Bacteria in the Gut Offer Clues to Diabetes
Scientists find different microbes in lean and obese people
You're not alone. Literally. The human body teems with trillions of bacteria. Terrified? Don't be. These mostly friendly inhabitants are not only microscopic, but they are usually confined to a few well-guarded domains and provide a variety of important services to their human hosts. Even so, experts think that sometimes these bacterial communities can get out of balance, triggering diseases.
The bacteria that live in the stomach and intestines, also known as "gut microbes," have been linked to both type 1 and type 2 diabetes. Not much is known for certain about the connection, but the rapidly growing field of research into gut microbes may someday yield a new biological arsenal in the fight against diabetes.
Meet Your Guests
The bacterial world contains incredible diversity, with millions to billions of species that can do anything from breathe sulfur to swim in acid. Of the thousands of species that have been discovered in and on the human body, most have never been seen anywhere else. An ongoing endeavor by the National Institutes of Health called the Human Microbiome Project is attempting to classify and characterize this vast array of tiny inhabitants.
The womb is a sterile, bug-free environment, so at birth, humans are mostly, well, human. The first bacteria a newborn encounters are typically in Mom's birth canal. Within the first few years of life, though, bacteria from a variety of sources colonize certain hospitable realms of the body, including the gastrointestinal tract, skin, mouth, and vagina. By the time one is an adult, bacterial cells in the body outnumber human cells by an estimated 10 to 1.
While gut microbes get to enjoy a warm dwelling and ample food, they supply their host with a number of perks, making for a generally happy cohabitation. "At first we thought bacteria just produced vitamins, but bacteria do other things," says Matam Vijay-Kumar, PhD, an assistant professor of pathology and laboratory medicine at Emory University. Bacteria in the gut can break down foods that humans alone can't, like some types of fiber, giving their host an additional source of nutrition that may account for up to 10 percent of daily calories. Another bonus is that bacteria protect their turf from nefarious invaders, such as a troop of salmonella on the attack.
Most of the bacteria that inhabit humans appear to fall into some basic broad categories. Yet, upon closer inspection, researchers have found that the communities that reside in one person can look remarkably different from those that live in someone else. These differences could be important: They may be a reason why some people are healthier than others.
The factors that shape and cultivate each person's interior microbial world are both genetic and environmental. Scientists know, for example, that members of human families tend to house similar strains of bacteria. The body's immune system, which is also a product of genetics and environment, is of particular importance to bacterial communities. One of its jobs is to keep the bacteria in the gut where they belong, even while the bacteria test boundaries. Some bacterial species may get along better with the immune system than others. Emerging evidence suggests that the relationship between certain gut microbes and the immune system may be a critical factor in the development of type 1 and type 2 diabetes.
Bacteria and Weight
For starters, researchers suspect that gut microbes can affect weight, which has known associations with type 2 diabetes. Different bacterial species are dominant in the guts of lean and obese people, even in identical twins of different weights, according to a 2008 study published in Nature. These differences boil down to the relative abundance of two types of bacteria: firmicutes and bacteroidetes. Obese people tend to have more firmicutes, which are very good at squeezing energy out of food. Lean people generally host more bacteroidetes, which are less efficient calorie extractors. This suggests that people may become overweight at least in part because their gut microbes provide them extra calories.
An earlier study by the same group found that populations of these two types of bacteria actually shift as people lose weight, from more to less efficient bacteria. Another difference they discovered is that lean people have more bacterial diversity than obese people in their gut microbes. "Any environmentalist will tell you a more diverse population is better than a less diverse population," says Eric Triplett, PhD, a professor of microbiology and cell science at the University of Florida.
If the link between obesity and gut microbes holds up, losing weight may someday simply be a matter of changing the populations of bacteria in obese people to be more like those in lean people. Some research suggests that a person could shift bacteria populations by eating the foods that slimming bacteria prefer. A 2010 study in Cell found that populations of bacteroidetes in mice get a boost if they are fed a diet rich in a particular carbohydrate. Another possibility would be using antibiotics to tweak bacteria populations to help their human host lose weight.
