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Biomedicines
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Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition
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Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 9958

Special Issue Editors

Dr. Andrea Piccioni

E-Mail Website
Guest Editor
Emergency Medicine Department, University Polyclinic Foundation A. Gemelli, IRCCS (Scientific Institute for Hospitalization and Treatment), 00168 Rome, Italy
Interests: microbiota; gut; dysbiosis; gut microbiome; pathological conditions; metabolic disorders; autoimmune disease; inflammatory disorders; degenerative disease; biomarkers; sepsis; emergency
Special Issues, Collections and Topics in MDPI journals
Dr. Federico Rosa

E-Mail Website
Guest Editor
Department of Emergency Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Interests: microbiota; gut; dysbiosis; gut microbiome; pathological conditions; metabolic disorders; autoimmune disease; inflammatory disorders; degenerative disease; biomarkers; sepsis; emergency
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

One of the most interesting fields of research concerns the gut microbiota.

The human gut microbiota can be considered an organ in its own right, with the peculiar characteristic of developing its basic features from the earliest years of life.

The study of the human microbiota is proving to be of fundamental importance in understanding the development and pathogenesis of numerous pathological conditions, not only those of a gastroenterological nature.

Numerous pieces of evidence highlight a connection between the dysregulation of the gut microbiota and the occurrence of numerous pathological conditions such as inflammatory and metabolic disorders and degenerative and autoimmune diseases.

More and more studies are highlighting the correlation between the gut microbiota and disease occurrence, so it is of paramount importance to stay up-to-date with the latest evidence.

This Special Issue titled “Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition” invites contributions concerning the connection between alterations in the microbiota and the development of diseases affecting the digestive system and beyond.

Authors are also invited to participate with papers regarding the latest evidence on the state of the microbiota in the healthy individual, another of the most interesting and evolving topics.

Dr. Andrea Piccioni
Dr. Federico Rosa
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.

Keywords

  • microbiota
  • gut
  • dysbiosis
  • gut microbiome
  • pathological conditions
  • metabolic disorders
  • autoimmune disease
  • inflammatory disorders
  • degenerative diseases

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Related Special Issue

Published Papers (6 papers)

