Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How?

Geerlings, Sharon Y.; Kostopoulos, Ioannis; Vos, Willem M. de; Belzer, Clara

doi:10.3390/microorganisms6030075

Cited by 321 publications

(284 citation statements)

References 189 publications

(319 reference statements)

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“…Various studies have described positive associations between the abundance of Akkermansia and intestinal health [3, 4]. For example, A. muciniphila affects glucose metabolism, intestinal immunity, and its abundance in the gastrointestinal tract (GIT) is inversely correlated with diseases including Crohn’s disease, ulcerative colitis, and acute appendicitis [32–35]. Although a number of 16S rRNA gene variants have been observed [12] and dozens of isolates have been obtained [14], human-associated Akkermansia have largely been thought of as a single species and the functional potential beyond mucin degradation has gone largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…Through comparative genomic analysis, we identified four phylogroups of human-associated Akkermansia , expanding the known genomic diversity of this lineage. Although all 16S rRNA gene sequenced examined here and elsewhere [32] are >97% identical, using an ANI of 95% across genomes as a species level delineation [36, 37] would suggest that each phylogroup represents a different species of Akkermansia . When we examined gene content, several phylogroup specific genes were identified that are predicted to code for functional differences amongst phylogroups further supporting species delineation.…”

Section: Discussionmentioning

confidence: 99%

“…However, if a bacterium colonized the small intestine and produced an appropriate form of cobalamin then the cofactor is possibly available to the human host. With regards to Akkermansia , we do not yet know the form of cobalamin produced by AmII members but Akkermansia -like organisms have been observed throughout the human gastrointestinal tract, including in the small intestine (reviewed in [32]). Interestingly, phylogenetic analyses consistently group AmII and AmIII isolates [14] with clones and other sequences previously observed in the small intestine [32].…”

Section: Discussionmentioning

confidence: 99%

“…With regards to Akkermansia , we do not yet know the form of cobalamin produced by AmII members but Akkermansia -like organisms have been observed throughout the human gastrointestinal tract, including in the small intestine (reviewed in [32]). Interestingly, phylogenetic analyses consistently group AmII and AmIII isolates [14] with clones and other sequences previously observed in the small intestine [32]. Because our genomic sequence data and isolates were obtained from fecal samples, we could not determine if the different phylogroups colonize different segments of the gastrointestinal tract, but it is intriguing to speculate.…”

Section: Discussionmentioning

confidence: 99%

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Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associatedAkkermansia

Kirmiz

Galindo

Cross

et al. 2019

Preprint

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22Background: Akkermansia muciniphila is a mucin-degrading bacterium found in the gut of most 23 healthy humans and is considered a 'next-generation probiotic.' However, knowledge of the 24 genomic and physiological diversity of human associated Akkermansia is limited, as only one 25 species has been formally described. 26Results: To begin to fill this knowledge gap, we reconstructed 35 high-quality metagenome 27 assembled genomes from children and combined them with 40 other publicly available genomes 28 from adults and mice for comparative genomic analysis. We identified at least four species-level 29 phylogroups (AmI-AmIV) with distinct functional potentials. Most notably, we identified the 30 presence of putative cobalamin (vitamin B12) biosynthesis genes within the AmII (n=26/28) and 31AmIII (n=2/2) phylogroups. To test these predictions, 10 novel strains of Akkermansia were 32 isolated from adults and screened for essential vitamin B12 biosynthesis genes via PCR. Two 33 strains of the AmII phylogroup were positive for the presence of vitamin B12 biosynthesis genes, 34 while all AmI strains, including the type strain A. muciniphila Muc T , were negative. To 35 demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and 36 propionate in the presence and absence of vitamin supplementation in representative strains of 37 the AmI and AmII phylogroups since cobalamin is a cofactor in propionate metabolism. Results 38show that the Akkermansia AmII strain produced acetate and propionate in the absence of 39 supplementation, which is indicative of de novo vitamin B12 biosynthesis. In contrast, acetate 40 and succinate were the main fermentation products for the AmI strains when vitamin B12 was 41 not supplied in the culture medium. 42 Conclusions: We identified Akkermansia strains as potentially important vitamin B12 43 biosynthetic bacteria in the human gut. This novel physiological trait of human associated 44 Akkermansia may impact how these bacteria interact with the human host and other members of 45 the human gut microbiome. 46 47 KEYWORDS: Akkermansia, intestinal bacteria, vitamin B12, human gut microbiome, 48 probiotics 49 50 BACKGROUND 51Akkermansia muciniphila is a mucin degrading, gram-negative intestinal bacterium 52 widely present in the human population, typically at 1 to 4% relative abundance [1, 2]. A number 53 of studies in humans [3-5] and rodents [6][7][8] have found positive associations between its 54 abundance and intestinal health, suggesting that Akkermansia may be a beneficial member of the 55 gut microbiome and could be used as a biomarker of a healthy gut [9][10][11]. However, despite a 56 diversity of phylotypes being reported by previous sequence-based studies, A. muciniphila Muc T 57 (ATCC BAA-835) represents the sole described species of the Verrucomicrobia phylum 58 associated with humans [2, 12, 13]. Therefore, before we can fully assess the health potential of 59 human associated Akkermansia, a comprehensive understanding of the genomic and 60 physiol...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associatedAkkermansia

