Gut Microbiota Metabolites in Intestinal Inflammation and Fibrosis

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

Type: Review 

Title: Epithelial to mesenchymal transition in the gut: microbiota metabolites as possible triggers 

Author(s): Sara Cicchinelli¹, Marcello Candelli² et al 

The Corresponding author(s): Marcello Candelli 

Affiliation(s): ¹S.S. Filippo e Nicola Hospital, 67051 Avezzano, L’Aquila, Italy; ²Fondazione Universitaria Policlinico Agostino Gemelli - IRRCS – Roma 

Abstract: The transformation of intestinal epithelial cells to fibroblasts, in the so called epithelial to mesenchymal transition (EMT), has been widely studied in the past decades, and the molecular basis of the phenomenon are well described. Among the molecular pathways leading to EMT, the TGFβ/Smad signalling is one of the better characterized in inflammatory bowel disease (IBD). Anyway, the factors triggering the pathway remain still unclear. In the last years, the role of gut microbiota in heath and disease is gaining great attention. There is evidence that unbalanced or deregulated microbiota, together with environmental and genetic factor, might promote the development IBDs. In fact, it has been reported that microbes release many molecular associated molecular pathways (MAMPs), including various metabolites, that interact with several host receptors, and their associated signalling pathways responsible of many physiologic and pathologic changes. Recent studies have suggested that these microbiota metabolites might act as triggers for the TGFβ/Smad signalling, and related regulatory pathway. These studies give a better insight of the knowledge on intestinal inflammation and fibrosis, elucidating the possible molecular basis of the role of microbiota in IBDs, giving better understanding of the mechanisms subtending the effectiveness of some therapies, and opening perspective for future treatments. 

Expected Submission Time: 29 February 2024 

 Type: Review

• Tentative Title: Gut Microbiota Metabolites: Unveiling their Role in inflammatory bowel diseases and Fibrosis.
• All Author(s) name: Sarah Bencardino¹, Ferdinando D’Amico^{1, 2}, Alessandra Zilli¹, Tommaso Lorenzo Parigi¹, Mariangela Allocca¹, Silvio Danese¹, Federica Furfaro¹
• The Corresponding author(s): Ferdinando D’amico
• All Affiliation(s): 1Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and Vita-Salute San Raffaele University, Milan, Italy; 2 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.
• Tentative Abstract: In recent years, the intricate interplay between gut microbiota and host health has gained substantial attention, particularly in the context of inflammatory bowel diseases (IBD) and fibrosis. This abstract explores the emerging understanding of the role played by gut microbiota metabolites in the pathogenesis of these disorders. The gut microbiota's dynamic metabolic activity generates a diverse array of metabolites, influencing the host's immune response and tissue homeostasis. Key metabolites, such as short-chain fatty acids, bile acids, and indoles, exhibit significant impacts on intestinal inflammation and fibrosis. This review synthesizes current research findings to elucidate the mechanisms through which gut microbiota metabolites contribute to the progression of IBD and fibrosis, shedding light on potential therapeutic targets and strategies for managing these complex gastrointestinal conditions. The unraveling of the intricate relationship between gut microbiota metabolites and inflammatory processes holds promise for the development of targeted interventions that could pave the way for more effective and personalized treatment approaches for individuals affected by IBD and fibrosis.
• Expected Submission Time: March 2024