Microbiome Dynamics: Advancing Therapeutic Development in Health and Disease

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Microbiology".

Deadline for manuscript submissions: closed (16 February 2026) | Viewed by 1994

Special Issue Editors


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Guest Editor
Department of Medical Science, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Chungnam-do, Republic of Korea
Interests: Microbiome therapeutics, Microbiome biomarker, 'Host-Microbiome-Pathogen' metabolic network

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Guest Editor
Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Chungnam-do, Republic of Korea
Interests: microbiome therapeutics; microbiome biomarker; microbiome-based cosmetics

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Guest Editor
1. Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan-si 31151, Republic of Korea
2. Human Microbiome Medical Research Center (HM·MRC), School of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Sinchang-myeon, Asan-si 31538, Republic of Korea
Interests: microbiome-based therapeutics; microbiome biomarkers; host-pathogen-microbiome interactions; autophagy and microbiome interplay; microbiome in personalized and predictive medicine

Special Issue Information

Dear Colleagues,

The development of microbiome-based therapeutics represents a transformative frontier in biomedical innovation. As our understanding of host–microbiome interactions deepens, microbiota-targeted interventions are increasingly being recognized as promising approaches for managing metabolic, inflammatory, and neurodegenerative diseases, as well as cancer. Moreover, their therapeutic potential is being actively explored for high-risk infectious diseases, including antibiotic-resistant superbugs and tuberculosis, where conventional strategies often fall short.

This Special Issue, entitled “Microbiome Dynamics: Advancing Therapeutic Development in Health and Disease”, encompasses the full continuum of microbiome therapeutic development—from early-stage discovery to clinical validation and real-world application. A key focus is the identification and functional analysis of previously uncharacterized microbial taxa and novel next-generation probiotics (NGPs). Disease-specific metagenomic profiling for microbial biomarker discovery, followed by validation through preclinical models—including animal studies and artificial human microbiome simulators that replicate in vivo gut environments—is highly relevant for the rational design of live biotherapeutics.

We welcome research utilizing multi-omics approaches—metagenomics, metatranscriptomics, metabolomics—to dissect host–microbiome–metabolite interactions. The quantification of bioactive compounds such as short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites offers mechanistic insights into microbiome-driven effects. Studies addressing upstream strain optimization, scalable fermentation, GMP-compliant manufacturing, and downstream clinical trial outcomes for both pharmaceutical and functional food applications are also within scope.

By bridging basic science, advanced modeling systems, and clinical translation, this Special Issue seeks to accelerate the development of precision-targeted microbiome therapeutics for both infectious and non-infectious diseases.

Dr. Hoonhee Seo
Dr. Sukyung Kim
Dr. Md Abdur Rahim
Guest Editors

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Keywords

  • next-generation probiotics (NGPs)
  • microbiome-based therapeutics
  • metagenomics and multi-omics integration
  • microbial biomarkers
  • short-chain fatty acids (SCFAs)
  • artificial human microbiome simulators
  • GMP-scale production
  • clinical translation

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Published Papers (2 papers)

