing the bacteria that live in our gut. It's only when they see the right bacteria that they hatch (here's the movie):

A group of researchers at the University of Manchester studies whipworm, and tried hatching whipworm eggs in vitro. Initially, they found that the eggs hatched only if there was some material from the host animal’s gut present. Using a microscope, they found that the ends of the eggs that were ready to hatch were covered in bacteria (here treated so that they glow green).

Some further experimentation showed that most of the inhabitants of the animal gut worked to trigger egg hatching, and that direct contact between the egg and the bacteria was absolutely necessary for hatching. But what is the nature of the interaction between bacteria and egg? Intestinal Bacteria produce a variety of protein structures that allow them to stick to their hosts’ cells. The “fimbriae,” or fringes, are little filaments of protein with extra-sticky proteins at their ends:

Bacterial cells that couldn’t make fimbriae, or those that had their fimbriae covered up, were both incapable of triggering egg hatching. So, that’s the bacterial side of the interaction; the worm’s egg side remains a little hazy, but the researchers guess that there is a receptor on the egg that is triggered by the fimbrial protein.

One cool aspect of this study is that they were able to show that this relationship has real-world significance. The researchers used mice, and treated them with strong antibiotics to remove most of the bacteria from their guts. After two days of this treatment, the mice were infected with whipworm eggs. After 18 days, they had about a third as many intestinal parasites as their siblings who had not been given antibiotics. That’s the good news; the bad news is that they have a rather extreme immune response to the worms, probably on account of not having enough bacteria in their guts. And of course, if worms do become established, they further regulate the immune system.

Hygiene is good—nobody argues for a return to the bad old days, in which pretty much everybody had multiple infections and suffered the harm they caused. But allergies and autoimmune diseases are bad. Hopefully, we will eventually understand the complicated evolutionary ménage a trois of ourselves, our bacteria, and our worms, and we can reach an equilibrium without worms or dust allergies.

K. S. Hayes, A. J. Bancroft, M. Goldrick, C. Portsmouth, I. S. Roberts, and R. K. Grencis (2010). Exploitation of the Intestinal Microflora by the Parasitic Nematode Trichuris muris. Science 328:1391-1394.

Picture of Fimbriae from Brock Biology of Microorganisms

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