Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 15886

Special Issue Editors


E-Mail Website
Guest Editor
Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy
Interests: inflammatory bowel disease; intestinal inflammation; colorectal cancer; intestinal epithelial barrier; microbiota; inflammasome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Several studies have shown that gut dysbiosis—characterized by a reduction in microbial diversity, decreased frequency of beneficial bacterial strains and overgrowth of pathobionts—frequently associates with the development of intestinal and extra-intestinal disorders (e.g., neurological disorders). Many environmental factors (including diet, drugs and stress) can trigger gut dysbiosis by altering the complex interaction between microbial ecology and the host immune system, thereby promoting intestinal epithelial barrier dysfunctions that may ultimately lead to the development of several pathological conditions. Targeting gut dysbiosis, in combination with standard therapies, is now considered a valuable and promising strategy to prevent and/or treat gut-related diseases, and a better understanding of the molecular and cellular pathways underlying this condition is definitely required.

In this Special Issue, we invite researchers working on gut dysbiosis to submit original articles or reviews to improve our knowledge on this complex and fascinating field.

Potential topics include, but are not limited to, the following:

  • Role of dysbiotic microbiota and microbial metabolites in gut homeostasis, intestinal barrier function and host immune system;
  • Contribution of gut dysbiosis to the development of intestinal (e.g., inflammatory bowel diseases, colorectal cancer) and extra-intestinal disorders (e.g., neurological disorders, diabetes);
  • Therapeutic strategies for gut microbiota modulation in pathological conditions (e.g., probiotic treatment, fecal microbiota transplantation).

Dr. Federica Laudisi
Dr. Carmine Stolfi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Related Special Issue

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

9 pages, 918 KiB  
Article
Autologous Faecal Microbiota Transplantation to Improve Outcomes of Haematopoietic Stem Cell Transplantation: Results of a Single-Centre Feasibility Study
by Anna Li, Joanne M. Bowen, Imogen A. Ball, Sophie Wilson, Angelina Yong, David T. Yeung, Cindy H. Lee, Robert V. Bryant, Samuel P. Costello, Feargal J. Ryan and Hannah R. Wardill
Biomedicines 2023, 11(12), 3274; https://doi.org/10.3390/biomedicines11123274 - 11 Dec 2023
Viewed by 1393
Abstract
Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we [...] Read more.
Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual’s own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. The stool was collected prior to starting first line therapy. Patients who progressed to HSCT were offered FMT via 3 × retention enemas before day +5 (HSCT = day 0). The feasibility was determined by the recruitment rate, number and volume of enemas administered, and the retention time. Longitudinally collected stool samples were also collected to explore the influence of auto-FMT using 16S rRNA gene sequencing. n = 4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25 (1–3) enemas 43.67 (25–50) mL total, retained for an average of 60.78 (10–145) min. No adverse events (AEs) attributed to the FMT were identified. Although the minimum requirements were met for the volume and retention of auto-FMT, the recruitment was significantly impacted by the logistical challenges of the pretherapy stool collection. This ultimately undermined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)
Show Figures

Figure 1

16 pages, 3497 KiB  
Article
Identifying Microbiome Dynamics in Pediatric IBD: More than a Family Matter
by Nikolas Dovrolis, Anastasia Moschoviti, Smaragdi Fessatou, George Karamanolis, George Kolios and Maria Gazouli
Biomedicines 2023, 11(7), 1979; https://doi.org/10.3390/biomedicines11071979 - 13 Jul 2023
Cited by 3 | Viewed by 1498
Abstract
Background: Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects both children and adolescents. Symptoms can significantly affect a child’s growth, development, and quality of life, making early diagnosis and effective management crucial. This study focuses on treatment-naïve pediatric [...] Read more.
Background: Pediatric inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease that affects both children and adolescents. Symptoms can significantly affect a child’s growth, development, and quality of life, making early diagnosis and effective management crucial. This study focuses on treatment-naïve pediatric IBD patients and their immediate families to identify the role of the microbiome in disease onset. Methods: Nine families with pediatric IBD were recruited, comprising seven drug-naïve Crohn’s disease (CD) patients and two drug-naïve ulcerative colitis (UC) patients, as well as twenty-four healthy siblings/parents. Fecal samples were collected for 16S ribosomal RNA gene sequencing and bioinformatics analysis. Results: We identified patterns of dysbiosis and hallmark microbial taxa among patients who shared ethnic, habitual, and dietary traits with themselves and their families. In addition, we examined the impact of the disease on specific microbial taxa and how these could serve as potential biomarkers for early detection. Conclusions: Our results suggest a potential role of maternal factors in the establishment and modulation of the early life microbiome, consistent with the current literature, which may have implications for understanding the etiology and progression of IBD. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)
Show Figures

