Akkermansia muciniphila

Akkermansia muciniphila is a species of human intestinal mucin-degrading bacterium, the type species for a new genus, Akkermansia, proposed in 2004 by Muriel Derrien and others.[1][2]:1474 Extensive research is being undertaken to understand its association with obesity, diabetes, and inflammation.[3][4][5][6][7]

Akkermansia muciniphila
Scientific classification
Kingdom:
Bacteria
Phylum:
Verrucomicrobia
Class:
Verrucomicrobiae
Order:
Verrucomicrobiales
Family:
Akkermansiaceae
Genus:
Akkermansia
Species:
A. muciniphila
Binomial name
Akkermansia muciniphila
Derrien et al 2004

Biology and Biochemistry

A. muciniphila is a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium. Its type strain is MucT (=ATCC BAA-835T =CIP 107961T).[2] A. muciniphila is able to use mucin as its sole source of carbon and nitrogen, is culturable under anaerobic conditions on medium containing gastric mucin, and is able to colonize the gastrointestinal tracts of a number of animal species.[2][8]

Recently, A. muciniphila strain Urmite became the first (evidently) unculturable bacterial strain to be sequenced in its entirety entirely from a human stool sample.[9]

Human metabolism

A. muciniphila is believed to have anti-inflammatory effects in humans, and studies have shown inverse relationships between A. muciniphila colonization and inflammatory conditions such as appendicitis or inflammatory bowel disease (IBD). In one study, reduced levels of A. muciniphila correlated with increased severity of appendicitis. In a separate study, IBD patients were found to have lower levels A. muciniphila in their intestinal tract than individuals without IBD.[8]

Researchers have discovered that A. muciniphila could be used to combat obesity and type 2 diabetes. The study was carried out with mice, overfed to contain three times more fat than their lean cousin. The obese mice were then fed the bacteria, which were shown to reduce the fat burden of the mice by half without any change to the mice's diet. A study published in June 2015 showed an association between A. muciniphila abundance, insulin sensitivity, and healthier metabolic status in overweight/obese adults. The healthier subjects were those with high A. muciniphila abundance and gut microbial richness. In addition, this study showed that having higher abundance of A. muciniphila at baseline was associated with greater clinical benefits after weight loss.[6] The bacterium is naturally present in the human digestive tract at 3-5%, but has been seen to fall with obesity. It is thought that consuming the bacterium increases gut wall thickness, with the addition of mucin, which will block food from being absorbed by the body.[10]

In August 2015, additional research demonstrated that dietary fats influence the growth of Akkermansia muciniphilia relative to other bacterium in the dietary tract. Researchers conducted a study in which mice were fed diets which varied in fat composition but were otherwise identical: one group received lard, while the other received fish oil. After 11 weeks, the group receiving a fish oil diet had increased levels of A. muciniphila and bacterium of genus Lactobacillus, while the group receiving a lard diet had decreased levels of A. muciniphila and Lactobacillus. Additionally, fecal material from mice on the fish oil diet or the lard based diet was transplanted into a new group of mice which had their native gut flora eradicated by antibiotics. All of these mice were then fed a lard based diet. Despite receiving the same lard-based diet for 3 weeks, recipients of transplants from lard-fed donor mice showed increased levels of Lactobacillus and increased levels of inflammation, while recipients of transplants from fish oil-fed donors showed increased levels of A. muciniphila and decreased levels of inflammation. Researchers concluded that the increase in A. muciniphila corresponded to a reduction in inflammation, indicating a link between dietary fats, gut flora composition, and inflammation levels.[5]

Effects in cancer immunotherapy treatment

One study looked at 249 patients with lung or kidney cancer, A. muciniphila was in 69% of patients that did respond compared with just a third of those who did not. Boosting levels of A. muciniphila in mice seemed to also boost their response to immunotherapy.[11]

Effects in ALS in a mouse model

Researchers discovered that a mouse model of Amyotrophic lateral sclerosis suffers from an abnormal gut microbiome, and that supplementing these mice with Akkermansia muciniphila improved their symptoms, slowed the progression of their disease, and increased their survival.[12] Moreover, they found that A. muciniphila produce the vitamin nicotinamide, which when injected into the diseased mice improved their motor symptoms, although it did not increase their lifespan as the bacteria had.[12] They also found lower levels of nicotinamide in the circulation and the cerebrospinal fluid (CSF) of a small sample human ALS patients compared to their family members, and lower levels of A. muciniphila in their stool.[12] In addition, ALS patients with lower levels of nicotinamide in their blood tended to have worse symptoms than patients with higher levels.[12]

