Monday, May 6, 2013

The Microbiome and T1D

I have one word for you: microbiome.

There has been a lot written about it lately, including a good article in the October 22, 2012, New Yorker by Michael Specter in which he lays it out better than I could:

"As we pass through our mother’s birth canal, we begin to attract entire colonies of bacteria. By the time a child can crawl, he has been blanketed by an enormous, unseen cloud of microorganisms—a hundred trillion or more. They are bacteria, mostly, but also viruses and fungi (including a variety of yeasts), and they come at us from all directions: other people, food, furniture, clothing, cars, buildings, trees, pets, even the air we breathe. They congregate in our digestive systems and our mouths, fill the space between our teeth, cover our skin, and line our throats. We are inhabited by as many as ten thousand bacterial species; these cells outnumber those which we consider our own by ten to one, and weigh, all told, about three pounds—the same as our brain. Together, they are referred to as our microbiome—and they play such a crucial role in our lives that scientists ... have begun to reconsider what it means to be human."

These colonies of bacteria have been under attack--each time one of us takes broad-spectrum antibiotics our microbiome takes a hit--and, in modern times, each successive generation is born with fewer of them. Some scientists think that destruction of the microbiome is responsible for increasing rates of asthma, Crohn's disease, severe allergies, and other conditions--including Type 1 diabetes.

This was the gist of a talk Mark and I went to a couple weeks ago, organized by the JDRF, which sponsors research into the prevention, treatment, and cure of T1D. The talk was part of their spring research briefing, where they give donors a sense of the lines of inquiry that their money is funding.

During the cocktail hour beforehand, Mark and I talked about what an unexpected turn our lives have taken. Who could have believed a year ago that we'd be spending an evening at a Sheraton in the suburbs, eating fruit or "mashed potato martinis" (actually, they were pretty good), and needing to know about the latest thinking on type 1 diabetes?

All of the talks were good; I'll summarize the most salient parts of them here, though frankly, they were not easy for someone like me, with no medical or scientific background, to understand. But the one that really grabbed our attention was by Ramnik Xavier, an MD, Ph.D. at Harvard who runs a lab at MGH studying the microbiome.

Here are some of the things we learned; I have done my best to rephrase them for the lay person.

From Dr Julia Greenstein, vice president of cure therapies at JDRF:
Since 2001, scientists have been able to replenish peoples' beta cells (the cells that produce insulin) through islet transplantation from cadavers. The catch is that, without heavy doses of immuno-suppressive drugs, the body will attack these foreign cells. So right now, for most people, the cure is worse than the condition. So far, this technique has mainly been used on people with severe hypoglycemic unawareness--meaning they cannot feel dangerous lows of their blood sugar. A potential cure for T1D would be to figure out a way to keep the body from attacking the healthy new beta cells: "We have to take those cells and figure out a way to put them in a bubble."

(Hypoglycemic unawareness is something we have to watch for with Bisi. Right now, if she's low, meaning a blood sugar below, say, 70, she tends to be cranky, hungry, and a bit out of sorts. The worry is, if you experience too many lows, your body may start to think this is "normal" and you will no longer feel the warning signs. Of course, Bisi's condition has made all of us more attuned to how we feel before and after meals. Recently, after exercising and on a day when I hadn't had a big lunch, I felt very shaky and hungry. I told Bisi, and we decided that I'd test myself with her meter. It turned out I was at 62--right at the borderline of what's too low for someone without diabetes. Bisi's target range is higher--from 80-180--so she has more of a protective cushion for the lows. But I think this shaky-hungry feeling is similar to what Bisi feels.)

Greenstein also talked about how scientists' understanding of beta cells and diabetes is evolving. People used to be taught that someone with T1D had zero beta cells left. But in some cases--maybe in all cases--that turns out not to be true. She pointed to the example of a man who had had T1D for 50 years and upon his death gave his pancreas to the Joslin Diabetes Center for research. It turned out that his pancreas still had some beta cells. If researchers could figure out how to proliferate and protect these remaining cells, that might help give diabetics better control of their blood sugar.

