Mucosa and microbiota – the role of intrinsic parameters on intestinal wound healing

Kelm, Matthias; Anger, Friedrich

doi:10.3389/fsurg.2022.905049

Cited by 8 publications

(4 citation statements)

References 61 publications

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“…In the current work we demonstrated that various lactobacilli release large amounts of ligands that can specifically activate FPR2 and possibly mediate their probiotic effects. We found that among the strongest FPR2 activators are lactobacilli that were reported to promote wound healing and prevent inflammation in the gut (Kelm and Anger 2022).…”

Section: Discussionmentioning

confidence: 99%

Probiotic Lactobacilli activate Formyl-Peptide Receptor 2

Dorothee,

Ralf,

Ahmed

et al. 2024

Preprint

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Changes in the composition of the human microbiota can negatively impact human health. Probiotic bacteria like many lactobacilli help prevent or repair dysbiosis but it is largely unclear which molecules of these bacteria mediate the probiotic effects. Given the extensive crosstalk between the immune system and microbiome members, we investigated whether lactobacilli activate the formyl-peptide receptor 2 (FPR2), a pattern recognition receptor that is expressed on the surface of intestinal epithelial cells and known to promote wound healing and immune homeostasis. Probiotic strains of Lacticaseibacillus paracasei, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus were isolated from probiotic compounds and sequenced. Calcium influx experiments in FPR1 or FPR2 overexpressing HL60 cells, and primary human neutrophils, along with pharmacological inhibition of FPR2, revealed that culture filtrates of the isolated lactobacilli strongly activate FPR2, promote killing of the methicillin resistant S. aureus USA300 and induce neutrophil chemotaxis. Pretreatment of culture filtrates with proteinase K reduced FPR2 activity, indicating that the FPR2 ligands are peptides. In silico analysis of the amphipathic properties of the signal peptides of lactic acid bacteria identified selected signal peptides of L. plantarum with the ability to predominantly activate FPR2 in vitro. Thereby, via targeted activation of FPR2, peptides released by some lactobacilli are likely to positively influence the outcome of inflammatory gut diseases and could be used to treat inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Probiotic Lactobacilli activate Formyl-Peptide Receptor 2

Dorothee,

Ralf,

Ahmed

et al. 2024

Preprint

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“…FODMAP foods are assumed to aggravate the gut leakage, however, there are no scientific evidences available. In addition, bacteria such as aerotolerant lactobacilli or wound-associated Akkermansia muciniphila might be critical for wound and anastomotic healing in the gut [82]. Moreover, kinase inhibiting drugs like ruxolitinib were found to alleviate inflammation, apoptosis, and intestinal barrier leakage in UC via STAT3 [83].…”

Section: Current Treatment Strategiesmentioning

confidence: 99%

Microbiota driven macrophage mediators in pathogenesis and treatment of gut leakage: current strategies and future perspectives

Samsudin,

Selvakumar,

Sekar

2024

Preprint

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Macrophages play key roles in tissue homeostasis, defense, disease and repair. Macrophages are highly plastic and exhibit distinct functional phenotypes based on micro-environmental stimuli. Despite several advancements in understanding macrophage biology and their different functional phenotypes in various physiological and pathological conditions, currently available treatment strategies targeting macrophages are limited. Macrophages’ high plasticity and diverse functional roles – including tissue injury and wound healing mechanisms – mark them as potential targets to mine for efficient therapeutics to treat diseases. Despite mounting evidence on association of gut leakage with several extra-intestinal diseases, there is no targeted standard therapy to treat gut leakage. Therefore, there is an urgent need to develop therapeutic strategies to treat this condition. Macrophages are the cells that play the largest role in interacting with the gut microbiota in the intestinal compartment and exert their intended functions in injury and repair mechanisms. In this review, we have summarized the current knowledge on the origins and phenotypes of macrophages. The specific role of macrophages in intestinal barrier function, their role in tissue repair mechanisms and their association with gut microbiota are discussed. In addition, currently available therapies and the putative tissue repair mediators of macrophages for treating microbiota dysbiosis induced gut leakage are also discussed. The overall aim of this review is to convey the intense need to screen for microbiota induced macrophage-released pro-repair mediators, which could lead to the identification of potential candidates that could be developed for treating the leaky gut and associated diseases.

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“…This, together with the fact that the products derived from bacteria can regulate the production and secretion of mucin, thus promoting the loss of the integrity of the epithelial barrier ( Figure 1 ). Lastly, epithelial repair is known to be altered in IBD and this is reflected in the creation of aberrant intestinal anastomosis after a bowel resection, giving rise to the recurrence of the disease in the same place ( Kelm and Anger, 2022 ).…”

Section: A Brief Outline Of the Epithelial Barrier Role In The Pathop...mentioning

confidence: 99%

Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition

Macias-Ceja,

Mendoza-Ballesteros,

Ortega-Albiach

et al. 2023

Front. Cell Dev. Biol.

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In inflammatory bowel disease (IBD), chronic inflammation in the gastrointestinal tract can lead to tissue damage and remodelling, which can ultimately result in fibrosis. Prolonged injury and inflammation can trigger the activation of fibroblasts and extracellular matrix (ECM) components. As fibrosis progresses, the tissue becomes increasingly stiff and less functional, which can lead to complications such as intestinal strictures, obstructive symptoms, and eventually, organ dysfunction. Epithelial cells play a key role in fibrosis, as they secrete cytokines and growth factors that promote fibroblast activation and ECM deposition. Additionally, epithelial cells can undergo a process called epithelial-mesenchymal transition, in which they acquire a more mesenchymal-like phenotype and contribute directly to fibroblast activation and ECM deposition. Overall, the interactions between epithelial cells, immune cells, and fibroblasts play a critical role in the development and progression of fibrosis in IBD. Understanding these complex interactions may provide new targets for therapeutic interventions to prevent or treat fibrosis in IBD. In this review, we have collected and discussed the recent literature highlighting the contribution of epithelial cells to the pathogenesis of the fibrotic complications of IBD, including evidence of EMT, the epigenetic control of the EMT, the potential influence of the intestinal microbiome in EMT, and the possible therapeutic strategies to target EMT. Finally we discuss the pro-fibrotic interactions epithelial-immune cells and epithelial-fibroblasts cells.

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Mucosa and microbiota – the role of intrinsic parameters on intestinal wound healing

Cited by 8 publications

References 61 publications

Probiotic Lactobacilli activate Formyl-Peptide Receptor 2

Probiotic Lactobacilli activate Formyl-Peptide Receptor 2

Microbiota driven macrophage mediators in pathogenesis and treatment of gut leakage: current strategies and future perspectives

Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition

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