Kirmiz

Galindo

Cross

et al. 2019

Preprint

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“…A. muciniphila is a mucin degrader most abundantly present in the colon able to colonize the mucus layer of the human intestinal tract and reported to play an important role in maintaining the gut barrier . A. muciniphila is capable of using mucin as a carbon, nitrogen, and energy source, and releasing sulfate in a free form .…”

Section: Introductionmentioning

confidence: 99%

Dietary Protein Sources Differentially Affect the Growth of Akkermansia muciniphila and Maintenance of the Gut Mucus Barrier in Mice

Fan¹,

Zhou²,

Liu³

et al. 2019

Molecular Nutrition Food Res

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Scope The gut microbiota plays an essential role in linking diet to host health. The specific role of different dietary proteins on the gut microbiota and health is less understood. Here, the impact of proteins derived from chicken and soy on the gut microbiota and host gut barrier in C57BL/6 mice is investigated. Methods and results Specific‐pathogen‐free and germ‐free mice are assigned to either a chicken‐ or a soy protein‐based diet for 4 weeks. Compared with a chicken‐protein‐based diet, intake of a soy‐protein‐based diet reduces the abundance of A. muciniphila and the number of goblet cells, lowers the level of Muc2 mRNA, and decreases the thickness of the mucus layer in the colon of specific‐pathogen‐free mice. In germ‐free mice, colonization with A. muciniphila combined with intake of a chicken‐protein‐based diet results in a higher expression of the Muc2 mRNA in colon, and surprisingly, an increased potential for oxidative phosphorylation in A. muciniphila compared with colonized mice fed a soy‐protein‐based diet. Conclusion These findings suggest possible mutually beneficial interactions between the growth and function of A. muciniphila and host mucus barrier in response to intake of a chicken‐protein‐based diet contrasting the intake of a soy‐protein‐based diet.

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Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi‐Omics

Tan

Chong

Lim

et al. 2021

Annals of Neurology

121

106

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Objective Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. Methods Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry. Results Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR‐based metabolome. Microbiome and NMR‐based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N‐oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability–gait disorder scores. Interpretation Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut–brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546–559

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Akkermansia muciniphila in the Human Gastrointestinal Tract: When, Where, and How?

Cited by 321 publications

References 189 publications

Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associatedAkkermansia

Comparative genomics guides elucidation of vitamin B12 biosynthesis in novel human associatedAkkermansia

Dietary Protein Sources Differentially Affect the Growth of Akkermansia muciniphila and Maintenance of the Gut Mucus Barrier in Mice

Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi‐Omics

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