bugs001It doesn’t sound very enjoyable, but 18,000 of your fellow citizens have signed up to participate in the American Gut Project  ̶̶  before it has even started.

Researchers at universities around country will be recruiting large numbers of people to contribute samples of the microbes that live in their intestines. The goal of the project is to collect a large database of information about these bugs, and they will use genome sequencing to differentiate and identify hundreds of different species.

With the advent of microprocessors in the 1990’s, computers were able to handle massive amounts of information. This allowed scientists to take a small peice of DNA and map the entire genetic code of an organism in a process called genome sequencing. In the last decade, improvements in the technology behind this process have made it more accessible and less expensive, and a whole new branch of biomedical research has resulted: The study of the microbial community in a human intestine.

In the intestines, billions and billions of microbes, with colorful names like Bifidobacterium infantis and Lactobacillus acidophilus, live and function in a symbiotic relationship with each other, and with your own cells. Many of the critters that live in your gut cannot be grown in a laboratory test tube so their function, or even their existence, was unknown before genome sequencing. Now that scientists know what is there, they are discovering how important these bugs are in digesting our food, building our immune systems, maintaining stable glucose levels, and other jobs that are critically important to good health.

At the OSU College of Veterinary Medicine, in the Department of Biomedical Sciences, Natalia Shulzhenko is working on the frontier of this new science. Trained as a medical doctor, Shulzhenko became interested in the bugs that inhabit the gut while working at the National Institute of Health. One of her projects discovered a three-way interaction, or crosstalk, between the immune system, the intestinal lining, and intestinal bugs. When this communication was disrupted in mice, it led to poor absorption of fats and malnutrition. “We realized that what happens in the gut is not only about our own cells but about the microbes that live there. They have huge powers,” she says.

The crosstalk between human cells and microbes in the human intestines is also the focus of Shulzhenko’s current work investigating the possible connection between these microbes and Type 2 diabetes. This could not be done without two important tools provided by OSU. The first is the Center for Genome Research and Biocomputing (CGRB). “It is one of the reasons I chose to work at OSU,” says Shulzhenko. “They have a very strong genome center in terms of both machines and people.”

The CGRB recently installed a new high-throughput genome analyzer that significantly increases the speed of processing and, at the same time, brings the cost down. Analysis of a microbe that previously cost $10,000, now costs $1,000 and takes just a few days to complete. “We are now able to get much more information for the same amount of money,” says Shulzhenko.

The other tool that is vital to Shulzhenko’s work is her clan of germ-free mice that have been raised from birth in a sterile environment. They have no microbes in their guts and very few immune cells. They allow Shulzhenko to study bugs in a controlled environment. “We can introduce one specific microbe that we think is important, and look at exactly what it is doing,” she says.

The microbes in our intestines have many jobs. They keep harmful pathogens at bay; they play a role in the manufacture of enzymes, vitamins, and other essential nutrients; they produce signaling chemicals that regulate our appetite and digestion; and they influence the immune system.

“These are very complex communities,” says Shulzhenko. “Some of the microbes produce chemicals that are consumed by other microbes. So if you take an antibiotic that kills one of them, another may die too.”  Shulzhenko affirms the necessity of antibiotics to fight infectious disease but her work does illustrate the down side of their use. “Antibiotics are great but they cause effects on the microbes that can last for a long time, especially if you take them multiple times.”

The modern diet of high-fat, processed foods can also disrupt the complex community in our gut. It can cause inflammation of the intestines which inhibits the production of antibodies, proteins used by the immune system to identify and neutralize foreign bacteria. We need antibodies because they keep the microbe community under control.

Shulzhenko’s research on the crosstalk between metabolism and microbes showed that lack of antibodies can cause epithelial cells in the lining of the intestines to switch jobs: instead of efficiently processing glucose and other nutrients, under microbial pressure, they take over the immune functions of the missing antibodies.

If antibiotics and modern diet affect intestinal microbes, and disrupt the processing of glucose and other nutrients, it seems reasonable to suspect they are contributing factors to the development of Type 2 diabetes, and even obesity. “We don’t know for sure yet, but there are good indications of this from animal studies,” says Shulzhenko. She is looking at the genes of bugs that process nutrients to see what functions they perform and what happens when they get disrupted. “We also want to find bugs that would be beneficial and might decrease levels of glucose in diabetes and metabolic syndrome.”

All this new information about the vast network of microbes working away in your gut, has led to a boom in the probiotic supplement business. Microbes are being added to everything from yogurt to chocolate bars, and promoted for improving digestion and even preventing colds. But it’s not that simple. “We need to identify the ones that are really critical. That is the tricky part. It might not be specific species but rather what functions they perform,” says Shulzhenko.

Certainly most scientists are in agreement that a fast food diet and over-use of antibiotics have profound effects on the composition and diversity of the microbes in our guts. Researchers like Shulzhenko may someday discover an approach to restoring battered gut communities, but until then, skip McDonalds and eat your veggies.

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