Akkermansia muciniphila

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Classification

Domain: Bacteria

Phylum: Verrucomicrobia

Class: Verrucomicrobiae

Order: Verrucomicrobiales

Family: Akkermansiaceae

Species

Akkermansia muciniphila

Description and Significance

Image of Figure 1. Akkermansia muciniphila [7]

Akkermansia muciniphila is an anaerobic, Gram-negative, non-motile, non-spore-forming, oval-shaped bacterium, as seen in Figure 1 [7]. It is present in the human intestinal tract in high quantities, ranging from 39% to 84% of the total bacterial population. A.muciniphila is associated with the protective mucus lining of the intestines. Its presence in the mucus layer of the intestinal tract is particularly important because A.muciniphila is able to degrade host mucin into short chain fatty acids, or other products, to regulate the biological functions of the host [2]. The high content of Akkermansia muciniphila is thought to play a major role in the health of the intestinal mucus, as well as regulate host immune responses and lipid metabolism [5]. Several studies have observed that a decrease of Akkermansia muciniphila in the mucus is correlated with higher rates of obesity, increased inflammation, and an increase in Type 2 diabetes symptoms [1,3,11].

Genome Structure

The complete genome of Akkermansia muciniphila has one circular chromosome of 2,664,102 bp with a G+C content of 55.8%.Akkermansia muciniphila has a total of 2,176 protein coding sequences and an overall coding capacity of 88.8% [7]. Once sequenced, the genome was found to contain many candidate mucinase-encoding genes, but did not seem to have any genes for encoding canonical mucus-binding domains [4,8]. Akkermansia muciniphila's genome did contain numerous phage-associated sequences, which indicates that viruses may have played a role in the evolution of the species.

Cell Structure, Metabolism and Life Cycle

Akkermansia muciniphila is able to use mucin as its sole source of carbon, nitrogen, and energy. It is an obligate chemo-organotroph, as evidenced by a study that found no growth on a basal medium supplemented with vitamins and purged with H2/CO2. After previous research hypothesized that A. muciniphila survived solely on the mucin in the host intestine, it was found that only a mucin medium was needed to culture A. muciniphila. Akkermansia muciniphila was found to produce acetate, propionate, and ethanol from mucin fermentation [7].

Image of Figure 2. Akkermansia muciniphila Function [6]

Ecology and Pathogenesis

Image of Figure 3.Akkermansia muciniphila and obesity [1]

Akkermansia muciniphila colonizes the mucosa layer of the host's gut, where it uses mucin as its sole source of carbon and nitrogen [6]. Though many mucin degrading microbes in the intestinal layer of a host can be pathogenic, A. muciniphila has mostly positive associations with its host. Since A. muciniphila remains in the outer mucosal layer and does not penetrate through to the inner layer, colonization is beneficial because the bacteria promotes the natural turnover of the outer mucin layer [10].

Several studies have found that Akkermansia muciniphila is linked to metabolic homeostasis and its presence in the intestine can help alleviate fat gain and type 2 diabetes as seen in experiments on mice and testing of human feces samples for A. muciniphila. Since A. muciniphila is located close to the animal host epithelial cells, it can stimulate significant regulatory responses. One study found that after exposure to A. muciniphila, the mice epithelial cell line activated TLR-2 expression and tight junction proteins, while reducing pro-inflammatory cytokines in the colon, as seen in Figure 3 [1]. This led to an increase in intestinal barrier integrity, and a decrease in inflammation which led to a decrease in obesity and type 2 diabetes symptoms.

Akkermansia muciniphila can also positively impact host response to cancer immunotherapy. A study found that consumption of antibiotics was associated with poorer response to immunotherapeutic PD-1 blockade. Fecal samples of cancer patients were tested to determine the levels of A. muciniphila present after antibiotic consumption and found that it was much lower in patients that had recently taken antibiotics, and that those patients also had a poorer response to the immunotherapy. To determine that lower levels of Akkermansia muciniphila did have a direct impact on response rate, oral supplements of the bacteria were given to antibiotic-treated mice and found that it restored their response to the immunotherapy. Based on this research, it is suggested that maintaining a healthy gut flora, including mainly Akkermansia muciniphila is important to increase the effectiveness of cancer immunotherapy [9].

References

[1] Ashrafian F, Shahriary A, Behrouzi A, Moradi HR, Keshavarz Azizi Raftar S, Lari A, Hadifar S, Yaghoubfar R, Ahmadi Badi S, Khatami S, Vaziri F and Siadat SD (2019) Akkermansia muciniphila-Derived Extracellular Vesicles as a Mucosal Delivery Vector for Amelioration of Obesity in Mice. Front. Microbiol. 10:2155. doi: 10.3389/fmicb.2019.02155

[2] Bian, Xiaoyuan et al. “Administration of Akkermansia muciniphila Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.” Frontiers in microbiology vol. 10 2259. 1 Oct. 2019, doi:10.3389/fmicb.2019.02259

[3] Cani PD, de Vos WM. Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila. Front Microbiol. 2017;8:1765. Published 2017 Sep 22. doi:10.3389/fmicb.2017.01765

[4] Caputo, Aurélia et al. “Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool.” Biology direct vol. 10 5. 19 Feb. 2015, doi:10.1186/s13062-015-0041-1

[5] Derrien M., Van Baarlen P., Hooiveld G., Norin E., Muller M., De Vos W. M. (2011). Modulation of mucosal immune response, tolerance, and proliferation in mice colonized by the mucin-degrader Akkermansia muciniphila. Front. Microbiol. 2:166. 10.3389/fmicb.2011.00166

[6] Derrien, Muriel, et al. “Akkermansia Muciniphila and Its Role in Regulating Host Functions.” Microbial Pathogenesis, vol. 106, 2017, pp. 171–181., doi:10.1016/j.micpath.2016.02.005.

[7] Derrien, Muriel, et al. “Akkermansia Muciniphila Gen. Nov., Sp. Nov., a Human Intestinal Mucin-Degrading Bacterium.” International Journal Of Systematic And Evolutionary Microbiology, vol. 54, no. 5, Jan. 2004, pp. 1469–1476., doi:10.1099/ijs.0.02873-0.

[8] Guo, Xianfeng et al. “Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas.” BMC genomics vol. 18,1 800. 18 Oct. 2017, doi:10.1186/s12864-017-4195-3

[9] Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018;359:91–7.

[10] van Passel MWJ, Kant R, Zoetendal EG, Plugge CM, Derrien M, Malfatti SA, et al. (2011) The Genome of Akkermansia muciniphila, a Dedicated Intestinal Mucin Degrader, and Its Use in Exploring Intestinal Metagenomes. PLoS ONE 6(3): e16876. https://doi.org/10.1371/journal.pone.0016876

[11] Xu Y, Wang N, Tan HY, Li S, Zhang C, Feng Y. Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems. Front Microbiol. 2020;11:219. Published 2020 Feb 21. doi:10.3389/fmicb.2020.00219

Author

Page authored by Emma Schuster, student of Prof. Jay Lennon at IndianaUniversity.