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Over the past few decades, studies into the human gut microbiota have excelled. What is becoming more and more clear, is how the biological effects that take place are instigated by prebiotic influencers the gut receives via the diet and their interactions with the gut and its host[i].
One emerging hero hailed as a next-generation probiotic is Akkermansia muciniphila and its potential health benefits breeding excitement. A. muciniphila,through its ability to degrade the mucin glycans in the gut lining, can alter nutrient supply chains. Thus, altering the human body’s reaction to potential chronic and metabolic diseases such as obesity and type 2 diabetes[ii].
In this article, we’ll delve into the many ways the abundance of A. muciniphilacan be modulated through its interaction with the host, other bacteria, and diet.
A. muciniphila, is a member of the Verrucomicrobia phylum, it is a gram-negative bacterium and is now believed to be one of the most abundant single species in early life[iii]. It is anaerobic with the ability to manipulate intestinal mucosa changes by degrading the mucus layer. There are several variants of the Verrucomicrobia phylum present in the earth’s elements and minerals, but A. muciniphila is the only one present in the human gut.
Mounting metagenomic data results have shown how this interaction can directly correlate with protecting capabilities against human chronic and autoimmune diseases. This identifies A. muciniphila as a potential immunomodulatory probiotic with exciting prospects ahead for human health.
One important role of the intestinal mucosal layer is to inhibit the growth of potential pathogens hell-bent on instigating inflammation and disease. The sticky mucus layer traps these potential threats, disabling them, and stopping them from causing harm. If they were left to flourish, they would compete for gut domination[iv].
As A. muciniphiladegrades the protein-filled mucosal layer, it provides the nutrients required for the bacteria to use as its main energy source. This interaction is the beginning of a chain of events that will see these actions strengthen the gut lining, supporting the prevention of issues such as a leaky gut, which can pave the way for several chronic illnesses. A high abundance of Akkermansia also induces anti-inflammatory effects and supports gut homeostasis. It is simple maths, but the more A. muciniphilais in abundance, the better your health is likely to be.
A study conducted by Roopchand et al., (2015) investigated the effects of consuming polyphenols as part of a high-fat diet by obese mice.The results found that the inclusion of polyphenols reduced weight gain, intestinal inflammation, visceral adiposity and improved insulin sensitivity. Consequently, the addition of polyphenols also increased the abundance of A.muciniphilaand decreased the Firmicutesto Bacteroidetes ratio, often implicated in the development of obesity[v].
A mini-review by Rodrigues et al., published in 2022 further demonstrated how the positive relationship between the gut and A. muciniphilacan combat, inflammatory bowel disease (IBD), obesity, and diabetes. The review highlighted that the bacterial products, namely postbiotics, derived from this next-generation probiotic could be a powerful line of defence against disease and may even hold the potential for use in targeting chronic inflammatory and metabolic diseases[vi].
In the human gut, mucin is the most important host-derived substance for A. muciniphila.Unlike other probiotic gut bacteria that rely on prebiotic fibre, Akkermansiais unique because it prefers mucins to other available sugars.
A. muciniphila produces a total of 61 enzymes, that it uses to break down the mucin to create ready and available sources of nitrogen and carbon for energy.[vii]
Interestingly, from early life and before the establishment of a full mucin layer, A. Muciniphila is present within the infant's gut, but at this stage, it is happy degrading and using human milk oligosaccharides (HMOs), the glycan or sugar part of human milk as food for energy.
In an in vitro study by Kostopoulos et al., (2020), the results observed that A. muciniphila could be grown on human milk, and it used glycan degrading enzymes, α-l-fucosidases, β-galactosidases, exo-α-sialidases and β-acetylhexosaminidases, to breakdown the structures of the HMOs, 2’-Fucosyllactose (2’-FL), Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), and lactose.
The results not only showed how in early life the HMOs supported the growth and establishment of A. muciniphila,but that this process also creates a syntropy with other bacterial species, providing them with benefits, too.[viii]
Fun fact: Because A. muciniphilacan utilise several host-derived HMOs for growth in vitro, we’ve included 2’-FL in our new AkkermansiaDaily Probiotic, to ensure you can provide your gut, and its inhabitants, with the best support.
The metabolism of bile is closely linked to the gut microbiota. Primary bile acids are converted into secondary bile acids by specific gut bacteria equipped with bile modification enzymes.
A particular secondary bile acid, deoxycholic acid (DCA) increases the growth of A. muciniphila,as can ursodeoxycholic acid (UDCA) as demonstrated in mice. A study by Wu et al., (2023) demonstrated that A. muciniphila could modulate the composition of the gut microbiome and reshape the construction of bile acids and was associated with lower secondary bile acids in the liver and caecum.
Together with its potential to improve glucose tolerance, strengthen the gut barrier, and reduce dysbiosis, the study highlighted that A. muciniphilacould be beneficial in managing metabolic-associated fatty liver disease[ix].
Being an inhabitant of the gut lining, A. muciniphilainteracts with other species and strains also occupying the mucus layer. However, it also interacts with non-mucin degrading strains such as Faecalibacterium prausnitzii, Eubacterium hallii and Anaerostipes caccae.
Research by Chia et al., (2018) found that the degradation of mucin in the intestinal lining by A. muciniphila supports the growth of the butyrate producer A. caccae and the subsequent production of butyrate[x].
On the other hand, the abundance of A. muciniphilacan be boosted by the presence and activity of other probiotic bacteria. Toscano et al., (2017) demonstrated in their preliminary study that supplementation of two well-known probiotic strains, B. longumand L.rhamnosus increased the abundance of A. muciniphila while at the same time reducing potentially harmful species in the gut[xi].
