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Pharmaceuticals
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Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis
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Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (25 February 2025) | Viewed by 11925

Special Issue Editors

Prof. Dr. George Kolios

E-Mail Website
Guest Editor
Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
Interests: gastroenterology; immunopharmacology; mucosal immunology; intestinal inflammation; inflammatory bowel diseases; gut fibrosis; microbiome; stem cell biology
Special Issues, Collections and Topics in MDPI journals
Dr. Eirini Filidou

E-Mail Website
Guest Editor
Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Dragana, 68100 Alexandroupolis, Greece
Interests: mucosal immunology; intestinal inflammation; gut fibrosis; microbiome; stem cell biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

The intestinal microbiota form a dynamic ecosystem, constantly in communication with both the host and the external environment. Among the many benefits to the human organism, such as the development and function of the gastrointestinal tract and the intestinal immune system, microbiota also play a crucial role in defense and nutrient supply. These latter two can be accomplished through either microbial antagonism or microbial metabolic activity. Microbial metabolic activity is implicated in a number of processes, such as fermentation of food carbohydrates, metabolism of xenobiotic substances, production of vitamins, as well as defense against pathogens. Nonetheless, disruption in the composition of the intestinal microbiota leads to a state of dysbiosis, which can also be observed at the metabolic level, and has been associated with various disorders and diseases not only of the digestive tract, such as inflammatory bowel diseases, but also of other organs and systems of the body. It seems that microbial dysbiosis and its disrupted metabolic activity play a pivotal role in the development of intestinal inflammation and fibrosis. Therefore, therapeutic manipulation of dysbiosis and microbial metabolic activity, using probiotics or postbiotics/metabiotics, may have a beneficial effect on various disorders. In addition, microbial metabolites are involved in body physiology through a number of metabolite receptors, expressed in the gut mucosa, and their depletion appears to be involved in the pathophysiology of many diseases. Considering these observations, microbial metabolites and their mucosal receptors may be of interest for the development of new therapeutic strategies or may be important markers for indicating response to therapies. This Special Issue aims to present the latest therapeutic intervention findings on the role of gut microbiota and their metabolites in IBD.

Prof. Dr. George Kolios
Dr. Eirini Filidou
Guest Editors

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Keywords

  • intestinal inflammation
  • inflammatory bowel diseases
  • microbiota
  • microbiome
  • probiotics
  • fecal transplantation

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Published Papers (4 papers)

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14 pages, 2318 KiB  
Article
Impact of Microbiota and Metabolites on Intestinal Integrity and Inflammation in Severe Obesity
by Emma Custers, Debby Vreeken, Frank Schuren, Tim J. van den Broek, Lieke van Dongen, Bram Geenen, Ivo de Blaauw, Maximilian Wiesmann, Eric J. Hazebroek, Robert Kleemann and Amanda J. Kiliaan
Pharmaceuticals 2024, 17(7), 918; https://doi.org/10.3390/ph17070918 - 10 Jul 2024
Viewed by 1273
Abstract
Obesity is a multifactorial disease associated with low-grade inflammation. The gut is thought to be involved in obesity-related inflammation, as it is continuously exposed to antigens from food, microbiota and metabolites. However, the exact underlying mechanisms are still unknown. Therefore, we examined the [...] Read more.
Obesity is a multifactorial disease associated with low-grade inflammation. The gut is thought to be involved in obesity-related inflammation, as it is continuously exposed to antigens from food, microbiota and metabolites. However, the exact underlying mechanisms are still unknown. Therefore, we examined the relation between gut pathology, microbiota, its metabolites and cytokines in adults with severe obesity. Individuals eligible for bariatric surgery were included. Fecal and plasma samples were collected at surgery timepoint, to assess microbiota and metabolite composition. Jejunal biopsies were collected during surgery and stained for cytotoxic T cells, macrophages, mast cells and tight junction component zonula occludens-1. Based on these stainings, the cohort was divided into four groups: high versus low intestinal inflammation and high versus low intestinal integrity. We found no significant differences in microbiota diversity between groups, nor for individual bacterial species. No significant differences in metabolites were observed between the intestinal inflammatory groups. However, some metabolites and cytokines differed between the intestinal integrity groups. Higher plasma levels of interleukin-8 and tauro-chenodeoxycholic acid were found, whereas isovaleric acid and acetic acid were lower in the high intestinal integrity group. As the results were very subtle, we suggest that our cohort shows very early and minor intestinal pathology. Full article
(This article belongs to the Special Issue Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis)
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20 pages, 3918 KiB  
Article
Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis
by Michail Spathakis, Nikolas Dovrolis, Eirini Filidou, Leonidas Kandilogiannakis, Gesthimani Tarapatzi, Vassilis Valatas, Ioannis Drygiannakis, Vasilis Paspaliaris, Konstantinos Arvanitidis, Vangelis G. Manolopoulos, George Kolios and Stergios Vradelis
Pharmaceuticals 2024, 17(4), 492; https://doi.org/10.3390/ph17040492 - 12 Apr 2024
Cited by 2 | Viewed by 1901
Abstract
Metabolites produced by dysbiotic intestinal microbiota can influence disease pathophysiology by participating in ligand–receptor interactions. Our aim was to investigate the differential expression of metabolite receptor (MR) genes between inflammatory bowel disease (IBD), healthy individuals (HIs), and disease controls in order to identify [...] Read more.
Metabolites produced by dysbiotic intestinal microbiota can influence disease pathophysiology by participating in ligand–receptor interactions. Our aim was to investigate the differential expression of metabolite receptor (MR) genes between inflammatory bowel disease (IBD), healthy individuals (HIs), and disease controls in order to identify possible interactions with inflammatory and fibrotic pathways in the intestine. RNA-sequencing datasets containing 643 Crohn’s disease (CD) patients, 467 ulcerative colitis (UC) patients and 295 HIs, and 4 Campylobacter jejuni-infected individuals were retrieved from the Sequence Read Archive, and differential expression was performed using the RaNA-seq online platform. The identified differentially expressed MR genes were used for correlation analysis with up- and downregulated genes in IBD, as well as functional enrichment analysis using a R based pipeline. Overall, 15 MR genes exhibited dysregulated expression in IBD. In inflamed CD, the hydroxycarboxylic acid receptors 2 and 3 (HCAR2, HCAR3) were upregulated and were associated with the recruitment of innate immune cells, while, in the non-inflamed CD ileum, the cannabinoid receptor 1 (CNR1) and the sphingosine-1-phospate receptor 4 (S1PR4) were downregulated and were involved in the regulation of B-cell activation. In inflamed UC, the upregulated receptors HCAR2 and HCAR3 were more closely associated with the process of TH-17 cell differentiation, while the pregnane X receptor (NR1I2) and the transient receptor potential vanilloid 1 (TRPV1) were downregulated and were involved in epithelial barrier maintenance. Our results elucidate the landscape of metabolite receptor expression in IBD, highlighting associations with disease-related functions that could guide the development of new targeted therapies. Full article
(This article belongs to the Special Issue Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis)
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Review

