How Akkermansia Survives and Thrives in the Gut?

June 27, 2024 6 min read

How Akkermansia Survives and Thrives in the Gut?

Akkermansia is making a name for itself in the research world. Already hailed as a next-generation probiotic, this prominent gut microbe offers its host protection against obesity, type 2 diabetes, neurological disorders, and infection. 

Yet, a lack of genetic tools has so far made it challenging for scientists to ascertain how A. muciniphila colonises the gut and the impact on its human host's health. Davey and coworkers (2023) described the first genetic clues explaining how Akkermansia grows and colonises the gut. 

Here is the link for the original research article published in Nature Microbiology. 

Davey, Lauren E., et al. "A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression." Nature Microbiology 8.8 (2023): 1450-1467.

Discovering the genes needed to utilise mucin

Akkermansia is a fascinating probiotic. Since its discovery 20 years ago, evidence shows that a low abundance of A. muciniphila is linked with an increased risk of developing multiple diseases[i].

In particular,  A. muciniphila has gained significant traction because of its association with metabolic health. Research has shown that it could offer targeted therapy for obesity[ii] and type 2 diabetes[iii]. However, the understanding of how Akkermansia survives and thrives in the gut has been missing.

Mucin Transported Into Akkermansia Cells

Davey et al., (2023)set about identifying the genes required for Akkermansia to colonise the colon and use mucin for survival. They did this by developing and applying transposon mutagenesis.

Transposon mutagenesisis an important genetic tool that scientists can use to explore the wonderful world of DNA. If you think of DNA like a long list of instructions written into a book, a transposon is an explorer which can move around the different pages. 

The transposon can also insert itself into a sentence to change the structure or meaning. Scientists use the ability of a transposon to randomly insert itself into DNA to discover the purpose of specific DNA sections, particularly how they may relate to health and disease.

Using transposon mutagenesis, Davey and Co found that amino acid biosynthesis is needed for A. muciniphila to grow on mucin. They found that mucin degradation products collect within compartments in bacteria as part of a process that requires genes encoding pili and a plasma protein complex. The researchers called this mucin utilization loci (MUL).

A. muciniphila loves mucin and is the only known gut microbe to use the mucous layer as its chosen energy source[iv]. Because mucins are complex they are usually difficult for microbes to break down. 

So, the scientists watched how A. muciniphila does it by feeding them fluorescently labelled mucin. The mucins were imported and gathered in intracellular areas that the researchers named ‘mucinosomes’.

Overall, it was found that MUL genes were needed for intestinal colonization in mouse models but only when there was competition from other microbes. These genes were discovered to be critical for the transport of mucins and for the development of the mucinosome. 

But it doesn’t stop there.

Mucin degradation by Akkermansia regulates cholesterol metabolism

As part of the transposon mutagenesis process, non-mucin utilising mutants were developed and these could be used to investigate how the host is impacted by Akkermansia’smucin foraging.

The study colonized germ-free mice with wild-type A. muciniphila and MUL mutants and found that A. muciniphila suppressed the activity of colonic genes responsible for cholesterol biosynthesis. 

These are similar to the findings observed by Katiraei et al., (2020). Their study demonstrated that high-cholesterol mice treated daily with oral A. muciniphila for 4 weeks, exhibited lower body weight, and reduced plasma total cholesterol, and triglyceride levels by the end of the intervention[v]

Cholesterol

Cholesterol is a waxy, fatty substance present in your blood. For the most part, cholesterol has a bad name and is associated with poor health outcomes such as coronary heart disease, but the body does need some cholesterol for important functions like making hormones[vi]

However, high levels of ‘bad’ cholesterol or low-density lipoprotein increase the risk of developing atherosclerosis, a condition where cholesterol, fat, and blood cells accumulate on the artery walls, causing them to become narrow. 

These plaques can block the blood flow through the blood vessels, restricting the delivery of oxygen and nutrients to tissues and organs. Restricted blood flow can cause angina or the plaque could form a clot which can travel to other parts of the body, increasing the risk of heart attacks, strokes, and vascular dementia[vii]

How can Akkermansia lower cholesterol?

The study by researchers at Duke University, demonstrated over their 5-year study that when Akkermansia munches on the mucins in the intestinal mucous layer, it can slow down the activity of the genes in the gut responsible for creating cholesterol. 

This further enhances what we already knew, that we (humans) have a symbiotic relationship with our good gut bacteria. By allowing Akkermansia to inhabit the mucosal lining of our gut and munch away on the mucins that make up the mucous, they pay it forward by playing an integral role in managing cholesterol synthesis. 

Future Implications 

Although scientists already have a good idea of the benefits Akkermansia can have for human health, the mechanisms behind how they help are poorly understood. However, Davey and colleagues helped to unravel the molecular link between  Akkermansia’s ability to metabolize mucins and its control over lipid metabolism.

