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Microorganisms
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Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational...
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Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational Perspectives

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Gut Microbiota".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 3268

Special Issue Editors

Dr. Maria Rosaria Matera

E-Mail Website
Guest Editor
Department of Pediatric Emergencies, Misericordia Hospital, Grosseto, Italy
Interests: gut microbiome; probiotics
Dr. Lorenzo Drago

E-Mail Website
Guest Editor
Department of Biochemical Sciences for Health, University of Milan, Milan, Italy
Interests: microbiota and probiotics; prosthetic and joint infections; biofilm implant related infections; osteomyelitis; diagnosis for bone-joint infections; antimicrobials and antimicrobial devices
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The gut microbiota plays a pivotal role in shaping host physiology, immune function, metabolism, and neurodevelopment. Increasing evidence highlights how alterations in microbiota composition and function contribute to a wide spectrum of acute and chronic diseases, while also influencing responses to pharmacological and nutritional interventions. Despite rapid advances in microbiome research, significant gaps remain in translating mechanistic insights into biologically grounded and personalized strategies.

This Special Issue aims to provide an updated and integrative overview of gut microbiota–host interactions, with particular emphasis on microbial mechanisms, functional traits, and translational perspectives. We welcome original research articles, reviews, and conceptual papers exploring host–microbe interactions at molecular, cellular, metabolic, immunological, and neurobiological levels, with a specific focus on microbial functions and strain-specific activities.

Topics of interest include, but are not limited to, the following: microbial resilience and resistance to external perturbations (e.g., antibiotics, diet, environmental stressors); intrinsic and functional microbial traits; host genetic and epigenetic factors influencing microbiota composition; microbiota-derived metabolites and signaling pathways; and rational strategies for microbiota modulation. Particular attention will be given to mechanistically grounded frameworks that move beyond descriptive associations, offering biologically informed models capable of guiding experimental, clinical, and translational research.

By integrating basic science with clinical and systems-level approaches, this Special Issue aims to foster a more coherent and mechanistically driven understanding of gut microbiota–host interactions and their relevance for personalized and precision medicine.

Dr. Maria Rosaria Matera
Dr. Lorenzo Drago
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 250 words) can be sent to the Editorial Office for assessment.

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. Microorganisms 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 2700 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

  • gut microbiota
  • host–microbe interactions
  • microbiota resilience
  • antibiotic–microbiota interactions
  • microbial metabolism
  • microbial functional traits
  • microbiota–gut–brain axis
  • precision microbiota modulation
  • translational microbiome research
  • functional microbiomics

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Published Papers (5 papers)