References
  1. de Vos, W.M. (2017). "Microbe Profile: Akkermansia muciniphila: a conserved intestinal symbiont that acts as the gatekeeper of our mucosa". Microbiology. 1635 (5): 646–648. doi:10.1099/mic.0.000444. PMID 28530168.
  2. Derrien, M. (2004). "Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium". International Journal of Systematic and Evolutionary Microbiology. 54 (5): 1469–1476. doi:10.1099/ijs.0.02873-0. ISSN 1466-5026. PMID 15388697.
  3. Everard, A.; Belzer, C.; Geurts, L.; Ouwerkerk, J. P.; Druart, C.; Bindels, L. B.; Guiot, Y.; Derrien, M.; Muccioli, G. G.; Delzenne, N. M.; de Vos, W. M.; Cani, P. D. (2013). "Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity". Proceedings of the National Academy of Sciences. 110 (22): 9066–9071. doi:10.1073/pnas.1219451110. ISSN 0027-8424. PMC 3670398. PMID 23671105.
  4. Wageningen University and Research Centre (2013, May 15). Intestinal bacterium Akkermansia curbs obesity. ScienceDaily. Retrieved August
  5. Caesar, Robert; Tremaroli, Valentina; Kovatcheva-Datchary, Petia; Cani, Patrice D.; Bäckhed, Fredrik (2015). "Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling". Cell Metabolism. 22 (4): 658–668. doi:10.1016/j.cmet.2015.07.026. PMC 4598654. PMID 26321659. Mice that received microbiota from a lard-fed donor showed increased adiposity and inflammation, together with a significant increase in Lactobacillus, compared to mice that received microbiota from a fish-oil-fed donor. Therefore, these data do not provide evidence for a role of Lactobacillus in reducing inflammation. However, we found that the enrichment of Akkermansia co-occurred with partial protection against adiposity and inflammation in mice transplanted with fish-oil microbiota and fed a lard diet, highlighting Akkermansia as a potential mediator of the improved inflammatory and metabolic phenotype of mice fed fish oil.
  6. Dao, Maria Carlota; Everard, Amandine; Aron-Wisnewsky, Judith; Sokolovska, Nataliya; Prifti, Edi; Verger, Eric O.; Kayser, Brandon D.; Levenez, Florence; Chilloux, Julien (2015-06-22). "Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology". Gut. 65 (3): 426–436. doi:10.1136/gutjnl-2014-308778. ISSN 1468-3288. PMID 26100928.
  7. Derrien, Muriel; Belzer, Clara; de Vos, Willem M. (2016-02-11). "Akkermansia muciniphila and its role in regulating host functions". Microbial Pathogenesis. 106: 171–181. doi:10.1016/j.micpath.2016.02.005. hdl:10138/236401. ISSN 1096-1208. PMID 26875998.
  8. van Passel MW, Kant R, Zoetendal EG, 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. doi:10.1371/journal.pone.0016876. PMC 3048395. PMID 21390229.
  9. Caputo, Aurélia; Dubourg, Grégory; Croce, Olivier; Gupta, Sushim; Robert, Catherine; Papazian, Laurent; Rolain, Jean-Marc; Raoult, Didier (2015-01-01). "Whole-genome assembly of Akkermansia muciniphila sequenced directly from human stool". Biology Direct. 10: 5. doi:10.1186/s13062-015-0041-1. ISSN 1745-6150. PMC 4333879. PMID 25888298.
  10. Owens, Brian (13 May 2013). "Gut microbe may fight obesity and diabetes". Nature. doi:10.1038/nature.2013.12975. Retrieved 14 May 2013.
  11. http://science.sciencemag.org/content/early/2017/11/01/science.aan3706 Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors
  12. https://www.nature.com/articles/s41586-019-1443-5 Potential roles of gut microbiome and metabolites in modulating ALS in mice

Further reading
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