These mechanisms can be used to further understand these interactions and how they can be leveraged further for human health. In the future,  Akkermansia muciniphila could be used as a therapeutic target to treat a wide range of illnesses. For example, the researchers in this study are already looking at how  Akkermansia could be used for vaccine design and exploring its association with neurodegenerative conditions like  amyotrophic lateral sclerosis (ALS), a fierce illness that destroys nerve cells[viii].

How to Increase Akkermansia abundance?

Dietary Polyphenols: Although their preferred choice of sustenance, mucins aren’t the only foods A. muciniphila can utilize to enhance their growth and activity. Dietary polyphenols, like those found in apples, are known to increase the abundance of Akkermansia,as well as other health-promoting species, including Faecalibacterium prausnitzii[ix]

Prebiotic: During early life, Akkermansia can use human milk oligosaccharides for energy. Kostopoulos et al., (2020) demonstrated that A. muciniphila could use human milk to maintain survival during early life[x].

Because Akkermansia can use several host-derived HMOs including 2’-Fucosyllactose (2’-FL), our Akkermansia Daily Probiotic contains 2’-FL to help support the growth of A. muciniphila and other beneficial microbes in your gut. 

Just two capsules of the Akkermansia Daily Probiotic can enhance the integrity of your gut lining, promote a healthy metabolism, and reduce the amount of toxins entering your bloodstream. 

If you’re looking for more in-depth ways to boost your Akkermansia abundance check out our comprehensive guide. It’s packed with information about what’s so special about this microbe and the diet and lifestyle strategies you can adopt to help promote its growth and nurture an optimal environment for it to thrive. 

Summary

The study by Davey and colleagues helps to explain some of the underlying mechanisms that influence the colonization of specific gut microbes and their interaction with their host. In this study, researchers discovered ‘mucinosomes’ and went on further to help unravel the association between  Akkermansia  and cholesterol. These findings are significant and will help to pave a better understanding of how these interactions and benefits can be utilized in the future. 

For now though, if you want to support the  Akkermansia muciniphila colonies in your gut, check out our  AkkermansiaDaily Probiotic.

Written byLeanne 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.  

Sources

[i] Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. Akkermansia muciniphila: Paradigm for next-generation beneficial microorganisms. Nature Reviews Gastroenterology & Hepatology. 2022 May 31;19(10):625–37. doi:10.1038/s41575-022-00631-9

[ii] Cani PD, de Vos WM. Next-generation beneficial microbes: The case of Akkermansia Muciniphila. Frontiers in Microbiology. 2017 Sept 22;8. doi:10.3389/fmicb.2017.01765

[iii] Li J, Yang G, Zhang Q, Liu Z, Jiang X, Xin Y. Function of Akkermansia muciniphila in type 2 diabetes and related diseases. Front Microbiol. 2023 Jun 15;14:1172400. doi: 10.3389/fmicb.2023.1172400. PMID: 37396381; PMCID: PMC10310354.

[iv]  Si J, Kang H, You HJ, Ko G. Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium. Gut Microbes. 2022 Jan-Dec;14(1):2078619. doi: 10.1080/19490976.2022.2078619. PMID: 35613313; PMCID: PMC9135416.

[v] Katiraei S, de Vries MR, Costain AH, Thiem K, Hoving LR, van Diepen JA, Smits HH, Bouter KE, Rensen PCN, Quax PHA, Nieuwdorp M, Netea MG, de Vos WM, Cani PD, Belzer C, van Dijk KW, Berbée JFP, van Harmelen V. Akkermansia muciniphila Exerts Lipid-Lowering and Immunomodulatory Effects without Affecting Neointima Formation in Hyperlipidemic APOE*3-Leiden.CETP Mice. Mol Nutr Food Res. 2020 Aug;64(15):e1900732. doi: 10.1002/mnfr.201900732. Epub 2019 Aug 16. PMID: 31389129; PMCID: PMC7507188.

[vi] About cholesterol [Internet]. Centers for Disease Control and Prevention; 2023 [cited 2024 May 9]. Available from: https://www.cdc.gov/cholesterol/about.htm 

[vii] What is atherosclerosis? [Internet]. U.S. Department of Health and Human Services; [cited 2024 May 9]. Available from: https://www.nhlbi.nih.gov/health/atherosclerosis

[viii] Amyotrophic lateral sclerosis (ALS) [Internet]. U.S. Department of Health and Human Services; [cited 2024 May 9]. Available from: https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als

[ix] Garcia-Mazcorro JF, Pedreschi R, Yuan J, Kawas JR, Chew B, Dowd SE, Noratto G. Apple consumption is associated with a distinctive microbiota, proteomics and metabolomics profile in the gut of Dawley Sprague rats fed a high-fat diet. PLoS One. 2019 Mar 14;14(3):e0212586. doi: 10.1371/journal.pone.0212586. PMID: 30870465; PMCID: PMC6417679.

[x] Kostopoulos I, Elzinga J, Ottman N, Klievink JT, Blijenberg B, Aalvink S, et al. Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro. Scientific Reports. 2020 Aug 31;10(1). doi:10.1038/s41598-020-71113-8


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