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Research

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28 pages, 19843 KB  
Article
Functional Shifts in Gut Microbiota and Associated Metabolites Suggest Gut–Brain Axis Dysregulation in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS)
by Shabana M. Shaik, Gabriele Schiro, Daniel Laubitz, Juliette C. Madan, Connor P. Kelley, Michael Daines, Sydney A. Rice, Fayez K. Ghishan and Pawel R. Kiela
Microorganisms 2026, 14(5), 1036; https://doi.org/10.3390/microorganisms14051036 - 2 May 2026
Viewed by 201
Abstract
Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host–microbiome interactions in modulating neuro-immune functions via gut–brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly [...] Read more.
Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) are characterized by neuropsychiatric symptoms linked to immune dysregulation. Emerging evidence highlights the role of host–microbiome interactions in modulating neuro-immune functions via gut–brain axis signaling; however, its contribution to PANDAS pathophysiology remains poorly understood. Methods: We conducted microbiome analysis from samples collected across multiple sites of PANDAS patients including nasal, throat and stool. We performed an integrated multi-omics analysis of stool samples from pediatric PANDAS cases and healthy controls, including discordant twin pairs. Microbial composition and function were assessed using 16S rRNA gene sequencing, shotgun metagenomics, while untargeted metabolomic profiling was performed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Results: PANDAS cases exhibited reduced alpha diversity and significantly altered beta diversity compared to controls, indicating shifts in gut microbial composition. Shotgun metagenomic analysis revealed differential enrichment of functional pathways, including diminished quorum sensing, altered gamma-aminobutyric acid (GABA) biosynthesis, and microbial degradation processes. Multiple gut–brain modules (GBMs) and gut metabolic modules (GMMs) associated with neurotransmission, transport activities and metabolism were significantly perturbed in PANDAS. Metabolomic profiling showed reduced functional diversity and distinct clustering of metabolic profiles, with differential abundance of amino acids, bile acids, and neuroactive compounds. Integrative analysis further identified disrupted microbe–metabolite networks allied to gut–brain signaling. Conclusions: Our findings reveal significant functional shifts in gut microbiota composition, functional capacity and metabolite profile in PANDAS, suggesting dysregulation of the gut–brain axis signaling. This study provides a foundation for development of microbiome-based biomarkers and therapeutic strategies for pediatric neuropsychiatric disorders. Full article
(This article belongs to the Special Issue Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational Perspectives)
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26 pages, 15038 KB  
Article
Akkermansia muciniphila NND9 Mitigates Ulcerative Colitis by Ameliorating the Gut Barrier via Suppressing DR5 Expression in a Mouse Model
by Xin-Yu Gao, Yan Wang, Yu-Hui Wang, Hao Yu, Liang Liu, Xing-Hua Zhang, Hong-Tao Xu, Yao Meng, Randal N. Johnston, Gui-Rong Liu and Shu-Lin Liu
Microorganisms 2026, 14(5), 1002; https://doi.org/10.3390/microorganisms14051002 - 29 Apr 2026
Viewed by 239
Abstract
Ulcerative colitis (UC) is a type of inflammatory bowel disease without curative therapeutics. Recent studies demonstrate that Akkermansia muciniphila exerts mitigating effects on UC, but the underlying mechanisms remain unclear. In this study, we isolated a strain of A. muciniphila, designated NND9, [...] Read more.
Ulcerative colitis (UC) is a type of inflammatory bowel disease without curative therapeutics. Recent studies demonstrate that Akkermansia muciniphila exerts mitigating effects on UC, but the underlying mechanisms remain unclear. In this study, we isolated a strain of A. muciniphila, designated NND9, from the feces of DSS-induced ulcerative colitis model mice and investigated its effects on UC of the mouse model. NND9 significantly alleviated UC severity in the mice by restoring gut barrier integrity through improving colonic mucus layer thickness, mitigating goblet cell depletion, and halting epithelial cell death. Mechanistically, NND9 suppressed the expression of the Tnfrsf10b gene encoding death receptor 5 (DR5) on the surface of colonic epithelial cells. Additionally, NND9 inhibited the phosphorylation of kinase 3 (RIPK3) and the pseudokinase mixed-lineage kinase domain-like protein (MLKL) associated with the necrotic apoptosis pathway, thereby reducing gut epithelial cell death. NND9 also markedly ameliorated the gut microbiome of the colitis mice. Untargeted metabolomics analysis demonstrated that NND9 modulated both tryptophan and bile acid metabolism. In conclusion, NND9 exhibits curative effects on UC by resolving inflammatory reactions of the gut mucosa through the DR5-RIPK3/p-RIPK3-MLKL/p-MLKL pathway and redressing gut dysbiosis. This study provides valuable information for the development of innovative therapeutic strategies for the treatment of UC. Full article
(This article belongs to the Special Issue Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational Perspectives)
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16 pages, 2329 KB  
Article
Microbial Biomarkers for the Prevention and Diagnosis of Alcoholic Liver Disease
by Goo Hyun Kwon, Hyunjoon Park, Hyeong Seop Kim, Ki Kwang Oh, Jung A Eom, Kyeong Jin Lee, Min Ju Kim, Minsoo Kim, Jeong Su Kim, Sang Hak Han, Young Lim Ham and Ki Tae Suk
Microorganisms 2026, 14(2), 449; https://doi.org/10.3390/microorganisms14020449 - 12 Feb 2026
Viewed by 648
Abstract
Alterations in gut microbiota are closely associated with alcohol-associated liver disease (ALD) progression. We aimed to identify ALD-related bacterial strains with therapeutic or diagnostic potential. Human fecal samples were analyzed to screen candidate microbes, and an ALD mouse model was used to evaluate [...] Read more.
Alterations in gut microbiota are closely associated with alcohol-associated liver disease (ALD) progression. We aimed to identify ALD-related bacterial strains with therapeutic or diagnostic potential. Human fecal samples were analyzed to screen candidate microbes, and an ALD mouse model was used to evaluate their effects. We also assessed bacterial DNA levels in blood to explore diagnostic utility. Lactobacillus helveticus and L. lactis treatment improved gut dysbiosis and reduced hepatic inflammation and endotoxemia. In contrast, Veillonella dispar, which is significantly enriched in ALD patients, had no beneficial effects in vivo. Instead, V. dispar abundance in blood distinguished ALD patients from controls with an area under the ROC curve of 0.815. These findings suggest that L. helveticus and L. lactis may be effective probiotics for ALD, while V. dispar may serve as a non-invasive diagnostic biomarker. Targeting microbiota may offer a new approach for ALD prevention and diagnosis. Full article
(This article belongs to the Special Issue Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational Perspectives)
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17 pages, 10285 KB  
Article
Microcin C7 Prevents Cyclophosphamide-Induced Immunosuppression and Intestinal Injury by Modulating T-Cell Differentiation and Gut Microbiota Composition in Mice
by Jianfei Zhao, Zhongqian Lu, Jialin Wu, Li Wang, Jinxiu Huang and Feiyun Yang
Microorganisms 2026, 14(2), 350; https://doi.org/10.3390/microorganisms14020350 - 3 Feb 2026
Viewed by 555
Abstract
Microcin C7 (McC7) is a ribosomally synthesized antimicrobial peptide that has emerged as a promising candidate due to its dual antibacterial and immunomodulatory activities. This study evaluated the preventive effect of McC7 against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. An immunosuppression model was [...] Read more.
Microcin C7 (McC7) is a ribosomally synthesized antimicrobial peptide that has emerged as a promising candidate due to its dual antibacterial and immunomodulatory activities. This study evaluated the preventive effect of McC7 against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. An immunosuppression model was established by intraperitoneal CTX injection in mice, which were randomly allocated into five groups (n = 15): a negative control, a CTX model group, and three McC7 treatment groups receiving dietary McC7 at 100, 200, or 400 mg/kg both before and during CTX exposure. Body weight and feed intake were monitored throughout the study. Organ indices, serum biochemical parameters, immune and antioxidant markers, and intestinal morphology were assessed. Splenic T-cell subsets were analyzed by flow cytometry, and gut microbiota composition was evaluated by 16S rRNA sequencing. McC7 supplementation significantly attenuated the CTX-induced reduction in body weight, feed intake, and organ indices, ameliorated markers of hepatic and renal injury, and restored the splenic CD4+/CD8+ T-cell ratio. McC7 enhanced intestinal mucosal barrier integrity, increased the abundance of beneficial bacteria such as Candidatus Arthromitus and ASF356, and reduced the abundance of the potentially pathogenic genus Bilophila. In conclusion, our results demonstrate that McC7 alleviates CTX-induced immunosuppression by regulating T-cell differentiation, maintaining cytokine homeostasis, and modulating gut microbial composition to support intestinal health. Full article
(This article belongs to the Special Issue Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational Perspectives)
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Review

