Role of microbial secreted proteins in gut microbiota-host interactions

Vidal-Veuthey, Boris; González, Dámariz; Cárdenas, Juan Pablo

doi:10.3389/fcimb.2022.964710

Cited by 7 publications

(5 citation statements)

References 88 publications

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“…The gut microbiota is restricted from directly interacting with the intestinal epithelium because it is covered by a mucus layer enriched with immune effectors and antimicrobial peptides targeting the microbiota, thus providing a physical and biochemical barrier 44 , 45 . Therefore, research invested in the mode of action of gut microbiota on host health has acquired more interest in microbiota-secreted factors such as protein, metabolites, and EV that have the potential to penetrate the intestinal mucus layer and reach host cells, as they are interesting candidates for mediating host-microbiome crosstalk 4 . Recently, P9 was identified in the cell-free supernatant of A. muciniphila culture as a new promising probiotic effector that promotes the ability of the bacterium to improve metabolic syndrome in mice with diet-induced obesity by inducing the secretion of glucagon-like peptide-1 11 .…”

Section: Discussionmentioning

confidence: 99%

“…Communication between the host and gut microbiota is mediated by microbiota-derived bioactive molecules, such as surface proteins, secreted proteins, metabolites, and extracellular vesicles (EV) 3 . In particular, extracellular secreted proteins play key mediators in host-microbiome crosstalk, directly interacting with host cells by passing through the mucin layer, thereby modulating host signaling to ensure homeostatic balance 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

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The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

Kang,

Kim,

Kim

et al. 2024

Nat Commun

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Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

Kang,

Kim,

Kim

et al. 2024

Nat Commun

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“…Similarly, in obesity, the altered microbiota can instigate the gut leakiness by reducing tight junctions (Mishra et al., 2023) and facilitating relatively easy access of bacterial biomolecules, including EVs, across the intestine. Bacterial secretions could directly affect host physiology and health (Vidal‐Veuthey et al., 2022) but without the protecting membrane(s), as in bEV, these biomolecules will probably have a shorter half‐life and are prone to be targeted and cleared by the host immune system. Therefore, bEV could play a critical role in gut microbiota and host interaction as well as inform about the dynamic changes in the gut microbiome.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of LPS+ bacterial extracellular vesicles along the gut‐hepatic portal vein‐liver axis

Jain,

Kumar,

Almousa

et al. 2024

J of Extracellular Vesicle

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Gut microbiome dysbiosis is a major contributing factor to several pathological conditions. However, the mechanistic understanding of the communication between gut microbiota and extra‐intestinal organs remains largely elusive. Extracellular vesicles (EVs), secreted by almost every form of life, including bacteria, could play a critical role in this inter‐kingdom crosstalk and are the focus of present study. Here, we present a novel approach for isolating lipopolysaccharide (LPS)+ bacterial extracellular vesicles (bEVLPS) from complex biological samples, including faeces, plasma and the liver from lean and diet‐induced obese (DIO) mice. bEVLPS were extensively characterised using nanoparticle tracking analyses, immunogold labelling coupled with transmission electron microscopy, flow cytometry, super‐resolution microscopy and 16S sequencing. In liver tissues, the protein expressions of TLR4 and a few macrophage‐specific biomarkers were assessed by immunohistochemistry, and the gene expressions of inflammation‐related cytokines and their receptors (n = 89 genes) were measured using a PCR array. Faecal samples from DIO mice revealed a remarkably lower concentration of total EVs but a significantly higher percentage of LPS+ EVs. Interestingly, DIO faecal bEVLPS showed a higher abundance of Proteobacteria by 16S sequencing. Importantly, in DIO mice, a higher number of total EVs and bEVLPS consistently entered the hepatic portal vein and subsequently reached the liver, associated with increased expression of TLR4, macrophage markers (F4/80, CD86 and CD206), cytokines and receptors (Il1rn, Ccr1, Cxcl10, Il2rg and Ccr2). Furthermore, a portion of bEVLPS escaped liver and entered the peripheral circulation. In conclusion, bEV could be the key mediator orchestrating various well‐established biological effects induced by gut bacteria on distant organs.

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“…In Bacteria, ANKRs were mostly investigated in proteobacterial organisms, especially pathogens, where those proteins could be associated with protein secretion systems involved in pathogenic interactions with the host (Al-Khodor et al, 2010). In the case of Akkermansia, those proteins could be part of a set of secreted proteins that could generate an effect on the host, as seen with other secreted and exposed proteins detected in A. muciniphila (Vidal-Veuthey et al, 2022). LAkkCA also encoded a predicted set of genes for Type IV pilus assembly, suggesting a role of this ubiquitous complex, involved in several functions such as motility, biofilm formation, and adherence (Ligthart et al, 2020), in the early adaptation of this genus to the gut environment.…”

Section: Predicted Metabolism and Genetic Features Of Lakkcamentioning

confidence: 98%

Insights into early evolutionary adaptations of the Akkermansia genus to the vertebrate gut

González,

Morales-Olavarria,

Vidal-Veuthey

et al. 2023

Front. Microbiol.

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Akkermansia, a relevant mucin degrader from the vertebrate gut microbiota, is a member of the deeply branched Verrucomicrobiota, as well as the only known member of this phylum to be described as inhabitants of the gut. Only a few Akkermansia species have been officially described so far, although there is genomic evidence addressing the existence of more species-level variants for this genus. This niche specialization makes Akkermansia an interesting model for studying the evolution of microorganisms to their adaptation to the gastrointestinal tract environment, including which kind of functions were gained when the Akkermansia genus originated or how the evolutionary pressure functions over those genes. In order to gain more insight into Akkermansia adaptations to the gastrointestinal tract niche, we performed a phylogenomic analysis of 367 high-quality Akkermansia isolates and metagenome-assembled genomes, in addition to other members of Verrucomicrobiota. This work was focused on three aspects: the definition of Akkermansia genomic species clusters and the calculation and functional characterization of the pangenome for the most represented species; the evolutionary relationship between Akkermansia and their closest relatives from Verrucomicrobiota, defining the gene families which were gained or lost during the emergence of the last Akkermansia common ancestor (LAkkCA) and; the evaluation of the evolutionary pressure metrics for each relevant gene family of main Akkermansia species. This analysis found 25 Akkermansia genomic species clusters distributed in two main clades, divergent from their non-Akkermansia relatives. Pangenome analyses suggest that Akkermansia species have open pangenomes, and the gene gain/loss model indicates that genes associated with mucin degradation (both glycoside hydrolases and peptidases), (micro)aerobic metabolism, surface interaction, and adhesion were part of LAkkCA. Specifically, mucin degradation is a very ancestral innovation involved in the origin of Akkermansia. Horizontal gene transfer detection suggests that Akkermansia could receive genes mostly from unknown sources or from other Gram-negative gut bacteria. Evolutionary metrics suggest that Akkemansia species evolved differently, and even some conserved genes suffered different evolutionary pressures among clades. These results suggest a complex evolutionary landscape of the genus and indicate that mucin degradation could be an essential feature in Akkermansia evolution as a symbiotic species.

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Role of microbial secreted proteins in gut microbiota-host interactions

Cited by 7 publications

References 88 publications

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation

Characterisation of LPS+ bacterial extracellular vesicles along the gut‐hepatic portal vein‐liver axis

Insights into early evolutionary adaptations of the Akkermansia genus to the vertebrate gut

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