Akkermansia: a next-generation probiotic

How To Increase Akkermansia

Many of us are now familiar with the terms lactobacillus and bifidobacteria. These are often included in probiotic supplements, and found in fermented foods such as kefir, now widely available in many supermarkets and health food stores. But are you familiar with the bacteria Akkermansia muciniphila (bare with me!)?

What Is Akkermansia muciniphila?

Akkermansia muciniphila has been described as a “next-generation beneficial microbe”. It is one of the most abundant single bacterial species in the human gut, accounting for approximately 3–5% of the total bacteria present there.

Akkermansia muciniphila is inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation.

How Does Akkermansia muciniphila benefit us?

The exact mechanisms by which A. muciniphila exerts its beneficial impact have not been fully established, but it has been suggested that two primary factors are:

  • Its positive impact on the mucosal lining of the gut (specifically mucosal thickness)
  • Improving gut barrier integrity (i.e. improving or preventing leaky gut)

A. muciniphila supplementation was able to restore mucus thickness in obese and type 2 diabetic mice where gut mucus was disrupted by high fat diet treatment; the treatment also resulted in a significant reduction of serum lipopolysaccharides (LPS), a metabolic endotoxemia, and improved the metabolic profile.

What does this quote mean?

LPS is a major component of the outer membrane of gram-negative bacteria and its presence (or excess presence) in circulation often indicates leaky gut, thus a disruption of intestinal mucus.

Intestinal mucus is synthesised and secreted by ‘goblet cells’, and consists of two layers: an inner unstirred layer devoid of bacteria and a thicker outer layer which houses commensal bacteria. The major component of mucus, mucins, are a source of nutrients for A. muciniphila.

Recent studies showed that A. muciniphila, despite its utilisation of mucin as a source of nutrients, is positively associated with the mucus thickness and intestinal barrier integrity in humans and animals.

How A. muciniphila could promote mucus thickness is not known. One of the reasons could be A. muciniphila stimulates mucus turnover rate by making short-chain fatty acids from the degraded mucin. Short chain fatty acids (SCFAs) are the preferable energy source for the the cells that line the gut, which synthesise and secret mucin. Indeed, A. muciniphila supplementation increased the number of mucin-producing goblet cells in mice.

A. muciniphila produces a variety of fermentation products, including SCFA, through mucin degradation. These substrates may serve as energy sources for other bacteria and the host. It is possible that through this cross-feeding,  A. muciniphila may contribute to the expansion of other beneficial species, while it may itself have a direct effect on host metabolism

There is another possible mechanism by which A. muciniphila benefits it’s host.The following quote I found very interesting:

A. muciniphila produces sulfatases and it may be able to use hydrogen sulfide for cysteine production and, as a result, limit the possible toxicity of sulfate-reducing bacteria

Hydrogen sulphide can contribute to gastrointestinal symptoms and there is a lot of discussion at the moment around hydrogen sulphide SIBO (small intestine bacterial overgrowth). This is a pretty important point considering some of my clients have no detectable Akkermansia (as don’t I).

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How Do I Increase Akkermansia?

So with all of this is mind, the natural question becomes how can we support a healthy level of A. muciniphila? Well there are no natural sources of akkermansia, and no akkermansia supplement, it is about providing substrate/food for it to flourish.

