From Dr. Lauren Deville - Naturopathic Doctor

Image by A M Hasan Nasim from Pixabay

Semaglutide in all its various permutations (Ozempic, Wegovy) are all the rage for weight loss at the moment. They work by activating the glucagon-like-peptide-1 (GLP-1) receptor, which in turn increases a sense of satiety by delaying gastric emptying, as well as increasing insulin secretion, which in turn means glucose levels drop.

I’ll tell you right now that I won’t prescribe it—not only does it carry a black box warning for increased thyroid cancer risk, but it’s also associated with kidney injury, pancreatitis, gallstones and gallbladder inflammation, as well as (given the delayed gastric emptying effect), gastroparesis. Most drugs have a long potential side effect list, of course, but if you look at the cost/benefit analysis, the math on this one just doesn’t make sense to me.

That said, there’s a fairly recently discovered probiotic that might have at least a similar mechanism of action, without the nasty side effect profile. It’s called Akkermansia—and there might be some other reasons to consider it, too.

What Akkermansia IsAkkermansia is an anaerobic bacteria that nevertheless tolerates oxygen, as it encounters plenty of it in its environment in the intestinal mucus layer.

Like most probiotics, it eats prebiotics, so those foods help to boost the population.

It’s abundant, accounting for 1-3% of the microbiome, though variation in these percentages correspond to various disease states.

Akkermansia and GLP-1Intestinal cells secrete peptide hormones in response to intestinal contents, signaling the brain that we’re full and it’s time to stop eating. One of these is glucagon-like peptide-1 (GLP-1). As mentioned above, GLP-1 delays gastric emptying and also stimulates the pancreas to release more insulin—on the assumption that we’ve just consumed a big meal (that after all is what’s supposed to trigger its release) and we’ll need the insulin in order to metabolize the glucose.

GLP-1 also triggers the body’s AMPK pathway, which causes the body to burn energy as heat, rather than store it.

It turns out that Akkermansia regulates GLP-1 by producing a protein that triggers a cascade of events that ultimately leads to GLP-1 production.

Akkermansia and Metabolic Syndrome This may not be the only mechanism by which Akkermansia supports metabolism. It’s also been shown to significantly reduce inflammatory cytokine production in adipose tissue. Since fat is hormonally active, and inflammation tends to perpetuate adiposity, this may be another way in which it helps.

Fatty liver (NAFLD) is nearly always connected to insulin resistance, and Akkermansia also was shown in this mouse study to help reverse fatty liver and associated liver inflammation and injury.

Akkermansia and Leaky Gut Akkermansia also has been shown to help maintain a healthy gut barrier and heal intestinal permeability, possibly via the endocannabinoid system as well as gut peptide modulation.

It also increases production of the mucus layer, which likewise acts to protect the gut barrier.

Akkermansia and Gut Inflammation—Good or Bad?There are a few caveats, though—it’s possible for there to be too much of a good thing.

While some studies suggest that Akkermansia decreases inflammation in IBD such as Crohn’s or Ulcerative Colitis, as implied by the gut barrier protective mechanisms, and that they increase butyrate production (one of the primary Short Chain Fatty Acids that keep the gut healthy), this study showed that Akkermansia given to otherwise germ-free mice actually increased intestinal inflammation, compared to bacteria in the bacteroides family, which did not have the same effect.

I suspect this can best be understood in the context of balance. While neither bacteroides nor akkermansia make up the bulk of overall normal gut species, the former is expected to be a significantly higher percentage of the pie than the latter. A little bit of akkermansia may be anti-inflammatory, while a lot (as in a case of introducing a single species to an otherwise sterile gut) may have the opposite effect. This is likely hormesis in action. In the same way, we’re all supposed to have some clostridia in our guts, and that’s quite normal (it’s in the firmicutes family, associated with weight management and balance, as well). But if too much of the rest of the microbiome gets wiped out with some heavy duty antibiotics, that’s when we might end up with “C. diff”—which can be very serious if it’s out of control. Yeast is the same way—we should have some yeast in our guts. That’s normal. Problems occur when we have a yeast overgrowth.

This may also (at least partly) explain why this study shows that patients with Parkinson’s and Multiple Sclerosis tend to have more Akkermansia as part of their microbiome than the rest of the population. This doesn’t necessarily imply a causal link between the bacteria and the diseases (it might, but I doubt it. We’d need more research to establish this for sure). Rather, I think it’s more likely this suggests an overall gut flora imbalance as part of the disease process. There’s possibly a lack of some other good flora and akkermansia simply fills the void–and maybe all of this is secondary to some other, deeper cause.

It wouldn’t make sense for those who already have an overabundance of a given organism to take more of it, though.

The UpshotThis 2020 randomized controlled trial established the safety of akkermansia as a supplement, albeit with only 76 people. It also demonstrated that the organism indeed did help to regulate glucose levels, which is why it is now available for purchase commercially, as an alternative approach to GLP-1 mediated weight management. (Definitely better than the currently trending alternative!)

Akkermansia, GLP-1, and Weight Loss