Another study by Deng et al., (2018) discovered that in the presence of B. fragilis, Akkermansia muciniphilaabundance increased in mice with Clostridium difficileinfection[xii]. Several studies have demonstrated that cross-feeding of short-chain fatty acids (SCFAs) can occur between A. muciniphilaand Bifidobacteria.
Fun fact: You can help support your abundance of Akkermansiain your gut with our PureHMO® Prebiotic Powder. A. muciniphilacan use this HMO for survival and growth, while Bifidobacteriathrives on 2’-FL, so an increase in this probiotic’s activity may also support you’re A. muciniphilacolonies.
Although A. muciniphilauses carbohydrates from the mucin layer of the gut for energy, it can also benefit from dietary carbohydrates, such as xylo-oligosaccharides, fructo-oligosaccharides, arabinoxylan, and inulin.
That’s because these prebiotic fibres can feed other beneficial bacteria that indirectly stimulate the growth and activity of Akkermansia,such as Bifidobacteriaand Lactobacillus.Other research has found that a low carbohydrate, ketogenic diet increases A.muciniphila in mice[xiii].
Furthermore, dietary polyphenols have also been shown to support the growth of Akkermansiain the gut. In animal studies, apple pomace which contains an array of beneficial compounds, increased the abundance of A. muciniphila[xiv].
There is a complex interplay between the diet and A. muciniphila'spresence in the gut. Substances known to modulate the mucosal intestinal lining like capsaicin, found in chillies, flavonoids from apple hops, and green tea can all stimulate its growth. Other foods, like those that contain potent phytochemicals, such as white kidney beans and camu camu may help prevent metabolic diseases like obesity and type 2 diabetes through their ability to increase Akkermansia.
Overall, A.muciniphilais a fundamental member of the human gut microbiome which can utilise a variety of different mechanisms to support its growth and activity. Mucin is the only carbon and nitrogen source for Akkermansia which it can get from the gut mucosal lining. However, there are several mechanisms which can increase mucin production which in turn positively benefits A. muciniphila.Dietary polyphenols and host-derived substances, such as bile acids can also increase the activity of Akkermansia.
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
[i] Hagi T, Belzer C. The interaction of Akkermansia muciniphila with host-derived substances, bacteria and diets. Appl Microbiol Biotechnol. 2021 Jun;105(12):4833-4841. doi: 10.1007/s00253-021-11362-3. Epub 2021 Jun 14. PMID: 34125276; PMCID: PMC8236039.
[ii] Zhou K. Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotics in the gut, evidence from dietary intervention studies. J Funct Foods. 2017 Jun;33:194-201. doi: 10.1016/j.jff.2017.03.045. Epub 2017 Mar 29. PMID: 30416539; PMCID: PMC6223323.
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[vi] Rodrigues VF, Elias-Oliveira J, Pereira ÍS, Pereira JA, Barbosa SC, Machado MSG, Carlos D. Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes. Front Immunol. 2022 Jul 7;13:934695. doi: 10.3389/fimmu.2022.934695. PMID: 35874661; PMCID: PMC9300896.
[vii] Qu S, Zheng Y, Huang Y, Feng Y, Xu K, Zhang W, Wang Y, Nie K, Qin M. Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment. Front Microbiol. 2023 Mar 2;14:1111911. doi: 10.3389/fmicb.2023.1111911. PMID: 36937258; PMCID: PMC10018180.
[viii] Kostopoulos I, Elzinga J, Ottman N, Klievink JT, Blijenberg B, Aalvink S, Boeren S, Mank M, Knol J, de Vos WM, Belzer C. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Sci Rep. 2020 Aug 31;10(1):14330. doi: 10.1038/s41598-020-71113-8. PMID: 32868839; PMCID: PMC7459334.
[ix] Hagi T, Belzer C. The interaction of akkermansia muciniphila with host-derived substances, bacteria and diets. Applied Microbiology and Biotechnology. 2021 Jun;105(12):4833–41. doi:10.1007/s00253-021-11362-3
[x] Chia, L. W., Hornung, B. V. H., Aalvink, S., Schaap, P. J., de Vos, W. M., Knol, J., & Belzer, C. (2018). Deciphering the trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach. Antonie van Leeuwenhoek, 111(6), 859–873. https://doi.org/10.1007/s10482-018-1040-x
[xi] Toscano M, De Grandi R, Stronati L, De Vecchi E, Drago L. Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: A preliminary study. World J Gastroenterol. 2017 Apr 21;23(15):2696-2704. doi: 10.3748/wjg.v23.i15.2696. PMID: 28487606; PMCID: PMC5403748.
[xii] Deng H, Yang S, Zhang Y, Qian K, Zhang Z, Liu Y, Wang Y, Bai Y, Fan H, Zhao X, Zhi F. Bacteroides fragilis Prevents Clostridium difficile Infection in a Mouse Model by Restoring Gut Barrier and Microbiome Regulation. Front Microbiol. 2018 Dec 21;9:2976. doi: 10.3389/fmicb.2018.02976. Erratum in: Front Microbiol. 2019 Apr 02;10:601. PMID: 30619112; PMCID: PMC6308121.
[xiii] Ma D, Wang AC, Parikh I, Green SJ, Hoffman JD, Chlipala G, Murphy MP, Sokola BS, Bauer B, Hartz AMS, Lin AL. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Sci Rep. 2018 Apr 27;8(1):6670. doi: 10.1038/s41598-018-25190-5. PMID: 29703936; PMCID: PMC5923270.
[xiv] 1. Dufourny S, Lebrun S, Douny C, Dubois B, Scippo M-L, Wavreille J, et al. Apple pomace modulates the microbiota and increases the propionate ratio in an in vitro piglet gastrointestinal model. Fermentation. 2022 Aug 19;8(8):408. doi:10.3390/fermentation8080408
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