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Research

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16 pages, 2630 KiB  
Article
Introducing a Novel Personalized Microbiome-Based Treatment for Inflammatory Bowel Disease: Results from NostraBiome’s Internal Validation Study
by Adrian Goldiș, Radu Dragomir, Marina Adriana Mercioni, Christian Goldiș, Diana Sirca, Ileana Enatescu and Oana Belei
Biomedicines 2025, 13(4), 795; https://doi.org/10.3390/biomedicines13040795 - 26 Mar 2025
Viewed by 416
Abstract
Background/Objectives: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is characterized by chronic gut inflammation driven by microbial dysbiosis and immune dysfunction. Current therapies primarily involve anti-inflammatory and immunomodulatory strategies; however, many patients experience an inadequate response or a gradual loss [...] Read more.
Background/Objectives: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is characterized by chronic gut inflammation driven by microbial dysbiosis and immune dysfunction. Current therapies primarily involve anti-inflammatory and immunomodulatory strategies; however, many patients experience an inadequate response or a gradual loss of efficacy over time. This study evaluates the clinical efficacy of personalized microbiome modulation (PMM)—an AI-driven intervention designed to restore microbial balance and improve key treatment outcomes such as symptom control and remission rates. Methods: This was a single-arm, open-label validation trial involving 27 patients with moderate-to-severe IBD who had experienced prior treatment failure. Participants underwent three months of PMM, which included personalized dietary modifications, targeted probiotic supplementation, and antimicrobial interventions based on gut microbiome sequencing. Primary outcomes included stool frequency and consistency as well as inflammatory markers (C-reactive protein and fecal calprotectin), while secondary outcomes assessed nutritional status, metabolic function, and quality of life. Statistical analyses included paired t-tests and repeated measures ANOVA to determine significant changes over time. Results: PMM led to significant clinical improvements, including a 58% reduction in stool frequency (p < 0.001) and improved stool consistency. CRP and fecal calprotectin levels decreased markedly (p < 0.001), suggesting reduced systemic inflammation. Additionally, iron, vitamin B12, and vitamin D deficiencies improved (p < 0.001), alongside weight gain and increased energy levels. Notably, patients on anti-TNF biologics showed enhanced response rates, suggesting potential synergistic effects between microbiome modulation and biologic therapy. Conclusions: This study highlights PMM as a promising adjunctive therapy for IBD, demonstrating benefits across clinical, inflammatory, and metabolic parameters. While findings support the role of microbiome-targeted interventions in disease management, larger randomized controlled trials are required to confirm the long-term efficacy and applicability in broader patient populations. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)
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19 pages, 4632 KiB  
Article
Correction of Batch Effect in Gut Microbiota Profiling of ASD Cohorts from Different Geographical Origins
by Matteo Scanu, Federica Del Chierico, Riccardo Marsiglia, Francesca Toto, Silvia Guerrera, Giovanni Valeri, Stefano Vicari and Lorenza Putignani
Biomedicines 2024, 12(10), 2350; https://doi.org/10.3390/biomedicines12102350 - 15 Oct 2024
Viewed by 1462
Abstract
Background: To date, there have been numerous metataxonomic studies on gut microbiota (GM) profiling based on the analyses of data from public repositories. However, differences in study population and wet and dry pipelines have produced discordant results. Herein, we propose a biostatistical approach [...] Read more.
Background: To date, there have been numerous metataxonomic studies on gut microbiota (GM) profiling based on the analyses of data from public repositories. However, differences in study population and wet and dry pipelines have produced discordant results. Herein, we propose a biostatistical approach to remove these batch effects for the GM characterization in the case of autism spectrum disorders (ASDs). Methods: An original dataset of GM profiles from patients with ASD was ecologically characterized and compared with GM public digital profiles of age-matched neurotypical controls (NCs). Also, GM data from seven case–control studies on ASD were retrieved from the NCBI platform and exploited for analysis. Hence, on each dataset, conditional quantile regression (CQR) was performed to reduce the batch effects originating from both technical and geographical confounders affecting the GM-related data. This method was further applied to the whole dataset matrix, obtained by merging all datasets. The ASD GM markers were identified by the random forest (RF) model. Results: We observed a different GM profile in patients with ASD compared with NC subjects. Moreover, a significant reduction of technical- and geographical-dependent batch effects in all datasets was achieved. We identified Bacteroides_H, Faecalibacterium, Gemmiger_A_73129, Blautia_A_141781, Bifidobacterium_388775, and Phocaeicola_A_858004 as robust GM bacterial biomarkers of ASD. Finally, our validation approach provided evidence of the validity of the QCR method, showing high values of accuracy, specificity, sensitivity, and AUC-ROC. Conclusions: Herein, we proposed an updated biostatistical approach to reduce the technical and geographical batch effects that may negatively affect the description of bacterial composition in microbiota studies. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)
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13 pages, 1439 KiB  
Article
Shotgun Analysis of Gut Microbiota with Body Composition and Lipid Characteristics in Crohn’s Disease
by Péter Bacsur, Tamás Resál, Bernadett Farkas, Boldizsár Jójárt, Zoltán Gyuris, Gábor Jaksa, Lajos Pintér, Bertalan Takács, Sára Pál, Attila Gácser, Kata Judit Szántó, Mariann Rutka, Renáta Bor, Anna Fábián, Klaudia Farkas, József Maléth, Zoltán Szepes, Tamás Molnár and Anita Bálint
Biomedicines 2024, 12(9), 2100; https://doi.org/10.3390/biomedicines12092100 - 14 Sep 2024
Viewed by 1153
Abstract
Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn’s disease (CD). In our cross-sectional study, patients [...] Read more.
Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn’s disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)
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14 pages, 1677 KiB  
Article
Circulating Gut Microbe-Derived Metabolites Are Associated with Hepatocellular Carcinoma
by Rakhee Banerjee, Chase J. Wehrle, Zeneng Wang, Jennifer D. Wilcox, Vinayak Uppin, Venkateshwari Varadharajan, Marko Mrdjen, Courtney Hershberger, Ofer Reizes, Jennifer S. Yu, Justin D. Lathia, Daniel M. Rotroff, Stanley L. Hazen, W. H. Wilson Tang, Federico Aucejo and J. Mark Brown
Biomedicines 2024, 12(9), 1946; https://doi.org/10.3390/biomedicines12091946 - 26 Aug 2024
Cited by 2 | Viewed by 1829
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations [...] Read more.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites. Methods: Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model. Results: In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline (p < 0.001), betaine (p < 0.001), carnitine (p = 0.007), TMA (p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide (p < 0.001), indole-lactic acid (p = 0.038), 5-hydroxyindoleacetic acid (p < 0.0001) and 4-hydroxyphenyllactic acid (p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC (p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis (p = 0.42). Conclusions: Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)
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9 pages, 2842 KiB  
Article
A Rapid and Reliable Spectrofluorimetric Method to Measure the Urinary Lactulose/Mannitol Ratio for Dysbiosis Assessment
by Lorenzo Marino Cerrato, Elisabetta Schiano, Fortuna Iannuzzo, Gian Carlo Tenore, Vincenzo Summa, Maria Daglia, Ettore Novellino and Mariano Stornaiuolo
Biomedicines 2024, 12(7), 1557; https://doi.org/10.3390/biomedicines12071557 - 13 Jul 2024
Viewed by 1254
Abstract
Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn’s disease). Traditional methods used to assess dysbiosis include the dual sugar absorption [...] Read more.
Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn’s disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)
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Review

