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What's with this "GLP-1 Probiotic"?

Updated: May 1

I’m not recommending for or against this specific probiotic but I wanted to remember it so I made a mascot. I like the concept of a probiotic for which it doesn’t seem to matter whether the bacteria are alive or not. It was brought to my attention because anecdotally it decreases cravings for sweets and it was proposed as an adjunct to olanzapine.

Akkermansia muciniphila 

Mascot: "Mucin-loving Anchorman"

Akkermansia muciniphila is a gram-negative anaerobic bacterium found in the GI tract in about 90% of humans,  It lives off of mucin secreted by the GI tract and produces short-chain fatty acids (SCFAs) involved in appetite signaling. It is branded as the “GLP-1 probiotic” because it allegedly induces production of GLP-1 which would theoretically reduce appetite like a GLP-1 agonist, e.g., semaglutide (Ozempic). 

The gut communicates with the brain via the vagus nerve and through inflammatory cytokines. There is consistent evidence concerning the role of gut microbiota in balanced weight through the gut-brain axis (Cryan JF et al, 2019). In rats, olanzapine negatively affects gut microbiota (Davey KJ et al, 2012). 

Although it has not been tested in the psychiatric population, A. muciniphila has been proposed as an adjunct to olanzapine (Zyprexa) to ameliorate weight gain and metabolic side effects (Bertossi, 2024).

Experimental evidence points to obesity as transmissible via fecal microbiota transplantation (Turnbaugh et al, 2008). As a side note, fecal transplant appeared to reduce alcohol cravings (Bajaj et al, 2020). 

The administration of A. muciniphila to humans was first investigated by RCT in 2019 by Depommier, et al.  Daily oral supplementation of pasteurized A. muciniphila improved insulin sensitivity, reduced insulinemia, reduced plasma cholesterol, decreased body weight by ~ 2 kg and hip circumference by ~ 2cm.  

How could a pasteurized probiotic possibly work? Plovier et al (2016) discovered serendipitously  that pasteurization of A. muciniphila did not impair (and possibly enhanced?) its capacity to reduce fat development, insulin resistance, and dyslipidemia in mice. They demonstrated that a specific protein (Amuc_1100) isolated from the bacteria provided partial benefit, possibly by interacting with Toll-like receptor 2. 

A RCT of probiotics (available in China) in patients with schizophrenia taking olanzapine attenuated insulin resistance. Adding fiber to the probiotic resulted in only a 5 kg gain compared to 9 kg on olanzapine + placebo (Huang J et al, 2022). Probiotics are thought to work better when taken with a prebiotic such as dietary fiber to nurture the bacteria. 

Probiotic brand suggestions

The probiotic mixture VSL#3 reversed olanzapine-Induced metabolic dysfunction in mice (Dhaliwal et al, 2019).  It is available on Amazon as VSL#3 Medical Food for Gut Health, although pricey at $130 for 60 caps, which is a 1 or 2 month supply. VSL#3 does not contain Akkermansia muciniphila.

A reputable product that contains bacterial strains with mental health benefits, contains a prebiotic, and is available for $14/month on Amazon is Nature’s Way Fortify Daily Probiotic + Prebiotic.  It does not contain Akkermansia muciniphila.

Update 4/25/24: After speaking with several other physicians, I can say that if a probiotic containing Akkermansia muciniphila is wanted, Pendulum is the brand. The products are "Metabolic Daily with Akkermansia" or "Akkermansia Probiotic with Prebiotic Fiber", which are about $55/mo on Amazon.

Update 5/1/24: Pendulum offers higher dose products that are available (only?) through integrative medicine physicians offices, Metabolic Daily Pro and Akkermansia 500 Pro, usually for about $65 to $70 monthly. Slightly more expensive but a lot more bacteria.

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