Akkermansia muciniphila is proving to be a superstar among microbes inhabiting the human gastrointestinal tract. Although it is currently commercially unavailable as a probiotic, Akkermansia has been hailed as being among emerging “second generation” probiotic organisms that yield unexpectedly substantial health effects. It is likely to become available either singly or as part of a collection of probiotic microbes near-future.
Humans are typically first exposed to this microbial species via breastfeeding, with 95% of adults harboring some proportion of Akkermansia. This unique miccroorganism, the only member of the Verrucomicrobia phylum of bacteria, is exceptionally responsive to its environmental conditions. In response to prebiotic fiber ingestion, for instance, it can increase 100-fold in number.
In experimental models, Akkermansia administration was associated with less weight gain on a weight gain diet, along with markedly less visceral fat accumulation. Much of the benefit is believed to be due to strengthening of the intestinal mucous lining and a reduction in metabolic endotoxemia, i.e., entry of bacterial lipopolysaccharide, LPS, into the bloodstream. LPS is a potent inflammatory toxin and keeping it at low levels in the bloodstream is a great advantage. Under normal circumstances, Akkermansia helps support the integrity of the intestinal mucous lining, both directly and by supporting the intestinal immune response and the health of other bacterial species—Akkermansia is what I call a “foundational species,” i.e., its activity supports to health and proliferation of other desirable bacterial species.
The Akkermansia population diminishes with aging. (The reduction in Akkermansia is just one among a landscape of changes in the microbiome with aging, such as proliferation of a few other mucous-consuming Bacteroides species and increasing dominance of Proteobacteria, a group that includes the Enterobacteriaeceae that comprise the organisms of SIBO. This is an issue I shall be discussing in future, as it is becoming clearer and clearer that a considerable portion of the phenomena of aging are due to SIBO and SIFO and may therefore be at least partially reversible.)
Other interesting observations include:
- Akkermansia is substantially reduced in number in people with psoriasis, inflammatory bowel disease, appendicitis, children who’ve received repeated courses of antibiotics, type 2 diabetes and pre-diabetes
- Akkermansia is enriched in slender people and athletes
- Akkermansia numbers diminish with a short-term (3-week) low-FODMAPs diet. This should come as no surprise, as FODMAPs are essentially the same as prebiotic fibers.
- Akkermansia increases substantially on a ketogenic diet and, along with Parabacteroides, may be responsible for the reduction in seizures achieved with ketosis
The totality of evidence, the majority of it observational and thereby inconclusive, suggests that, while Akkermansia can comprise anywhere from 0% to 5% of the total microbial population of the gut, maximum benefit occurs when it constitutes 4-5%.
A pilot clinical trial in humans was recently reported, however, in which participants with metabolic syndrome were administered 10 billion CFUs of Akkermansia per day for three months; compared to participants taking placebo, those receiving Akkermansia experienced 28% improved insulin sensitivity, 34% reduction in insulin levels, 5 pound weight loss, along with improvement in markers of liver function and inflammation, largely consistent with the observational evidence. Should these effects be corroborated, this is huge, as it means that replenishment of this one microorganism provides benefits that exceed that achieved with the silly drugs for type 2 diabetes achieved without the huge side-effects, hypoglycemia, and costs of prescription drugs.
Unlike most other gut bacteria that obtain much of their nutrition from prebiotic fibers, Akkermansia has been shown to be stimulated to proliferate by some unusual factors, as well as by prebiotic fibers. Factors, foods, and strategies that have been shown to increase the population of Akkermansia in the intestinal tract include:
- Fructooligosaccharides, FOS–An especially powerful trigger for Akkermansia, increasing its growth as much as one thousand-fold. (Inulin likely has a similar effect, though this has not been formally studied.) FOS are likely the “preferred” energy source for Akkermansia, as it is more vigorously consumed than any other potential nutrient.
- Metformin–This drug commonly used as first-line treatment of type 2 diabetes increases Akkermansia and reduces lipopolysaccharide entry into the bloodstream, thereby reducing inflammation.
- Various flavonoids/polyphenols–Black tea, red wine/Concord grape juice, and rhubarb increase the Akkermansia population.
But, like many other good things, too much of a good thing may also be bad. It’s name–“muciniphila” means mucous-lover—referring to its unique capacity to also feed on the mucous lining of the intestine. When deprived of prebiotic fibers, for example, Akkermansia will survive by overconsuming the mucous lining of the intestinal tract, thinning it to almost nothing, a survival advantage that most other bacteria lack. In this situation, there is a marked reduction in the numbers of non-mucous consuming species, a reduction in species diversity, as well as more-than-usual proliferation of Akkermansia. Degradation of the mucous lining, whether achieved by synthetic emulsifying agents such as polysorbate 80 or hydroxymethcylcellulose, deprivation of prebiotic fibers, or over-proliferation of Akkermansia, has been associated with inflammation of the intestines, increased LPS entry into the bloodstream, autoimmune conditions, neurodegenerative conditions such as multiple sclerosis and cancers.
I don’t believe that we have to obsess over managing the precise proportion of Akkermansia in our guts, but I believe it is a powerful reminder that prebiotic fibers, consumed every day, are a critical component of an overall health effort, including not allow Akkermansia to convert from friend to foe.