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It might be hard to recognize the value of human stool. After all, one of the words used to refer to it is "waste." However, stool might not only hold the key to better understanding obesity, but could also help find a way to treat it.
The study of stool has yielded improved options to treat diseases like Crohn's and infections like Clostridium difficile (C. diff). Based on those findings, a fast-growing area of research is focusing on stool and the naturally occurring bacteria in the gut that binds to it as a means to influence weight gain and weight loss.
In other words, can the gut bacteria of a thin person be transplanted into the gut of an obese person, via stool, and alter their gut bacteria in such a way that they will lose weight?
Dr. Herbert Gaisano, a gastroenterologist at Toronto Western Hospital (TWH), thinks that eventually, this could become a real possibility.
"This is a very exciting area of research that has a lot of potential," says Dr. Gaisano. "Through this work, we hope to identify the actual bug within the bacteria that causes obesity."
Understanding the microbiome
To do that, Dr. Gaisano and his team will be sorting through what's known as the gut's microbiome.
Microorganisms exist throughout the human body. Collectively, their genomes create an environmental niche specific to different parts of the body, called a microbiome. However, the genetic diversity that exists in the human microbiome is 100 times that of the human genome, meaning there are millions upon millions of bugs in the microbiome that are found in the gut.
"With all these bug possibilities, it is hard to figure out which one specifically effects change," says Dr. Gaisano. "But our research aims to find ways to prove the mechanism by which stool exchange can affect weight gain by studying bariatric surgery patients."
And that's where stool is invaluable.
Half of stool is made of bacteria that exist in the gut – bacteria that are specific to its individual. When non-digestibles enter the gut, the stool binds around it and it is excreted. Researchers have found that some bacteria can decrease the nutrient intake per unit of nutrient, meaning fewer calories are absorbed from food in the gut.
If researchers can isolate the bug within the bacteria that prevents this uptake, they can then possibly infuse stool with that bacteria, transplant it to obese patients where the bacteria will then multiply, and create an environment that decreases nutrient uptake and thereby prevents weight gain.
Identifying the bug
How will scientists find this bug?
To isolate the bug, or bacterial community, Dr. Gaisano and his co-principal investigator, Dr. Johane Allard, will lead a team of physicians, surgeons and basic scientists, to focus their research on bariatric patients with a Body Mass Index (BMI) of around 50.The research is being funded by a large team grant from the Canadian Institute for Health Research (CIHR).
Patients who undergo a specific bariatric surgical procedure called Roux-en-Y – in which a smaller stomach pouch is fashioned and then re-attached to a lower part of the small intestine to bypass a large part of the stomach and duodenum – experience immediate changes in their guts' microbiome post-surgery. This occurs because food is now bypassing the gut instead of being absorbed.
Before the patients undergo surgery, they will provide stool samples that will be transplanted to "germ-free" mice; mice who are free of microbiomes and specially developed for research. The first phase of the research will most likely show that those stool samples will make the mice gain weight.
"Previous research has shown that when you give stool samples from an obese mouse that possesses an 'obese' microbiome to germ-free mice in the same amounts of food intake, it makes them fat," says Dr. Gaisano. "So there is something specific to the bacteria that makes people overweight."
After the patients have surgery and the bacteria in the gut starts to change, they will continue to provide stool samples which will again be transplanted to germ-free mice. The researchers anticipate that the mice taking the post-bariatric surgery stool will be resistant to weight gain when fed a high-fat, high-caloric diet. Researchers will then analyze how the stool has changed from the first and second samples in an effort to isolate the bug or a change in the bacterial community.
"Essentially, trying to isolate this bug is like looking for a needle in a haystack," says Dr. Gaisano. "But by continuing to use the stool from the same patients, at least we are comparing it to the same 'haystack' again and again. This strategy gives us more confidenceto find that bug eventually."
Dr. Gaisano hopes to have some preliminary results in six months. If successful, stool transplants could become a treatment option for obese patients who don't want to undergo bariatric surgery.
Meaning that stool may one day be seen as anything but waste.