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The gut microbiome constitutes a vast array of bacteria, fungi, and viruses that play key roles in digestion, immune system regulation, body weight management, and more. Among the over 5,000 different types of bacteria present in the gut is a species known as Akkermansia muciniphila.
Akkermansia muciniphila is a Gram-negative, anaerobic (thrives in low-oxygen environments) bacteria that lives in the mucus layer of the colon. It is one of the most abundant bacteria in the gut microbiome, constituting up to 5% of the total bacteria in the gut in healthy adults.
Akkermansia are found in both the adult and infant gut. Interestingly, Akkermansia are present in colostrum and breast milk. Their consumption during infancy seeds the infant gut with these beneficial bugs.
In addition to feeding on mucus proteins, Akkermansia populations are also supported by key prebiotics. Prebiotics are molecules that pass through our digestive systems intact and reach to the colon where they can support the growth of beneficial microbes. The prebiotics that promote Akkermansia growth include polyphenols and human milk oligosaccharides (HMOs).
Polyphenols are antioxidant molecules found in a variety of foods, and can often be identified by their vibrant colors. For example, the dark purple-blue pigments found in blueberries, blackberries, cranberries, and red cabbage are a group of polyphenols known as anthocyanins.
Polyphenols have the ability to neutralize free radicals and, in doing so, protect against oxidative stress and inflammation.
In addition to their direct anti-inflammatory effects, polyphenols can also feed Akkermansia and another important group of bacteria in the gut known as Bifidobacteria. Therefore, polyphenol consumption can support the colonization of the gut by these two key groups of bacteria.
In addition to polyphenols, HMOs are another crucial substrate supporting the health of the microbiome. HMOs, like 2’-fucosyllactose, are indigestible carbohydrate molecules first identified in human breast milk whose purpose is to facilitate microbial colonization of the gut in infants.
There have been over 200 different HMOs identified, over 100 of which have been formally characterized. The type and abundance of HMOs present in a mother’s breast milk is dependent upon what forms of the FUT2 gene she possesses.
It is well-established that HMOs are particularly adept at supporting the growth and colonization of Bifidobacteria in the gut. In fact, the infant gut comprises up to 90% Bifidobacteria for this very reason.
Emerging evidence suggests that Akkermansia are also capable of consuming HMOs as a food source. Indeed, the enzymes that Akkermansia use to break down the glycoproteins in mucus are capable of directly breaking down certain HMOs. Interestingly, many subspecies of Akkermansia muciniphila only feast on a portion of the HMO molecule, releasing the rest into their surroundings to be consumed by other beneficial bacteria.
Figure 1 Akkermansia muciniphila growth in human milk or porcine mucin as the sole carbon and nitrogen source.
In this way, supplementation with HMOs like 2’-fucosyllactose directly bolsters populations of Bifidobacteria and Akkermansia while indirectly supporting the growth of other microbes in the gut, thereby promoting microbial diversity.
Fructooligosaccharides (FOS)
Fructooligosaccharides (FOS) are chains of fructose molecules linked together that serve as a food source for bacteria in the colon. FOS are found in foods such as onion, asparagus, banana, and artichoke.
Although there have not yet been studies looking at the effects of FOS consumption on Akkermansia populations in humans, multiple animal studies have shown that FOS can increase levels of Akkermansia especially in models of obesity and diabetes.
Moreover, FOS consumption was linked to reduced fat mass, decreased gut permeability, and enhanced blood sugar control in these models. These benefits were attributed to the enhancements in Akkermansia levels in response to FOS feeding.
Berberine is a plant alkaloid that stimulates pathways in the body associated with fasting, making it a fasting mimetic. It has proven benefits on metabolic health, including lipid-lowering and anti-obesity effects, and improved glucose control.
Studies conducted in rodent models suggest that berberine is extremely effective at bolstering levels of Akkermansia in the gut in a dose-dependent manner, and that this effect is likely partially responsible for its health benefits.
Although these results have not yet been recapitulated in humans, the metabolic benefits of berberine are consistent across rodents and humans, which suggests that the effects on Akkermansia may also be conserved.
In addition to dietary and lifestyle strategies, research efforts are also geared towards determining whether Akkermansia probiotics could confer benefits to human health.
Although there is a dearth of research examining the effects of Akkermansia probiotics in humans, several studies have been conducted in animal models of diet-induced obesity.
Rodent models of diet-induced obesity (DIO) fed a high fat, high sugar diet mimicking a Standard American Diet exhibit suppressed populations of Akkermansia and develop similar conditions as human with diet-induced obesity including systemic inflammation, arterial plaque, breakdown of the gut mucus layer, and insulin resistance.
