Postbiotics May Prevent Diabetes in Obesity

You’ve likely heard about probiotics—live bacteria with long, colorful names found in your yogurt that help generate a happy gut. You may have even heard of prebiotics, which are compounds that have a beneficial effect on the bacteria in your body. But you’re probably less familiar with postbiotics—factors derived from bacteria that can also have a positive impact on our health.

Researchers at McMaster University who study diabetes and obesity have discovered a postbiotic factor called MDP that prevents pre-diabetic obese mice from developing diabetes. Their surprising results were recently published in Cell Metabolism.

When bacteria in the gut become chronically out of balance—known as intestinal dysbiosis [PDF]—a person can become insulin resistant, or prediabetic. Dysbiosis is often found in people with obesity. “Key markers on the road to diabetes are insulin sensitivity and insulin resistance—how well that hormone can lower blood glucose,” Jon Schertzer, lead study author and assistant professor of biochemistry at McMaster University tells Mental Floss. Insulin’s job is to bring your blood glucose back up to normal after you eat or drink something. If you’re insulin resistant, or improperly sensitive, insulin can’t do its job properly. “What a postbiotic does is allow the insulin to do a better job,” he says.

Schertzer’s team sought to investigate whether postbiotics could have an impact on obesity before a person becomes overtly diabetic. “The focus of this study is prediabetes—the stage before the overt disease has developed and it’s still reversible. Obesity is the biggest risk factor for prediabetes,” he explains.

The team found that a postbiotic called muramyl dipeptide (MDP), derived from a bacterial cell wall, was able to reduce insulin resistance in mouse models—regardless of weight loss or changes in the intestinal microbiome during obesity.

To test this, Schertzer separated mice into two groups. One group was given MDP at the same time as they were fed a high-fat diet intended to cause obesity. In that experiment, the mice were given MDP four days per week for five weeks. The MDP injections improved insulin and glucose tolerance after five weeks—remarkably, without altering body mass or fatty tissue levels.

In the second group, the team fed the mice into a state of obesity over 10 weeks, putting them into a state of prediabetes. Then they injected MDP into the mice three times over three days and saw a rapid improvement in blood glucose by the third day. “It’s not that the injection itself is lowering blood glucose, but those three short duration injections set the program up to allow insulin to work better,” he says.

When the body senses MDP is present, it increases the amount of a protein in fat tissue, called IR4, which sends out signals that lower blood glucose. “We don’t fully understand how it signals the body to lower blood glucose,” he admits. “We do know it reduces inflammation.”

While that may not sound dramatic, he says they were quite surprised, given that the typical immune response is to increase inflammation. “The postbiotic actually reduced inflammation in fat tissue, which are the tissues that control blood glucose,” he says.

While the results are exciting, he’s quick to point out that “we’re interested in discovery. We’ll leave the clinical aspect to clinicians.” They’d like to achieve a version of MDP that could be taken orally and not injected, but more research will be required. Plus, postbiotics can be a finicky area of research. He describes testing a different postbiotic that's a “a close cousin" to MDP, being "a different type of cell wall that was different by only one peptide.” But that postbiotic made glucose tolerance and inflammation much worse.

However, they also tested what’s called an “orphan drug”—approved only for clinical trials but not likely to make the drug company any money—called mifamurtide, typically used in treating bone cancers. Mifamurtide is synthetic, but chemically identical to the MDP postbiotic. It, too, improved blood glucose and insulin tolerance when administered to mice. The promising part about it is that since the drug is already given to humans in clinical trials, “it could make the transition to humans far more rapid,” he says.

One of their next steps is to expand the models they’re using, starting with age-induced diabetes. “Obesity is only one factor that promotes diabetes,” he says.

The most pressing question now, he says, is “to understand what is actually happening in the gut during obesity.” This compound promises a future in which obesity would pose less of a risk factor for diabetes. And postbiotics hold a lot of potential for future research.

“Postbiotics are a new source of drugs. Bacteria have different physiology from us, and can make all kinds of things that we can’t make,” Schertzer says.