  • Grape polyphenols have been shown to dramatically increase the growth of Akkermansia muciniphila (in mice). They also increased intestinal gene expression of ‘proglucagon’, a precursor of proteins that promote insulin production and gut barrier integrity.
  • Cranberry extract
  • Pomegranate extract  1000 mg of POM extract daily for four weeks
  • Quercetin was associated with a trend toward increased Akkermansia in the gut microbiota (in rats)
  • Rhubarb has increased presence of Akkermansia (in mice)
  • Drinking a pomegranate extract (in humans) displayed increased presence of Akkermansia in stool samples. This last report is of particular interest because it not only shows that the human gut microbiota also responds with a major shift in Akkermansia abundance when challenged with high polyphenol intake, as it also suggests that healthy individuals may also take advantage of the prebiotic effects of polyphenols on Akkermansia.
  • A diet rich in omega-3 polyunsaturated fatty acids from fish oil, was recently shown to increase Akkermansia population (in mice).
  • Interestingly, anti-diabetic treatments, such as metformin administration and bariatric surgery were both found to be associated with a marked increase in the abundance of Akkermansia muciniphila.
  • Calorie restriction: The information is very limited about the impact of caloric restriction on gut microbiota and Akkermansia muciniphilaWhile one study (on mice) showed benefit a more recent human study showed an opposite effect – that caloric restriction actually reduced Akkermansia muciniphila abundance on obese or overweight subjects.
  • Previous studies have consistently shown that high-fat diet significantly reduced A. muciniphila abundance in different animal models.
  • A higher FODMAP diet may increase Akkermansia muciniphila
  • Avoid heavy alcohol consumption
  • Although no human study has been reported, three animal studies consistently showed that oral administration of fructo-oligosaccharides (oligofructose or FOS), a common prebiotic, promoted the growth of A. muciniphila
  • There is also evidence to suggest that an increase of short chain fatty acids (SCFAs) may be a promoting effect for Akkermansia muciniphila since SCFAs promote mucin growth, and Akkermansia muciniphila is a mucin-degrading bacterium. We can increase SCFAs via an increase in dietary fibre, and the supplementation of certain probiotics including those containing  bifidobacterium.
  • Three studies showed that a Western high-fat diet in as short as 4 weeks were able to significantly reduce the abundance of A. muciniphila.

FOS may be a preferable nutrient for A. muciniphila.

Frequently Asked Questions

Does Akkermansia Supplements Work?

One randomised, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial.

After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation. However the overall gut microbiome composition was unaffected.

The authors of this study concluded, that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters (source).

How Do I Get Akkermanisa In My Diet?

Unfortunately, there are no foods that contain the bacteria Akkermansia. However, you can eat certain foods that will its growth in the gut. These include foods rich in polyphenols, including apples, beans, berries, grapes, flaxseed, green tea, olives, asparagus, and onions.

What Polyphenols Are Best For Akkermansia?

We need further research as at this point in time the research is contradictory, and, not may have been conduced in humans(!).

However the research states that the best polyphenols may be pomegranate, green tea, and cranberry. (source)

Does Fasting Increase Akkermansia?

There are only two studies available so the information is very limited about the impact of caloric restriction on A. muciniphila.

However, a recent human study showed an opposite effect that caloric restriction actually reduced A. muciniphila abundance in overweight individuals. The study, performed on a small group of only 49 people found that Akkermansia at baseline was inversely related to fasting glucose, waist-to-hip ratio and subcutaneous adipocyte diameter.

However, caloric restriction resulted in a decrease in Akkermansia abundance in the group that had higher Akkermansia levels and no change in the group who had lower than average levels of Akkermansia, though caloric restriction significantly improved insulin sensitivity and other clinical parameters in all groups.

The authors did show that individuals with a higher baseline of Akkermansia had greater improvement in clinical parameters after caloric restriction, suggesting an interaction between caloric restriction and Akkermansia.

My Interview With Kiran Krishnan

It’s early days however…

We do need to be mindful that this research is in it’s infancy.

We cannot conclude whether faecal bacterial abundance is directly proportional to abundance in the gut. Microbiota in the mucus layer differs from that of the intestinal lumen, and Akkermansia muciniphila is closely associated to the gut mucosal layer. The observed differences in abundance of Akkermansia muciniphila into faeces may be due to actual changes in bacterial numbers, or alterations of the mucosal layer and gut architecture.

What this quote is suggesting is we need to be mindful how we interpret stool test results. They may not reflect, as accurately as we would like, the abundance of these organisms in the gut, especially those organisms that are associated with the mucus layer that lines the digestive tract.

We also need to be mindful that more is not always better. High levels of Akkermansia muciniphila (when akkermanisa is too high in stool results for example) may in fact indicate sub-optimal gut health as the above quote touches upon.

And ultimately, based on the above recommendations around increasing Akkermansia muciniphila, we come back to one main recommendation: eat a wide range of colourful plant-based foods.

Can We Test Levels of Akkermansia?

Stool testing can assess levels of A. muciniphila. Click here to order a stool test from Healthpath, where you will also receive a personalised report of your results.

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