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35 pages, 2130 KiB  
Review
The Gut Microbiome as a Catalyst and Emerging Therapeutic Target for Parkinson’s Disease: A Comprehensive Update
by Rebecca Kerstens and Paul Joyce
Biomedicines 2024, 12(8), 1738; https://doi.org/10.3390/biomedicines12081738 - 2 Aug 2024
Cited by 1 | Viewed by 2792
Abstract
Parkinson’s Disease is the second most prevalent neurological disorder globally, and its cause is still largely unknown. Likewise, there is no cure, and existing treatments do little more than subdue symptoms before becoming ineffective. It is increasingly important to understand the factors contributing [...] Read more.
Parkinson’s Disease is the second most prevalent neurological disorder globally, and its cause is still largely unknown. Likewise, there is no cure, and existing treatments do little more than subdue symptoms before becoming ineffective. It is increasingly important to understand the factors contributing to Parkinson’s Disease aetiology so that new and more effective pharmacotherapies can be established. In recent years, there has been an emergence of research linking gut dysbiosis to Parkinson’s Disease via the gut–brain axis. Advancements in microbial profiling have led to characterisation of a Parkinson’s-specific microbial signature, where novel treatments that leverage and correct gut dysbiosis are beginning to emerge for the safe and effective treatment of Parkinson’s Disease. Preliminary clinical studies investigating microbiome-targeted therapeutics for Parkinson’s Disease have revealed promising outcomes, and as such, the aim of this review is to provide a timely and comprehensive update of the most recent advances in this field. Faecal microbiota transplantation has emerged as a novel and potential frontrunner for microbial-based therapies due to their efficacy in alleviating Parkinson’s Disease symptomology through modulation of the gut–brain axis. However, more rigorous clinical investigation, along with technological advancements in diagnostic and in vitro testing tools, are critically required to facilitate the widespread clinical translation of microbiome-targeting Parkinson’s Disease therapeutics. Full article
(This article belongs to the Special Issue Advanced Research of Gut Microbiota in Health and Diseases—2nd Edition)
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