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25 pages, 941 KiB  
Review
Intestinal Fibrogenesis in Inflammatory Bowel Diseases: Exploring the Potential Role of Gut Microbiota Metabolites as Modulators
by Sara Cicchinelli, Stefania Gemma, Giulia Pignataro, Andrea Piccioni, Veronica Ojetti, Antonio Gasbarrini, Francesco Franceschi and Marcello Candelli
Pharmaceuticals 2024, 17(4), 490; https://doi.org/10.3390/ph17040490 - 11 Apr 2024
Cited by 2 | Viewed by 2160
Abstract
Fibrosis, sustained by the transformation of intestinal epithelial cells into fibroblasts (epithelial-to-mesenchymal transition, EMT), has been extensively studied in recent decades, with the molecular basis well-documented in various diseases, including inflammatory bowel diseases (IBDs). However, the factors influencing these pathways remain unclear. In [...] Read more.
Fibrosis, sustained by the transformation of intestinal epithelial cells into fibroblasts (epithelial-to-mesenchymal transition, EMT), has been extensively studied in recent decades, with the molecular basis well-documented in various diseases, including inflammatory bowel diseases (IBDs). However, the factors influencing these pathways remain unclear. In recent years, the role of the gut microbiota in health and disease has garnered significant attention. Evidence suggests that an imbalanced or dysregulated microbiota, along with environmental and genetic factors, may contribute to the development of IBDs. Notably, microbes produce various metabolites that interact with host receptors and associated signaling pathways, influencing physiological and pathological changes. This review aims to present recent evidence highlighting the emerging role of the most studied metabolites as potential modulators of molecular pathways implicated in intestinal fibrosis and EMT in IBDs. These studies provide a deeper understanding of intestinal inflammation and fibrosis, elucidating the molecular basis of the microbiota role in IBDs, paving the way for future treatments. Full article
(This article belongs to the Special Issue Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis)
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18 pages, 784 KiB  
Review
Gut Microbiota Metabolites: Unveiling Their Role in Inflammatory Bowel Diseases and Fibrosis
by Francesca Bernardi, Ferdinando D’Amico, Sarah Bencardino, Ilaria Faggiani, Jacopo Fanizza, Alessandra Zilli, Tommaso Lorenzo Parigi, Mariangela Allocca, Silvio Danese and Federica Furfaro
Pharmaceuticals 2024, 17(3), 347; https://doi.org/10.3390/ph17030347 - 7 Mar 2024
Cited by 6 | Viewed by 5524
Abstract
In recent years, there has been a growing focus on the intricate interplay between the gut microbiota and host health, specifically in the context of inflammatory bowel diseases (IBDs). The gut microbiota produces a diverse array of metabolites, influencing the host’s immune response [...] Read more.
In recent years, there has been a growing focus on the intricate interplay between the gut microbiota and host health, specifically in the context of inflammatory bowel diseases (IBDs). The gut microbiota produces a diverse array of metabolites, influencing the host’s immune response and tissue homeostasis. Noteworthy metabolites, such as short-chain fatty acids, bile acids, and indoles, exert significant effects on intestinal inflammation and fibrosis. This review integrates current research findings to clarify the mechanisms through which gut microbiota metabolites contribute to the progression of IBD and fibrosis, offering insights into potential therapeutic targets and strategies for managing these intricate gastrointestinal conditions. The unraveling of the complex relationship between gut microbiota metabolites and inflammatory processes holds promise for the development of targeted interventions that could lead to more effective and personalized treatment approaches for individuals affected by IBD and subsequent intestinal fibrosis. Full article
(This article belongs to the Special Issue Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis)
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