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.

Why Thousands of 'Penis Fish' Washed Up on a California Beach

Kate Montana, iNaturalist // CC BY-NC 4.0
Kate Montana, iNaturalist // CC BY-NC 4.0

Nature works in mysterious ways. The latest example materialized at Drakes Beach near San Francisco, California, in early December, when visitors strolling along the shore stumbled upon what looked to be the discarded inventory of an adult novelty shop. In fact, it was thousands of Urechis caupo, a marine worm that bears more than a passing resemblance to a human penis.

The engorged pink invertebrate, which is typically 10 inches in length, is native to the Pacific coast and frequently goes by the less salacious name of “fat innkeeper worm.” Burrowing in sand, the worm produces mucus from its front end to ensnare plankton and other snacks, then pumps water to create a vacuum where the food is directed into their tunnel. Since it builds up a small nest of discarded food, other creatures like crabs will stop by to feed, hence the “innkeeper” label.

You can see the worm in "action" here:

Because the worms enjoy a reclusive life in their burrows, it’s unusual to see thousands stranded on the beach. It’s likely that a strong storm broke up the intertidal sand, decimating their homes and leaving them exposed. The event is likely to thrill otters, as they enjoy dining on the worm. So do humans: Penis fish are served both raw and cooked in Korea and China.

[h/t Live Science]

The Horrors of Anglerfish Mating

Masaki Miya et al. "Evolutionary history of anglerfishes (Teleostei: Lophiiformes): a mitogenomic perspective," BMC Evolutionary Biology 10, article number: 58 (2010), Wikimedia Commons // CC BY 2.0
Masaki Miya et al. "Evolutionary history of anglerfishes (Teleostei: Lophiiformes): a mitogenomic perspective," BMC Evolutionary Biology 10, article number: 58 (2010), Wikimedia Commons // CC BY 2.0

When you think of an anglerfish, you probably think of something like the creature above: Big mouth. Gnarly teeth. Lure bobbing from its head. Endless nightmares. 

During the 19th century, when scientists began to discover, describe, and classify anglerfish from a particular branch of the anglerfish family tree—the suborder Ceratioidei—that’s what they thought of, too. The problem was that they were only seeing half the picture. The specimens that they were working with were all female, and they had no idea where the males were or what they looked like. Researchers sometimes found some other fish that seemed to be related based on their body structure, but they lacked the fearsome maw and lure typical of ceratioids and were much smaller—sometimes only as long as 6 or 7 millimeters—and got placed into separate taxonomic groups.

It wasn’t until the 1920s—almost a full century after the first ceratioid was entered into the scientific record—that things started to become a little clearer. In 1922, Icelandic biologist Bjarni Saemundsson discovered a female ceratioid with two of these smaller fish attached to her belly by their snouts. He assumed it was a mother and her babies, but was puzzled by the arrangement.

“I can form no idea of how, or when, the larvae, or young, become attached to the mother. I cannot believe that the male fastens the egg to the female,” he wrote. “This remains a puzzle for some future researchers to solve.”

When Saemundsson kicked the problem down the road, it was Charles Tate Regan, working at the British Museum of Natural History in 1924, who picked it up. Regan also found a smaller fish attached to a female ceratioid. When he dissected it, he realized it wasn’t a different species or the female angler’s child. It was her mate.

The “missing” males had been there all along, just unrecognized and misclassified, and Regan and other scientists, like Norwegian zoologist Albert Eide Parr, soon figured out why the male ceratioids looked so different. They don’t need lures or big mouths and teeth because they don’t hunt, and they don’t hunt because they have the females. The ceratioid male, Regan wrote, is “merely an appendage of the female, and entirely dependent on her for nutrition.” In other words, a parasite.

When ceratioid males go looking for love, they follow a species-specific pheromone to a female, who will often aid their search further by flashing her bioluminescent lure. Once the male finds a suitable mate, he bites into her belly and latches on until his body fuses with hers. Their skin joins together, and so do their blood vessels, which allows the male to take all the nutrients he needs from his host/mate’s blood. The two fish essentially become one.

With his body attached to hers like this, the male doesn't have to trouble himself with things like seeing or swimming or eating like a normal fish. The body parts he doesn’t need anymore—eyes, fins, and some internal organs—atrophy, degenerate, and wither away, until he’s little more than a lump of flesh hanging from the female, taking food from her and providing sperm whenever she’s ready to spawn.

Extreme size differences between the sexes and parasitic mating aren’t found in all anglerfish. Throughout the other suborders, there are males that are free-swimming their whole lives, that can hunt on their own and that only attach to the females temporarily to reproduce before moving along. For deep-sea ceratioids that might only rarely bump into each other in the abyss, though, the weird mating ritual is a necessary adaptation to keep mates close at hand and ensure that there will always be more little anglerfish. And for us, it’s something to both marvel and cringe at, a reminder that the natural world is often as strange as any fiction we can imagine.

Naturalist William Beebe put it nicely in 1938, writing, “But to be driven by impelling odor headlong upon a mate so gigantic, in such immense and forbidding darkness, and willfully eat a hole in her soft side, to feel the gradually increasing transfusion of her blood through one’s veins, to lose everything that marked one as other than a worm, to become a brainless, senseless thing that was a fish—this is sheer fiction, beyond all belief unless we have seen the proof of it.”

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