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21 pages, 767 KB  
Review
Probiotics and Antibiotics: From Empirical Practice to a Biological Rationale for Targeted Choice During Antibiotic Therapy
by Mariarosaria Matera, Valentina Biagioli, Stefano Leo and Lorenzo Drago
Microorganisms 2026, 14(4), 763; https://doi.org/10.3390/microorganisms14040763 - 27 Mar 2026
Viewed by 1273
Abstract
Antibiotic therapy represents one of the strongest ecological perturbations of the human gut microbiota, inducing rapid and often prolonged alterations in community structure, metabolic activity, and functional resilience. While the use of probiotics to mitigate antibiotic-associated dysbiosis is widely adopted in clinical practice, [...] Read more.
Antibiotic therapy represents one of the strongest ecological perturbations of the human gut microbiota, inducing rapid and often prolonged alterations in community structure, metabolic activity, and functional resilience. While the use of probiotics to mitigate antibiotic-associated dysbiosis is widely adopted in clinical practice, probiotic selection is still largely empirical and insufficiently grounded in biological compatibility with specific antibiotic pressures. In this conceptual review, antibiotics are reframed not merely as antimicrobial agents, but as ecological forces that shape microbial survival, quiescence, and recolonization dynamics. We propose a biologically informed framework that distinguishes genetic antibiotic resistance from functional or ecological insensitivity, highlighting how microbial traits, such as the absence or inaccessibility of the antibiotic target, metabolic state, sporulation, and cellular architecture, influence the persistence of probiotics during antibiotic exposure. By integrating the mechanisms of action of antibiotics with key physiological and structural features of probiotic microorganisms, we develop a conceptual framework aimed at rationalizing the compatibility of probiotics and antibiotics. This framework does not imply clinical efficacy but provides an interpretative tool to guide hypothesis generation, experimental validation, and the design of future targeted probiotic strategies. A more ecologically grounded approach to probiotic selection may ultimately improve microbiota support during antibiotic therapy and advance personalized microbiome modulation. Full article
(This article belongs to the Special Issue Advances in Gut Microbiota–Host Interactions: Microbial Mechanisms, Modulators, and Translational Perspectives)
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