Can parasites prevent autoimmune diabetes?
A guest post by Moises Velasquez-Manoff.
Coronado Biosciences, a company seeking FDA approval for a type of medicalized parasite, recently announced the beginning of a very interesting trial on Type 1 diabetes.
Coronado is running a number of studies with a whipworm called Trichuris suis, which is native to pigs. It’s testing the parasite on several immune-mediated disorders, including Crohn’s and psoriasis. Early studies on inflammatory bowel disease showed tremendous promise.
The study on type 1 diabetes is particularly interesting, however, because rather than treat an existing disease, the trial will attempt to PREVENT its emergence. Prevention, obviously, is the best medicine. And one of the tantalizing but-not-yet-fully-realized promises of Darwinian medicine — of bearing in mind the ancestral environment that shaped the human organism — is that it allows for novel hypotheses as to how diseases emerge, and how to head them off entirely.
In this case, the idea is that a timely introduction of parasites could squelch an incipient autoimmune storm.
Type 1 diabetes is much more common among carriers of certain variants of the human leukocyte antigen HLA-DQ, an immune-system gene. Disease onset is predicted by the appearance of two types of self-directed antibody. But you can display one of these antibodies without yet having the disease. So the scientists running the study will know who’s on the path to developing autoimmune diabetes before it becomes overt.
And they’ll intervene with worms.
How might parasites help? Type 1 diabetes results from a breakdown of tolerance toward one’s own tissues—in this case, the insulin-producing islet cells of the pancreas—and their subsequent destruction. As part of their survival mechanisms, parasites suppress the host immune system. At the cellular level, they induce a range of anti-inflammatory cells and proteins in your body. This strong anti-inflammatory signal may nudge the immune milieu toward tolerance, preventing the cascade of events that leads to autoimmune diabetes. The hope is that the attack on islet cells will never materialize.
That’s one way whipworms may help. But there’s another slightly more complex and intriguing possibility: parasites may stabilize the microbiome.
Work by P’ng Loke at NYU suggests that whipworms, which partly embed themselves in the lining of the colon, spur mucus production. No one really knows why. Perhaps it’s your body’s attempt to expel the parasites; perhaps the worms, which are thought to feed off intestinal secretions, prompt you to secrete more mucus because they’re farming you.
Whatever the case, the rebooted mucus production, Loke has found, has the bystander effect of healing lesions in ulcerative colitis, a painful inflammatory disease of the large intestine. He’s observed this phenomenon in one human, and several monkeys. Captive macaques develop spontaneous colitis much like modern humans. In both primates, the parasites sent the disease into remission.
When he monitored the microbiome of parasite-treated macaques, he noted that the intensified mucus production seemed to shift the microbiome from a diseased state back to a healthy one. Therein lies an important lesson. It’s turning out that mucus is much more than just unsightly goo; it’s a growth medium for our indigenous bacteria. When we stop producing it, we not only lose a very necessary barrier between ourselves and our microbes, we select for a different microbial community entirely, one that’s less friendly.
What does this have to do with type 1 diabetes?
In 2011, a team of Finnish and American scientists published a small but very interesting study on the “autoimmune microbiome” in type 1 diabetes.
They followed at-risk newborns for several years—kids with the diabetes-associated genotype—periodically analyzing the infants’ poo. The scientists noted that certain telltale signs PRECEDED the development of diabetes. First, autoimmune microbiomes were impoverished compared to those from children who didn’t develop the disease, suggesting that a loss of microbial diversity was pathogenic; their microbial communities were also prone to wild swings—blooms of some bacteria and declines of others—indicative of ecosystem instability. And whereas healthy children presented a microbiome that stabilized in a predictable fashion, converging over time on a seemingly preordained makeup, the autoimmune microbiome never stabilized. In ecological parlance, you might say that it never reached an apex community. It remained an impoverished ecosystem dominated by virulent, weedy species.
Why suspect this is cause not consequence? That’s always a tough question. But in rats, certain lactobacilli strains—keystone species—have been found to prevent diabetes onset in animals otherwise prone to the disease. More importantly perhaps, the scientists conducted a “metagenomic analysis” of this autoimmune microbiome. They looked at the genes present in the community, and what they did.
Compared to controls, children who developed diabetes lacked bacteria that degraded mucin, a glycoprotein abundant in mucus. They also had fewer bacteria that produced lactate and butyrate, two microbial by-products thought to be essential to gut health. These acids also prompt mucus production. (In fact, certain cells lining the colon derive their energy supply directly from resident microbes in the form of butyric acid.)
The takeaway was this: these children lacked bacteria that, through the production of lactic and butyric acid, spurred mucus production; and they didn’t have the friendly bacteria that would have been selected by a healthy mucus substrate. As a result, their gut barrier was defective. They suffered from what’s sometimes called “leaky gut.” And an overly porous intestinal barrier has been implicated in a number of autoimmune and inflammatory disorders.
The question is, can parasites stabilize this aberrant microbiome and heal the mucus barrier? And in doing so, will they prevent this autoimmune disease?
If so, I predict fireworks. Too bad we have to wait years to see.
Moises Velasquez-Manoff is author of An Epidemic of Absence: A New Way of Understanding Allergies and Autoimmune Diseases, published by Scribner.