Clade-specific extracellular vesicles from Akkermansia muciniphila mediate competitive colonization via direct inhibition and immune stimulation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 19, 2025

Akkermansia muciniphila, a promising candidate for next-generation probiotics, exhibits significant genomic diversity, classified into several distinct clades (AmI to AmIV). Notably, single clade tends predominate within individual hosts, with co-occurrence of different being rare. The mechanisms driving such clade-specific exclusion remain unclear. Here, we show that extracellular vesicles (EVs) derived from AmII inhibit the growth I (AmI), conferring competitive advantage AmII. Moreover, observe immunoglobulin A (IgA) responses, where IgAs, induced by EVs AmII, facilitate niche occupancy and AmI. These findings provide insights dynamics A. muciniphila suggest future personalized microbiome interventions could be optimized considering composition in hosts.

Language: Английский

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Utilization Efficiency of Human Milk Oligosaccharides by Human-Associated Akkermansia Is Strain Dependent

Applied and Environmental Microbiology, Journal Year: 2021, Volume and Issue: 88(1)

Published: Oct. 20, 2021

Akkermansia muciniphila is a mucin-degrading bacterium found in the human gut and often associated with positive health. However, despite being detected by as early 1 month of age, little known about role infant gut. Human milk oligosaccharides (HMOs) are abundant components structurally similar to that comprise mucin, preferred growth substrate human-associated Akkermansia. A limited subset intestinal bacteria has been shown grow well on HMOs mucin. We therefore examined ability genomically diverse strains HMOs. First, we screened 85 genomes representing four phylogroups examine their metabolic potential degrade Furthermore, representative isolates individual mucin background analyzed resulting metabolites. All were equipped an array glycoside hydrolases HMO deconstruction. Representative all able various efficiencies yields. Strain CSUN-19, belonging AmIV phylogroup, grew highest level presence fucosylated sialylated This activity may be partially related increased copy numbers and/or enzyme activities α-fucosidases, α-sialidases, β-galactosidases. study examines utilization purified phylogroups. Further studies required how ingestion influences microbial ecology infants harboring different IMPORTANCE third most component breast provide several benefits developing infants, including recruitment beneficial largely considered have colostrum, milk, young infants. A. MucT, AmI contributes deconstruction capacity infant. Here, using phylogenomics, genomic capacities deconstruct Indeed, each phylogroup contained differences HMOs, These Akkermansia-HMO interactions potentially influence life, critical time for development microbiome

Language: Английский

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Akkermansia muciniphila Ameliorates Clostridioides difficile Infection in Mice by Modulating the Intestinal Microbiome and Metabolites

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: May 18, 2022

Clostridioides difficile is a common cause of nosocomial infection. Antibiotic-induced dysbiosis in the intestinal microbiota core C. infection (CDI). Akkermansia muciniphila plays an active role maintaining gastrointestinal balance and might offer protective effects on CDI as probiotics. Here, we investigated mechanisms A. CDI. C57BL/6 mice (n = 29) were administered Muc T (3 × 109 CFUs, 0.2 mL) or phosphate-buffered saline (PBS) by oral gavage for 2 weeks. Mice pretreated with antibiotic cocktail subsequently challenged strain VPI 10463. treatment prevented weight loss reduced histological injury colon. And it also alleviated inflammation improved barrier function intestine. The administration may be associated increase short-chain fatty acid production maintenance bile acids' steady-state. Our results provide evidence that to mice, imbalance microbial community structure, lead decrease abundance members Enterobacteriaceae Enterococcaceae. In short, shows potential anti-CDI modulating gut metabolome.

Language: Английский

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Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(671)

Published: Nov. 16, 2022

Not all patients with cancer and severe neutropenia develop fever, the fecal microbiome may play a role. In single-center study of undergoing hematopoietic cell transplant ( n = 119), was characterized at onset neutropenia. A total 63 (53%) developed subsequent their displayed increased relative abundances Akkermansia muciniphila , species mucin-degrading bacteria P 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation melphalan, similarly expanded A. additionally thinned colonic mucus layer in mice. Caloric restriction unirradiated mice also layer. Antibiotic treatment to eradicate before caloric preserved mucus, whereas reintroduction restored thinning. raised luminal pH reduced acetate, propionate, butyrate. Culturing vitro propionate utilization mucin as well fucose. Treating irradiated an antibiotic targeting or layer, suppressed translocation flagellin, inflammatory cytokines colon, improved thermoregulation. These results suggest diet, metabolites, link neutropenic fever guide future microbiome-based preventive strategies.

Language: Английский

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Akkermansia muciniphila: A potential target and pending issues for oncotherapy

Pharmacological Research, Journal Year: 2023, Volume and Issue: 196, P. 106916 - 106916

Published: Sept. 9, 2023

In the wake of development metagenomic, metabolomic, and metatranscriptomic approaches, intricate interactions between host various microbes are now being progressively understood. Numerous studies have demonstrated evident changes in gut microbiota during process a variety diseases, such as diabetes, obesity, aging, cancers. Notably, is viewed potential source novel therapeutics. Currently, Next-generation probiotics (NGPs) gaining popularity therapeutic agents that alter affect cancer development. Akkermansia muciniphila (A. muciniphila), representative commensal bacterium, has received substantial attention over past decade promising NGP. The components metabolites A. can directly or indirectly tumorigenesis, particular through its effects on antitumor immunosurveillance, including stimulation pattern recognition receptors (PRRs), which also leads to better outcomes situations, prevention curation this article, we systematically summarize role tumorigenesis (involving gastrointestinal non-gastrointestinal cancers) tumor therapy. particular, carefully discuss some critical scientific issues need be solved for future using beneficial bacterium treatment, might provide bright clues assistance application drugs targeting clinical oncotherapy.

Language: Английский

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