Squeezing skinny genes into you

Project examines stool transplants to battle obesity

TORONTO • If you could lose weight by letting a doctor inject a skinny person’s poop into your intestine, would you consider it?

As the science linking gut bacteria with a litany of human diseases explodes, University of Toronto researchers are exploring human-tohuman stool transplants to combat obesity.

The team has just completed the first phase of a $1.5-million, federally funded project that might ultimately offer obese people an alternative to costly, risky and radical gut-reconfiguring weight-loss surgery.

Studies suggest people with obesity have different intestinal bacteria than those who don’t. Scientists believe different microorganisms living in the gut play a key role by acting on hormones that affect insulin sensitivity and the amount of calories absorbed from food.

The Toronto study comes on the heels of several animal studies showing that when germ-free mice — raised in ultra-sterile environments and free of intestinal bugs — are fed stool from obese mice, or obese humans, they put on more weight and body fat than those fed bacteria from the guts of lean mice or skinny humans.

As well, recent studies suggest bariatric surgery not only works by making it physically harder for people to overeat by reducing the size of the stomach, but also by altering the gut’s microbiome. It may explain why, soon after surgery, even before people start to shed weight, their blood-sugar levels improve dramatically.

Donor stool transplants are already proving effective in combating the hospital-acquired superbug C. difficile, while the “avantgarde” therapy is also being tested against ulcerative colitis and Crohn’s disease.

In a study of more than 1,500 healthy people published Monday in the journal Nature Genetics, Toronto researchers identified four key genetic markers that appear to be associated with changes in the gut microbiome. This suggests genes, and not just diet and environment, influence the makeup of the organisms in our guts.

“We have to look at these markers, what genes are they reflecting and how is it that a change in that gene has any influence on how gut bacteria occupy the gut,” said lead author Dr. Kenneth Croitoru, a clinicianscientist at Mount Sinai’s Zane Cohen Centre for Digestive Diseases in Toronto.

The obesity study is part of the University of Toronto Fecal Microbiota Transplantation Outcomes Program, which is looking for healthy donors, aged 18 to 50 (“We would love your poop for a research study,” says its website.)

The researchers are mapping changes in fecal bacteria in people before and after they undergo bariatric surgery.

“We chose the biggest guys — I mean BMIs of 50,” said Dr. Herbert Gaisano, a gastroenterologist and researcher at Toronto Western Hospital who, with U of T professor Dr. Johane Allard, is principal investigator in the study.

First, researchers took stool from the obese patients before surgery and fed it to germ-free, skinny mice “to see if the mice will either start gaining weight or increase insulin resistance,” Gaisano said.

Stool will be taken from the same patients after three and six months postop, and given to fat mice in the hope they won’t gain weight.

If the surgery alters the type and number of gut bacteria, “then we could potentially deploy (stool transplants) of that specific fecal flora to induce weight loss,” without people having to resort to surgery, Gaisano said.

The team will also explore whether stool from lean, healthy volunteers will improve blood sugar control and weight in the “morbidly” obese.

People will be randomly assigned to one of two groups: one group will receive stool from a carefully screened donor, the other his or her own stool (the “control group”).

Despite the promise of fecal transplants, the researchers are cautious. The field is moving so rapidly, “we haven’t learned to walk yet and we’re starting to run,” said Croitoru, who is also participating in the obesity study.

“Let’s be clear: this is not the cure to obesity nor is it the only cause of obesity. This is just an element of obesity.”