Microbes and Type 2
While the evidence is mounting that gut microbes affect weight, some research suggests that their influence on type 2 diabetes is independent of weight and is instead related to the immune system. "The gut immune system is very specialized. It has so many ways to make the bacteria calm down. It's an enormous task for humans," says Vijay-Kumar, the lead author of a provocative 2010 study published in Science. The research involved mice with a specific genetic mutation that compromised the part of their immune systems that keeps gut microbes in check. These mice fattened up and developed insulin resistance, a hallmark of type 2 diabetes, as well as unbalanced blood fats and high blood pressure. The altered immune system also affected the diversity of their gut microbes.
The immune-compromised mice had increased inflammation, too. "The current hypothesis is that low-grade chronic inflammation drives insulin resistance," says Vijay-Kumar. While excess weight is often pointed to as an inflammation trigger, Vijay-Kumar and his colleagues showed that insulin resistance in their mice wasn't related to weight gain. Plus, normal mice became insulin resistant when given gut microbes from the immune-deficient mice.
While any treatment for obesity or type 2 diabetes that would come from research in gut microbes is years away, a couple of studies show how such therapies might work. And it's possible that many obese people with type 2 diabetes have already experienced the benefits of altered gut microbe populations after undergoing bariatric (weight-loss) surgery. It's well known that in most people with type 2 diabetes who have bariatric surgery, diabetes quickly and mysteriously goes into remission. A 2009 study published in Proceedings of the National Academy of Sciences found that gut microbe populations became radically different after bariatric surgery and perhaps facilitated weight loss and blood glucose control.
At the 2010 meeting of the European Association for the Study of Diabetes, a Swedish team presented intriguing research. (It's not for the fainthearted, though.) First, obese men with prediabetes had their bowels cleaned of bacteria. Then the gross part: To repopulate their guts with microbes, half of the men were given bacteria from their own feces while the others were given those from the feces of lean donors. Six weeks later, compared with those who got their own microbes back, the men who got microbes from lean people became more sensitive to insulin and had better blood fat levels.
Type 1 and the (Inside) Environment
As type 1 diabetes has become more common in recent decades, scientists have sought an environmental explanation of why. But the environment isn't limited to what is outside the body; there's also the bacterial environment within. Indeed, evidence is growing that gut microbes may play a role in the development of type 1 diabetes.
A 2008 study published in Nature found that mice prone to developing type 1 diabetes were protected from the disease by having their immune systems altered. However, if the mice were stripped of their gut microbes, the immune protection no longer worked. It's not entirely clear how gut microbes could protect mice from type 1, but the results square well with the "hygiene hypothesis." This is the theory that if people don't come into contact with enough germs during their formative years, their immune systems won't develop properly, raising the risk of autoimmune diseases like type 1 diabetes. Another possibility is that having the wrong gut microbes could lead to the problems in the immune system that precipitate type 1. An abnormal microbial community could cause the gut to "leak" bits of bacteria into the body, says Triplett. "That causes chaos in the immune system. We want to find out what triggers this."
Gut microbe research in humans with type 1 is still scarce, but a small 2010 study published in the ISME Journal provides preliminary evidence supporting the link. Triplett and his colleagues analyzed gut microbes from children at high genetic risk for type 1 diabetes, starting when they were young. Over time, the gut microbe populations of those who would go on to develop type 1 began to change markedly from those of the children who remained free of diabetes. These differences were apparent "even at 4 months of age," says Triplett. Their results may also support the hygiene hypothesis. "Over time, the healthier kids developed more [microbial diversity], which could mean they are exposed to more things." The researchers are working on verifying their results in a much larger population. Triplett hopes that will help them detect kids at high risk for developing type 1 and identify environmental factors that affect the diversity of gut microbes.
It's possible to envision a day when preventing type 1 and type 2 diabetes would just mean, say, eating a special yogurt filled with antidiabetes bacteria. Until such a day, scientists will continue to learn about the ecosystem within the body and what it means for human health. In the meantime, you can take comfort in the knowledge that wherever you go, you're never on your own.