Greenstein moved on to talk about preventing T1D in those who are prone to it. The incidence of T1D is doubling every 20 years--a startling increase. And more people are being diagnosed at a younger age. While Mark and I were told in the hospital that T1D comes on very suddenly, when the immune system starts attacking the pancreas, Dr. Greenstein had a slightly different take. She explained that when the immune system starts attacking the pancreas, you start losing beta cells. But people usually aren't diagnosed until they've lost 80 percent of those cells. The goal is to diagnose people earlier, when fewer of their beta cells have been destroyed, and to figure out a way to stop the autoantibody response. Her interpretation fits Mark's and my view of Bisi's disease--as I've mentioned before, we feel like she was experiencing fluctuations in her blood sugar long before she was diagnosed.

Even better than diagnosing people earlier would be to keep the T1D process from starting in the first place. To this end, another line of research is "primary prevention"—universal childhood vaccination, which would in theory protect children from developing the disease.

Dr. Michael Brehm, an assistant professor in the Program in Molecular Medicine at UMass Medical School, talked about his efforts to study the T1D process from A to Z through "humanized" mice. "These mice are like test tubes, they have no immune system, so you can implant various disease into them." Once his lab understands how T1D works in these mice--from the initiation of the auto-immune process to progression of the disease--they can test both what triggers the disease and how to cure it.

Dr. Jeffrey Karp, an associate professor at Harvard Medical School, Brigham and Women's Hospital, talked about the use of "biomaterials" to encapsulate or protect beta cells from being destroyed by the immune system of someone with T1D. Much of his talk and research work does not really have to do with T1D (in fact, someone in the audience yelled, "We're here to learn about type 1 diabetes!!"). But part of JDRF's goal, as Dr. Greenstein pointed out, is to be multi-disciplinary--to see how existing or developing medical technologies and thinking can be applied to T1D.

Okay, now back to where I started, with the microbiome and how it could potentially tie into T1D.

JDRF has been funding the work of Dr. Xavier, who is looking into the potential ties between T1D and the gut bacteria in our microbiome. The microbiomes of people with T1D are different from those without, and scientists speculate that decoding these differences could help us understand why some people get T1D and others don't. As Xavier explained, his introduction to T1D "stemmed from an observation that in certain parts of the world there has been an explosion of T1D incidence: I think it could be because of the bugs in the gut." Xavier pointed to a study of two genetically similar populations--one in Finland, the other in Karelia, part of Russia. The population base is the same, but in the last several decades, the standard of living has risen much faster in Finland than in Karelia--and so has the rate of T1D. Finnish children now get T1D at six times the rate of their Karelian counterparts. "The genetics are almost totally similar—something is different. What is it?" (Last month's Smithsonian magazine has a good explanation of this research.)

Could it be higher use of antibiotics, which can damage the microbiome (Xavier cited the work of David Relman at Stanford). Could it be, because of fewer vaccinations or poorer health care, that the immune systems of Karelian children face more bacterial challenges than those of Finnish children, and that their gut bacteria is therefore different? Could it be differences in the types of food the two populations eat? (Consuming probiotics is another way to alter our gut bacteria, though Dr. Xavier, among others, says that none of the over the counter probiotics that have grown so popular in the U.S. has been shown to be of any use.)

Xavier is trying to understand the precise "bacterial signature" of the microbiome of children with T1D. How exactly is it different from those of healthy children? Could material from someone's "healthy" gut be injected into the gut of someone with T1D? Would it help? Are the gut bacteria different in diabetic children with "tight" glucose control versus poor glucose control? Xavier has "roomfuls of data we need to analyze" on the microbiomes of Finnish children with and without T1D. He sees understanding differences in the microbiome as a potential way to prevent, treat, or even cure T1D. In the meantime, he told me via email, there's not much we can do to support Bisi's gut bacteria other than have her eat yogurt and avoid antibiotics unless she really needs them. This line of research makes sense to us and feels like it has some promise. Until then, it's a good thing that Bisi likes yogurt.


  1. I love the part about how you tested yourself on a day when you were feeling hungry and shaky - I'm sure that made Bisi feel good!

  2. My daughter is 6, she's taken antibiotics perhaps once in her life. My husband and I are sitting here trying to remember. Anyway, we're not even sure she ever had before she was diagnosed with type 1 march 10, 2013. He himself was diagnosed 14 years ago, initially with type 2, now he's labeled LADA. Thanks for summarizing all the research. It is fascinating. We heard a bit of these summaries at a parents seminar at a diabetes camp family weekend. It's hopeful, but it's been hopeful for such a long long time.