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Gut Dysbiosis: Molecular Mechanisms and Therapies
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Gut Dysbiosis: Molecular Mechanisms and Therapies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 20152

Special Issue Editors

Dr. Federica Laudisi

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
Dr. Carmine Stolfi

E-Mail Website
Guest Editor
Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy
Interests: colorectal cancer; immunotherapy; inflammatory bowel diseases; anti-cancer drugs
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).

You may choose our Joint Special Issue in Biomedicines.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Published Papers (5 papers)

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Research

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13 pages, 2724 KiB  
Article
Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion
by Cristina Santiso-Bellón, Roberto Gozalbo-Rovira, Javier Buesa, Antonio Rubio-del-Campo, Nazaret Peña-Gil, Noemi Navarro-Lleó, Roberto Cárcamo-Calvo, María J. Yebra, Vicente Monedero and Jesús Rodríguez-Díaz
Int. J. Mol. Sci. 2022, 23(18), 10643; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810643 - 13 Sep 2022
Cited by 2 | Viewed by 1891
Abstract
Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement [...] Read more.
Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1–3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies)
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26 pages, 8203 KiB  
Article
Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations
by Laimdota Zizmare, Christina N. Boyle, Sabrina Buss, Sandrine Louis, Laura Kuebler, Ketki Mulay, Ralf Krüger, Lara Steinhauer, Isabelle Mack, Manuel Rodriguez Gomez, Kristina Herfert, Yvonne Ritze and Christoph Trautwein
Int. J. Mol. Sci. 2022, 23(3), 1126; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031126 - 20 Jan 2022
Cited by 6 | Viewed by 3773
Abstract
Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB [...] Read more.
Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies)
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Review

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40 pages, 641 KiB  
Review
Human Gut Microbiota in Health and Selected Cancers
by Aleksandra Sędzikowska and Leszek Szablewski
Int. J. Mol. Sci. 2021, 22(24), 13440; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413440 - 14 Dec 2021
Cited by 23 | Viewed by 5652
Abstract
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role [...] Read more.
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto’s thyroidis and Graves’ disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies)
19 pages, 359 KiB  
Review
Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood
by Adi Eindor-Abarbanel, Genelle R. Healey and Kevan Jacobson
Int. J. Mol. Sci. 2021, 22(22), 12506; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212506 - 19 Nov 2021
Cited by 15 | Viewed by 3697
Abstract
There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients [...] Read more.
There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients with IBD, suggesting that IBD results from alterations in the interactions between intestinal microbes and the host’s mucosal immune system. These studies have been the impetus for the development of new therapeutic approaches targeting the gut microbiome, such as nutritional therapies, probiotics, fecal microbiota transplant and beneficial metabolic derivatives. Innovative technologies can further our understanding of the role the microbiome plays as well as help to evaluate how the different approaches in microbiome modulation impact clinical responses in adult and pediatric patients. In this review, we highlight important microbiome studies in patients with IBD and their response to different microbiome modulation therapies, and describe the differences in therapeutic response between pediatric and adult patient cohorts. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies)
22 pages, 1134 KiB  
Review
Mining the Microbiome and Microbiota-Derived Molecules in Inflammatory Bowel Disease
by Matthijs Bekkers, Bojan Stojkovic and Gerard E. Kaiko
Int. J. Mol. Sci. 2021, 22(20), 11243; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011243 - 18 Oct 2021
Cited by 7 | Viewed by 4155
Abstract
The intestinal microbiota is a complex community that consists of an ecosystem with a dynamic interplay between bacteria, fungi, archaea, and viruses. Recent advances in model systems have revealed that the gut microbiome is critical for maintaining homeostasis through metabolic digestive function, immune [...] Read more.
The intestinal microbiota is a complex community that consists of an ecosystem with a dynamic interplay between bacteria, fungi, archaea, and viruses. Recent advances in model systems have revealed that the gut microbiome is critical for maintaining homeostasis through metabolic digestive function, immune regulation, and intestinal barrier integrity. Taxonomic shifts in the intestinal microbiota are strongly correlated with a multitude of human diseases, including inflammatory bowel disease (IBD). However, many of these studies have been descriptive, and thus the understanding of the cause and effect relationship often remains unclear. Using non-human experimental model systems such as gnotobiotic mice, probiotic mono-colonization, or prebiotic supplementation, researchers have defined numerous species-level functions of the intestinal microbiota that have produced therapeutic candidates for IBD. Despite these advances, the molecular mechanisms responsible for the function of much of the microbiota and the interplay with host cellular processes remain areas of tremendous research potential. In particular, future research will need to unlock the functional molecular units of the microbiota in order to utilize this untapped resource of bioactive molecules for therapy. This review will highlight the advances and remaining challenges of microbiota-based functional studies and therapeutic discovery, specifically in IBD. One of the limiting factors for reviewing this topic is the nascent development of this area with information on some drug candidates still under early commercial development. We will also highlight the current and evolving strategies, including in the biotech industry, used for the discovery of microbiota-derived bioactive molecules in health and disease. Full article
(This article belongs to the Special Issue Gut Dysbiosis: Molecular Mechanisms and Therapies)
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