Figure 1

23 pages, 7651 KiB  
Article
Synbiotic Intervention Ameliorates Oxidative Stress and Gut Permeability in an In Vitro and In Vivo Model of Ethanol-Induced Intestinal Dysbiosis
by Dhara Patel, Chirayu Desai, Deepmala Singh, Virupakshi Soppina, Kirti Parwani, Farhin Patel and Palash Mandal
Biomedicines 2022, 10(12), 3285; https://doi.org/10.3390/biomedicines10123285 - 19 Dec 2022
Cited by 4 | Viewed by 1831
Abstract
Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD’s pathophysiology is unknown. However, [...] Read more.
Alcoholic liver disease (ALD) alters gut microbiota and tight junctions, causing bacterial components to enter the portal vein and induce oxidative stress-induced inflammation in the liver. Only corticosteroids and liver transplants are treatment options for severe alcoholic hepatitis. ALD’s pathophysiology is unknown. However, acetaldehyde’s toxic effects cause oxidative stress and intestinal permeability. This study investigates the influence of a synbiotic (a combination of aged garlic extract (AGE) and Lactobacillus rhamnosus MTCC1423) on colonic oxidative stress and inflammation in ALD male Wistar rats and Caco2 cells. MDA measurement by HPLC in CaCo2 cells, blood serum, and colon tissue demonstrated that synbiotic treatment in the ALD model reduces oxidative stress. Further, fecal high-throughput 16S rRNA gene sequencing revealed the microbiome’s shift towards Firmicutes in the synbiotic group compared to ethanol. In addition, DCFDA labeling and H/E staining demonstrate that the synbiotic is beneficial in inhibiting the development of ALD. In the colon, the synbiotic reduces the activation of CYP2E1 and the inflammatory markers TNF-a and IL-6 while elevating the mRNA expression of ZO-1, occludin, and IL-10. Synbiotics colonize Lactobacillus to restore barrier function and microbiota and reduce colon oxidative stress. Thus, a synbiotic combination can be used in ALD treatment. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)
Show Figures

Graphical abstract

Review

Jump to: Research

17 pages, 672 KiB  
Review
Impact of Western Diet and Ultra-Processed Food on the Intestinal Mucus Barrier
by Carmine Stolfi, Teresa Pacifico, Giovanni Monteleone and Federica Laudisi
Biomedicines 2023, 11(7), 2015; https://doi.org/10.3390/biomedicines11072015 - 18 Jul 2023
Cited by 2 | Viewed by 1960
Abstract
The intestinal epithelial barrier plays a key role in the absorption of nutrients and water, in the regulation of the interactions between luminal contents and the underlying immune cells, and in the defense against enteric pathogens. Additionally, the intestinal mucus layer provides further [...] Read more.
The intestinal epithelial barrier plays a key role in the absorption of nutrients and water, in the regulation of the interactions between luminal contents and the underlying immune cells, and in the defense against enteric pathogens. Additionally, the intestinal mucus layer provides further protection due to mucin secretion and maturation by goblet cells, thus representing a crucial player in maintaining intestinal homeostasis. However, environmental factors, such as dietary products, can disrupt this equilibrium, leading to the development of inflammatory intestinal disorders. In particular, ultra-processed food, which is broadly present in the Western diet and includes dietary components containing food additives and/or undergoing multiple industrial processes (such as dry heating cooking), was shown to negatively impact intestinal health. In this review, we summarize and discuss current knowledge on the impact of a Western diet and, in particular, ultra-processed food on the mucus barrier and goblet cell function, as well as potential therapeutic approaches to maintain and restore the mucus layer under pathological conditions. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)
Show Figures

Figure 1

17 pages, 1642 KiB  
Review
RAGE Inhibitors in Neurodegenerative Diseases
by V. Prakash Reddy, Puspa Aryal and Pallavi Soni
Biomedicines 2023, 11(4), 1131; https://doi.org/10.3390/biomedicines11041131 - 09 Apr 2023
Cited by 9 | Viewed by 3421
Abstract
Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of [...] Read more.
Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer’s disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood–brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE–RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE–RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE–RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)
Show Figures

Figure 1

21 pages, 739 KiB  
Review
Gut-on-a-Chip Models: Current and Future Perspectives for HostMicrobial Interactions Research
by Moran Morelli, Dorota Kurek, Chee Ping Ng and Karla Queiroz
Biomedicines 2023, 11(2), 619; https://doi.org/10.3390/biomedicines11020619 - 18 Feb 2023
Cited by 10 | Viewed by 4277
Abstract
The intestine contains the largest microbial community in the human body, the gut microbiome. Increasing evidence suggests that it plays a crucial role in maintaining overall health. However, while many studies have found a correlation between certain diseases and changes in the microbiome, [...] Read more.
The intestine contains the largest microbial community in the human body, the gut microbiome. Increasing evidence suggests that it plays a crucial role in maintaining overall health. However, while many studies have found a correlation between certain diseases and changes in the microbiome, the impact of different microbial compositions on the gut and the mechanisms by which they contribute to disease are not well understood. Traditional pre-clinical models, such as cell culture or animal models, are limited in their ability to mimic the complexity of human physiology. New mechanistic models, such as organ-on-a-chip, are being developed to address this issue. These models provide a more accurate representation of human physiology and could help bridge the gap between clinical and pre-clinical studies. Gut-on-chip models allow researchers to better understand the underlying mechanisms of disease and the effect of different microbial compositions on the gut. They can help to move the field from correlation to causation and accelerate the development of new treatments for diseases associated with changes in the gut microbiome. This review will discuss current and future perspectives of gut-on-chip models to study host-microbial interactions. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies 2.0)
Show Figures

Figure 1

Back to TopTop