Upon four to eight weeks of treatment with an Akkermansia probiotic, DIO mice exhibit restored levels of Akkermansia as measured in fecal samples, with no other changes to the microbiome composition.
Additionally, these animals showed reduced levels of inflammation, shrinking of plaques, restored gut mucus layer thickness, reduced body weight, and improved insulin sensitivity.
However, these benefits were only seen with the higher dose probiotic not the lower dose suggesting that dosing may be an important consideration when using Akkermansia probiotics in the setting of obesity and metabolic dysfunction in humans.
In other animal studies, researchers supplemented DIO rodents with a probiotic containing Bifidobacterium animalis (subspecies lactis) to see if bolstering the levels of this species in the gut could indirectly boost levels of Akkermansia.
Indeed, treatment of the animals with this species for 14 weeks resulted in a dramatic increase in the fecal content of A. muciniphila. The group treated with this probiotic also gained less weight than control animals also fed the high fat, high sugar diet.
The mechanism by which B. animalis promotes the growth of A. muciniphila is still unknown, however the researchers postulate that it may be due to enhanced butyrate production facilitated by B. animalis, as butyrate stimulates mucus production in the gut.
What are Postbiotics? In addition to supplementation with Akkermansia probiotics, the use of Akkermansia postbiotics is another area that shows a great deal of promise. A postbiotic, also known as a ghost probiotic or para-probiotic, consists of either dead or inactivated bacteria or a bacterial extract that promotes health upon consumption.
Benefits: In rodent models, the administration of a pasteurized Akkermansia postbiotic actually resulted in even more beneficial effects than a live Akkermansia probiotic in normal, healthy mice. The mice given the postbiotic showed greater improvements in their lipid profiles, glucose control, liver enzymes, and immune markers than those animals given the live probiotic.
Pros of Using Postbiotics: The potential efficacy of postbiotics is particularly encouraging given that live probiotics can carry risks including small intestinal bacterial overgrowth (SIBO) as well as infection in immunocompromised individuals, infants, and the elderly.
In addition to dietary interventions to increase Akkermansia, there are also lifestyle modifications that can support levels of these important bacteria in the gut.
Intermittent fasting (IF) is the restriction of food intake to a defined window of time during the day. Some examples of IF include 12:12 and 16:8, where 12:12 is fasting for 12 hours and feeding within a 12 hour window and 16:8 is fasting for 16 hours and feeding within an 8 hour window.
Research on the effects of Islamic fasting (i.e. 17-hour fasting window, 7-hour feeding window) showed that 29 days of this IF strategy resulted in a significant increase in the levels of Akkermansia in the gut.
In another study, Akkermansia abundance was also elevated in individuals who participated in a five-day therapeutic fast wherein only water, tea, fruit juices, and broths were consumed.
It’s worth noting that long fasting periods deplete the majority of other bacteria outside of Akkermansia, so these fasts should be implemented mindfully with care taken to strategically reintroduce foods to minimize gastric distress and maximize the benefits of the fast.
Research examining the relationship between physical fitness and the microbiome indicate significant differences between the microbial populations present in trained versus sedentary individuals.
In endurance trained individuals, the levels of Akkermansia are higher than sedentary controls. Additionally, middle aged women with an active lifestyle have been shown to possess more Akkermansia than age-matched sedentary women. Both men and women cycling at the professional level had higher levels of Akkermansia than amateur cyclists.
With regards to resistance training, a 6-week program in older adult males was shown to increase rates of mucin synthesis; however, the researchers did not measure Akkermansia abundance, so it’s unclear whether the effects on mucin are attributable to increases in Akkermansia.
Thus, although the relationship between Akkermansia and cardiorespiratory fitness is quite clear, more research needs to be conducted to determine whether resistance exercise also confers benefits to Akkermansia populations specifically.
In the gut, Akkermansia are indispensable for maintaining the integrity of the gut lining and, in doing so, regulating energy homeostasis, blood lipids, glucose control, and systemic inflammation.
Akkermansia consumes polyphenols, like those present in dark fruits and red cabbage, and prebiotics like human milk oligosaccharides. The incorporation of these molecules into one’s daily routine can bolster Akkermansia populations.
Strategic fasting and exercise also exert beneficial effects on Akkermansia populations and improve the health of the gut mucus layer. Intriguingly, recent research indicates that a pasteurized Akkermansia postbiotic shows equal or greater efficacy at improving health markers than a live Akkermansia probiotic. Additional research is prudent to determine whether the efficacy of Akkermansia probiotics and postbiotics is maintained in human subjects.
Jean Looker
March 10, 2023
Thank you very informative & much appreciated