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Research

17 pages, 1452 KB  
Article
Preliminary Characterization of Skin Microbiota and Mycobiota in Atopic Dermatitis by Metagenomic and Culture-Based Analyses
by Federica Carraturo, Michela Salamone, Martina Annunziata, Eugenia Veronica Di Brizzi, Caterina Mariarosaria Giorgio, Arianna Petrillo, Ludovica Fedi, Angela Maione, Marco Guida and Emilia Galdiero
Life 2026, 16(4), 690; https://doi.org/10.3390/life16040690 - 20 Apr 2026
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Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by several factors, including immune system imbalance, impairment of the epidermal barrier, and alterations in the composition of the gut and skin bacterial and fungal microbiota. This study combines metagenomic sequencing and culture-based [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by several factors, including immune system imbalance, impairment of the epidermal barrier, and alterations in the composition of the gut and skin bacterial and fungal microbiota. This study combines metagenomic sequencing and culture-based methods to explore the impact of probiotic supplementation on the cutaneous microbiota and mycobiota of AD patients. Twenty-five adults diagnosed with AD were enrolled, and skin swabs were analyzed to characterize microbial diversity and load. Culturomic analyses identified 42 bacterial and 6 fungal species, confirming Staphylococcus aureus and Candida parapsilosis as predominant taxa. High-throughput sequencing revealed Staphylococcus spp. and Malassezia spp. as dominant genera, with notable interindividual variability. While probiotic use did not significantly influence bacterial diversity, it was associated with higher richness and evenness in fungal communities, as shown by alpha and beta diversity metrics. Malassezia restricta was more prevalent among probiotic users, whereas Candida parapsilosis and Rhodotorula mucilaginosa were enriched in non-users. These findings indicate an association between probiotic use and differences in the composition and diversity of the skin mycobiota compared with the bacterial microbiota, suggesting that fungal communities may be more responsive to probiotic-associated factors. Integrating metagenomic and culturomic approaches offers valuable insights into the complex interactions among host factors, microbial communities, and probiotic use in AD, paving the way for targeted microbiome-based therapeutic strategies. Full article
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24 pages, 2232 KB  
Article
Longitudinal Fecal Short-Chain Fatty Acid Trajectories in Preterm Infants with Early-Onset Neonatal Sepsis: A Pilot Study
by Evgenii Kukaev, Olga Krogh-Jensen, Natalia Starodubtseva, Alisa Tokareva, Irina Nikitina, Anna Lenyushkina, Vladimir Frankevich and Gennady Sukhikh
Life 2025, 15(12), 1943; https://doi.org/10.3390/life15121943 - 18 Dec 2025
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Abstract
Background: Early-onset neonatal sepsis (EONS), defined as systemic infection occurring within the first 72 hours of life, remains a major cause of morbidity and mortality in preterm infants. Increasing evidence indicates that the gut may play an active role in systemic inflammation, yet [...] Read more.
Background: Early-onset neonatal sepsis (EONS), defined as systemic infection occurring within the first 72 hours of life, remains a major cause of morbidity and mortality in preterm infants. Increasing evidence indicates that the gut may play an active role in systemic inflammation, yet the temporal behavior of fecal short-chain fatty acids (SCFAs) during EONS has not been characterized. SCFAs and branched-chain fatty acids (BCFAs) are key microbial metabolites involved in epithelial maturation and immune regulation and may provide a non-invasive window into early inflammatory vulnerability. Methods: This pilot prospective longitudinal cohort study enrolled 49 preterm infants (≤32 weeks’ gestation) originally identified as at high risk for necrotizing enterocolitis (NEC) and subsequently stratified into EONS and non-sepsis groups. Serial stool samples were collected at predefined timepoints (TPs; TP1 ≈ 3 days of life [DoL], TP2 ≈ 7 DoL, TP3 ≈ 14 DoL, TP4 ≈ 21 DoL, and TP5 ≈ 28 DoL). Samples were analyzed using gas chromatography–mass spectrometry (GC–MS) to quantify a panel of 12 SCFAs, including BCFAs and medium-chain fatty acids (MCFAs). Both absolute concentrations and relative fractions were evaluated, with emphasis on ratio-based metrics (e.g., acetic/propionic acid ratio) and timepoint-specific group contrasts, complemented by partial least squares discriminant analysis (PLS–DA). Results: At the earliest sampling window (TP1), infants with EONS exhibited distinct early changes in SCFA composition, including a significantly lower median relative fraction of acetic acid (86.6% vs. 94.5% in non-sepsis), while several non-acetate components—including propionic, valeric, and branched-chain acids—were relatively enriched. Acetate-to-non-acetate ratios were markedly reduced in EONS (e.g., acetic/propionic and acetic/isobutyric ratios), indicating an early shift away from acetate dominance. PLS–DA at TP1 demonstrated partial separation between groups, with acetic-acid depletion and non-acetate enrichment among the strongest contributors to discrimination. By later TPs, these early differences narrowed to a small subset of BCFA-related ratios and largely attenuated by the end of the first month. Conclusions: In this pilot cohort of preterm infants, EONS was associated with early, structured alterations in fecal SCFA profiles, characterized by reduced acetic-acid dominance and relative enrichment of non-acetate acids. Dynamic, ratio-based assessment proved more informative than absolute concentrations alone, revealing transient intestinal metabolic signatures accompanying systemic infection. These findings provide the first longitudinal evidence of gut metabolic involvement in EONS and lay the groundwork for larger, multi-center studies integrating SCFA trajectories with microbiome and immune profiling to refine early risk stratification for systemic infection in high-risk neonatal populations. Full article
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