Akkermansia muciniphila: a “next-generation beneficial microbe”

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 (3–5% of the total bacteria).

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 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 multi-laminated 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).

How do we increase Akkermansia muciniphila?

All three studies showed that Western high-fat diet in as short as 4 weeks were able to significantly reduce the abundance of A. muciniphila

So with all of this is mind, the natural question becomes how can we support a healthy level of A. muciniphila? 

  • 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.19 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, antidiabetic treatments, such as metformin administration and bariatric surgery were both found to be associated with a marked increase in the abundance of A. muciniphila
  • Calorie restriction: The information is very limited about the impact of caloric restriction on gut microbiota and A. muciniphila. While one study (on mice) showed benefit a more recent human study showed an opposite effect – that caloric restriction actually reduced A. 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 A. 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 A. muciniphila since SCFAs promote mucin growth, and A. 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.

FOS may be a preferable nutrient for A. muciniphila.

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 A. muciniphila is closely associated to the gut mucosal layer. The observed differences in abundance of A. 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.

And ultimately, based on the above recommendations around increasing A. 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 Akkermansia. Click here to order a stool test from Healthpath, where you will also receive a personalised report of your results.

References

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223323/
  • https://gut.bmj.com/content/65/3/426
  • https://gut.bmj.com/content/64/1/93?ijkey=5e8cd0fc9677605955952398c280966beb384d6a&keytype2=tf_ipsecsha
  • https://www.ncbi.nlm.nih.gov/pubmed/30420171
  • https://www.ncbi.nlm.nih.gov/pubmed/28798745
  • https://www.ncbi.nlm.nih.gov/pubmed/30416539
  • https://www.ncbi.nlm.nih.gov/pubmed/29107524
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