No doubt there are many who dismiss the idea that the gut microbiome has a role to play in the management of advanced PCa, but the Akkermansia muciniphila story is fascinating, so stay with me.
My interest in Akkermansia is recent & triggered by the midnight research of an industrious Swedish member.
1] Sep 2020, Canada:
Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
"Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila."
"... Akkermansia muciniphila, appears to be particularly important for positive response to anti-PD-1-based immunotherapies"
"This species has also been inversely correlated with inflammation, obesity, and a variety of metabolic disorders in mice and humans ..."
Sometimes it seems to me that PCa is just another of the symptoms associated with the metabolic syndrome [MetS]. Certainly, men with PCa are more at risk for MetS-related cardiovascular events. And ADT induces MetS, if not diabetes, in men with PCa. The idea that Akkermansia might counter Mets is intriguing.
"The seminal findings that steroidal progesterone derivate AA could inhibit CYP17A and thereby improve PC patient outcome in castrate-resistant cohorts has led to the widely accepted consensus that castrate-resistant PC remains a hormonally driven process. Our results suggest that the efficacy of AA may be imparted through its ability to increase microbially synthesized vitamin K2 in PC patients via specific interactions with the key symbiont, A. muciniphila. Altogether, these findings expand on previous work from several other large studies that have demonstrated A. muciniphila to invoke a multiplicity of health benefits in their hosts and improve the efficacy of checkpoint inhibitor cancer immunotherapies"
2] 2018, Johns Hopkins:
This study reported that that oral androgen receptor axis-targeted therapies (ATT), including bicalutamide, enzalutamide, and abiraterone acetate, resulted in "a greater abundance of species previously linked to response to anti-PD-1 immunotherapy such as Akkermansia muciniphila and Ruminococcaceae spp."
3] see also Apr 2021, China:
Extracellular Vesicles from Akkermansia muciniphila Elicit Antitumor Immunity Against Prostate Cancer via Modulation of CD8+ T Cells and Macrophages
"Akk, an important commensal bacterium in the gut microbiota, is now widely investigated and considered a potential next–generation probiotic. Recent studies have found that the reduction of Akk content in the gut is associated with various disease conditions. Supplementation with this bacterium can facilitate treatment of many metabolic and immune disorders, including obesity, inflammatory bowel disease, type 2 diabetes, and atherosclerosis. Remarkably, Akk has also been reported to impact cancer immunotherapy."
Interesting stuff. The gut biome is such a complicated ecosystem. I think a better understanding of it in the future will lead to dietary and drug interventions that slow disease progression by way of beneficial change to the microbiome.
A year or so back when I showed my then MD Anderson MO the Swedish article in Nature about Dukoral his comment was anything that improves your gut biome may have a beneficial impact on PCa, simply because it makes one healthier...
Akkermansia thrives on polyphenols such as those from pomegranate, blueberry and concord grape. Concentrated juices can be diluted with water. Unsweetened of course.
Since I live in Sweden it is very (!) expensive, and difficult, to get a hold on. Yet if there is Akkermansia to get a hold on for my father, I'm willing to try. Thankful for any thoughts!
Microbiome Labs Mega Sporebiotic - probiotic was recommended to us. I am not sure if it has the best probiotics in it but it is supposed to be effective . It is available on Amazon but I buy from sanjevanistore dot com. I am concerned about the counterfeit products on Amazon.. and I know Sanjevani is a valid supplier. I am sure there are others valid suppliers. Prayers for you all!
The problem I have with it is that there should have been an arm that received inulin alone.
Inulin is simply a fiber (from chickory, artichokes, agave, etc.) that passes through to the gut, where it may act as fuel to friendly bacteria. It is a pro-biotic and does not add bacteria to the diet. Would some of the participants benefited from inulin alone? Worth a try - I have some on order:
The evidence suggests that, to increase Akkermansia in the gut, you can add some things and you can subtract some things. Among the factors to consider:
Add:
Prebiotics–especially inulin/FOS that markedly amplifies Akkermansia growth, up to 100-fold in experimental models.
Polyphenols–These are the red-, purple-, orange-colored vegetables and fruits that, for not entirely clear reasons, encourage Akkermansia growth. Especially potent stimuli include cranberries, grapes, and pomegranate. (Red wine is uncertain: While rich in polyphenols, the ethanol reduces Akkermansia and the net effect–increase or decrease–remains unclear.)
Green tea–The epigallocatechins of green tea, like the polyphenols of veggies and fruit, also encourage Akkermansia.
Subtract:
Grains and sugars–i.e., the components of a high-carb diet. Low-carb diets therefore increase Akkermansia, as with the ketogenic diet. (The arabinoxylan and amylose of grains, however, also stimulate Akkermansia; but, of course, grains come with so much other unhealthy baggage—the presence of these two prebiotic fibers is insufficient to justify their inclusion.)
Excess weight–Weight loss from obese or overweight levels increase Akkermansia.
I came across an article as I was researching the probability of bone mets at low PSA and thought that it might be something that would interest you. Found this post when I searched for "extracellular vesicles" and decided to post the link to it here.
Emerging Players in Prostate Cancer–Bone Niche Communication
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