02. Olanzapine-Induced Weight Gain: Can Akkermansia Muciniphila Help?

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The Potential of Probiotics in Psychiatric Treatment

I am going to discuss what I think is an interesting topic in an emerging therapeutic area, the issue of probiotics as a treatment in Psychiatry.

The International Scientific Association for Probiotics and Prebiotics defines probiotics as live microorganisms that when administered in adequate amounts confer a health benefit on the host. You probably recognize probiotic products like lactobacillus or bifidobacterium.

Akkermansia Muciniphila: A Possible Weight Gain Solution?

The publication that caught my eye was a review titled, “A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain.” It was written by a colleague from Trieste in Italy, Dr. Francesca Bertossi, and published in the open access journal, Cureus.

Now, I admit that I had never heard of Akkermansia muciniphila but I treat a lot of people with antipsychotics including olanzapine. And as most of you will know, olanzapine together with clozapine are the two metabolically most problematic antipsychotics.

So naturally, I was curious:

• What is this Akkermansia muciniphila?
• Could I actually give it to my olanzapine-treated patients to help with their weight gain?

Discovering the Importance of Akkermansia Muciniphila

This is what I learned from the review and some ancillary readings that I did. Some of you may have guessed correctly that Akkermansia muciniphila is a bacterium.

It was only discovered about 20 years ago and it is named after a microbial ecologist from the Netherlands by the name of Anton Akkermans and after its mucin-loving properties, hence muciniphila.

This bacterium is very important for healthy gut function even though it only makes up 5% of the microbiota. So it functions as a so-called keystone species.

Keystone Species and Their Role

A keystone species is a species that has a disproportionately large effect on an ecosystem relative to its low numbers. If you remove a keystone species, the whole system can potentially collapse if there’s not redundancy in the system to replace this keystone species.

So Akkermansia is in the minority in a normal gut but very important for gut functioning.

The Critical Role of Akkermansia in Gut Health

So why may Akkermansia be so critical for a healthy gut despite being in this minority? Now, it has to do with its, as the name implies, predilection or love of mucin.

You may remember from basic histology in medical school that the epithelial cells that line the lumen of the GI tract are covered by mucin or slime together forming the barrier between the lumen of the GI tract and the interior of the human body.

Now, Akkermansia is a critical bacterium that keeps this mucin barrier functioning and healthy by degrading mucin and thus allowing the mucin-producing goblet cells to replenish old mucin and in that way preventing and increasing gut permeability.

The Consequences of Increased Gut Permeability

You may know vaguely at least that pathologically increased gut permeability has been associated with a wide variety of responses by the human organism such as immune activation which may then contribute to psychosomatic illnesses like irritable bowel syndrome or immune problems like atopic dermatitis.

Akkermansia also has been shown to increase GLP-1 production, which you may recognize from the newer class of weight loss medications that are GLP-1 agonists like semaglutide.

Antipsychotics, Microbiota Changes, and Weight Gain

As I learned from this review, medications like antipsychotics change the composition of the microbiota in ways that contribute to weight gain, for example, by changing the signaling from the gut to the central nervous system about food intake and satiety.

There have also been studies showing directly associations between our bacterium of interest, Akkermansia, and metabolic problems. One study, for example, showed that Akkermansia is reduced in bipolar patients treated with second-generation antipsychotics treated with olanzapine.

There even has now been one randomized controlled trial of 40 obese or overweight patients that showed good benefit for patients when given Akkermansia, benefit on several metabolic parameters.

Finally, the review points out that metformin that we often use clinically together with olanzapine affects the microbiota by increasing Akkermansia.

Isn’t that interesting?

The Availability and Legitimacy of Akkermansia Supplements

So can you buy Akkermansia? Yes, you can. I looked on the internet and Akkermansia is available as a probiotic supplement and importantly Akkermansia, at least where I looked, seems to be sold by a legitimate source.

This is not irrelevant if people want to try supplements which are regulated by the FDA but they don’t go through the same approval process that medications undergo or a company has to show not just efficacy but also safety.

The Decision to Recommend Akkermansia Supplements

Should you actually recommend that your patient buys Akkermansia muciniphila probiotic supplements? I’m still on the fence about that given that it’s not cheap and at least in the United States it will not be covered by insurance. So people have to pay out of pocket.

We also have a good and well-established intervention for metabolic prevention in the form of metformin that I use routinely in my patients on olanzapine.

The Plausibility and Support for Akkermansia’s Therapeutic Benefit

On the other hand, after reading this review, I was intrigued. The idea of correcting so-called dysbiosis, an imbalance of the gut microbiota, if you will, is at least one contributing factor in medication-associated weight gain has biological plausibility.

And in addition, Akkermansia specifically has support from both animal and clinical research that it may have therapeutic benefit for patients treated with antipsychotics.

A Holistic Approach to Patient Preferences

Let me add this thought. I have a lot of patients who want to try more natural remedies and who would rather not take another medication like metformin to manage their metabolic problems associated with antipsychotics.

In a more holistic treatment paradigm regarding managing your weight, a probiotic supplement fits perhaps more naturally particularly if your patient can combine it with other health interventions like exercise and eating well.

And at a minimum, you should have some educated opinion about this issue since patients may read about Akkermansia and ask you about it.

The Bottom Line

Probiotics are interesting supplements for Psychiatry given the connection between the gut or the enteric nervous system and the central nervous system.

The keystone species Akkermansia muciniphila may indeed be, as one mini review titled it, a next generation beneficial microbe specifically to manage weight gain associated with psychotropics.

But stay tuned and look for more studies in the future in this I think interesting area.

Abstract

A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain

Francesca Bertossi, M.D.

Second-generation antipsychotics are mainly used in both acute and long-term treatment of major psychiatric disorders. Although better tolerated than first-generation antipsychotic drugs, they can frequently induce weight gain and metabolic disorders, of these, olanzapine is one of the drugs more likely to induce these side effects. There is consistent evidence of the role of gut microbiota in modulating the gut-brain axis with complex crosstalk with the host involving satiety signaling pathways, food intake behavior, and weight and metabolic regulation. Second-generation antipsychotics induce important gut microbiota modification thus contributing together with the central and peripheral receptors blockade mechanism to weight gain induction and metabolic impairment. These drugs can alter the composition of gut microbiota and induce dysbiosis, often reducing the concentration of Akkermansia muciniphila, a bacterium that is also decreased in patients with diabetes, obesity, metabolic syndrome, or chronic inflammatory diseases. Probiotic administration can be a safe and well-tolerated approach to modulate microbiota and offer an integrative strategy in psychiatric patients suffering antipsychotic side effects. Multiple strain probiotics and Akkermansia muciniphila alone have been administered both in mice models and in clinical populations demonstrating efficacy on antipsychotic-induced metabolic impairment and showing a contribution in reducing induced weight gain. Akkermansia muciniphila can improve several parameters altered by olanzapine administration, such as weight gain, insulin resistance, hyperglycemia, liver function, systemic inflammation, and gut barrier function. Although we do not have jet trials in the psychiatric population, this probiotic may be a complementary approach to treating olanzapine-induced weight gain and metabolic side effects.

Keywords: akkermansia muciniphila; antipsychotic-induced weight gain; gut microbiota; gut-brain axis; inflammation; metabolic syndrome; olanzapine.

Reference

Bertossi, F. M.D. A Possible Role of Akkermansia muciniphila in the Treatment of Olanzapine-Induced Weight Gain. (2024). Cureus.