Unveiling Human Microbiome Composition and Functions to Improve Health and Disease Research

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (15 March 2026) | Viewed by 3540

Special Issue Editor


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Guest Editor
1. Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy
2. CEINGE-Biotecnologie Avanzate Franco Salvatore, 80145 Napoli, Italy
Interests: next generation sequencing; genomics; cancer genomics; hereditary cancers; metagenomics; human microbiome; molecular diagnostics
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Special Issue Information

Dear Colleagues,

The human microbiome, an intricate ecosystem of microorganisms residing in and on the human body, has emerged as a cornerstone of biomedical research over the past decade. With advances in sequencing technologies and computational biology, we have begun to uncover the profound influence of the microbiome on virtually every aspect of human health and disease. From metabolic and immune system regulation to its role in neurological and psychological well-being, the microbiome offers unprecedented opportunities to understand the complex interplay between humans, and in particular human genes, and their microbial counterparts.

This Special Issue, "Unveiling Human Microbiome Composition and Functions to Improve Health and Disease Research", is dedicated to exploring the genetic underpinnings of microbiome functions and their integration with host genomics. This Special Issue highlights cutting-edge methodologies, tools, and conceptual frameworks that leverage the microbiome to address critical challenges in health research and clinical practice. As the field continues to evolve, researchers are employing innovative strategies to interrogate microbiome composition and function, establish causal relationships, and develop targeted interventions.

The articles in this Special Issue should cover the diverse range of approaches—from in vitro and in vivo models to advanced computational techniques and translational applications—with a strong emphasis on genetic and genomic perspectives. Collectively, they will emphasize the importance of interdisciplinary collaboration, integrating microbiology, bioinformatics, immunology, and clinical sciences to propel our understanding of microbiome-mediated mechanisms and their implications for health and disease management.

This introduction highlights the importance of harnessing the human microbiome to revolutionize healthcare. By fostering dialogue across disciplines and embracing the complexity of host–microbe interactions, we aim to illuminate pathways for precision medicine and transformative public health initiatives. We invite you to delve into this Special Issue and join us in exploring the exciting frontiers of microbiome research. Research and review articles on these aspects are encouraged. The manuscripts will, as always, be subjected to examination by specialized reviewers to guarantee their scientific acceptability.

Dr. Valeria D’Argenio
Guest Editor

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Keywords

  • human microbiome
  • health and disease
  • precision medicine
  • host–microbe interactions
  • translational research
  • metagenomics
  • multi-omics approaches

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Published Papers (2 papers)

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Research

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16 pages, 1206 KB  
Article
Exercise, APOE Genotype, and Testosterone Modulate Gut Microbiome–Cognition Associations in Prostate Cancer Survivors
by Jacob Raber, Abigail O’Niel, Kristin D. Kasschau, Alexandra Pederson, Naomi Robinson, Carolyn Guidarelli, Christopher Chalmers, Kerri Winters-Stone and Thomas J. Sharpton
Genes 2025, 16(12), 1507; https://doi.org/10.3390/genes16121507 - 16 Dec 2025
Cited by 2 | Viewed by 1147
Abstract
Background: Men treated with androgen deprivation therapy (ADT) for prostate cancer are at risk for cognitive decline. Patient genetics and endocrine state may shape gut microbiome features that relate to cognition. Methods: We studied a subsample of 79 prostate cancer survivors with prior [...] Read more.
Background: Men treated with androgen deprivation therapy (ADT) for prostate cancer are at risk for cognitive decline. Patient genetics and endocrine state may shape gut microbiome features that relate to cognition. Methods: We studied a subsample of 79 prostate cancer survivors with prior ADT exposure previously enrolled in a randomized controlled exercise trial comparing three training modalities (strength training, Tai Chi training, or stretching control) who completed an additional food-frequency questionnaire and remote Montreal Cognitive Assessment (MoCA) and provided saliva and stool for APOE genotyping, salivary testosterone, and 16S rRNA sequencing. We used beta regression for MoCA (scaled 0–1), linear models for testosterone, alpha diversity regressions, PERMANOVA for beta diversity, and DESeq2 for genus-level differential abundance, with false-discovery correction. Results: Compared to post-stretching control, post-strength training testing was associated with higher MoCA scores whereas post-Tai Chi testing was not. APOE ε4 carriers exhibited a greater testosterone increase with strength training than non-carriers. Testosterone, and its interactions with exercise modality and APOE ε2 status, was related to presence/absence-based community structure; APOE ε4 interacted with exercise intervention to influence alpha diversity. At the genus level, exercise was linked to lower levels of Bacteroidota taxa (including Muribaculaceae) and higher levels of Enterobacteriaceae; APOE ε4 status was linked to higher Megamonas and lower Rikenellaceae RC9 levels; and higher salivary testosterone levels were linked to higher Prevotellaceae taxa and Succinivibrio levels. Higher MoCA scores were associated with lower abundances of several Firmicutes genera. Conclusions: Endocrine state and APOE genotype may condition the gut microbiome’s response to exercise intervention in ADT-treated prostate cancer survivors, with downstream associations with cognition. These findings could inform precision survivorship strategies pairing strength training with genotype- and hormone-informed microbiome monitoring to optimize cognitive performance. Full article
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Review

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18 pages, 1229 KB  
Review
Composition and Function of Gut Microbiome: From Basic Omics to Precision Medicine
by Yan Ma, Lamei Wang, Haitao Hu, Audrey Ruei-En Shieh, Edward Li, Dongdong He, Lin He, Zhong Liu, Thant Mon Paing, Xinhua Chen and Yangchun Cao
Genes 2026, 17(1), 116; https://doi.org/10.3390/genes17010116 - 22 Jan 2026
Cited by 3 | Viewed by 1777
Abstract
The gut microbiome is defined as the collective assembly of microbial communities inhabiting the gut, along with their genes and metabolic products. The gut microbiome systematically regulates host metabolism, immunity, and neuroendocrine homeostasis via interspecies interaction networks and inter-organ axes. Given the importance [...] Read more.
The gut microbiome is defined as the collective assembly of microbial communities inhabiting the gut, along with their genes and metabolic products. The gut microbiome systematically regulates host metabolism, immunity, and neuroendocrine homeostasis via interspecies interaction networks and inter-organ axes. Given the importance of the gut microbiome to the host, this review integrates the composition, function, and genetic basis of the gut microbiome with host genomics to provide a systematic overview of recent advances in microbiome–host interactions. This encompasses a complete technological pipeline spanning from in vitro to in vivo models to translational medicine. This technological pipeline spans from single-bacterium CRISPR editing, organoid–microbiome co-culture, and sterile/humanized animal models to multi-omics integrated algorithms, machine learning causal inference, and individualized probiotic design. It aims to transform microbiome associations into precision intervention strategies that can be targeted and predicted for clinical application through interdisciplinary research, thereby providing the cornerstone of a new generation of precision treatment strategies for cancer, metabolic, and neurodegenerative diseases. Full article
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