本文介绍了Phenomics期刊2025年第一期（人体肠道微生物组专刊）收录文章合集，文章概览如下，请查收！

（Phenomics期刊2025年第一期封面图）

01

Human Gut Microbiome Researches Over the Last Decade: Current Challenges and Future Directions

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论文DOI链接：

https://doi.org/10.1007/s43657-023-00131-z

引用格式：

Wu, H., Forslund, S., Wang, Z. et al. Human Gut Microbiome Researches Over the Last Decade: Current Challenges and Future Directions. Phenomics 5, 1–7 (2025). https://doi.org/10.1007/s43657-023-00131-z

Summary

Despite the rapid advances in gut microbiome research, there remain many challenges that need to be addressed. To tackle these obstacles, it is imperative to establish international collaborations and consortia. Such collaborations would bring together researchers from different fields and regions, fostering the convergence research model, which is the hallmark of the 'third revolution' in life sciences. Such collaborative effort is also critical for advancing our comprehension of the gut microbiome and for translating this knowledge into better health outcomes for patients. Step by step, piece by piece, we should be able to achieve the Yin-Yang balance between our gut microbes and us humans.

Eight selected challenges we are facing in human gut microbiome researches

02

Embracing Interpersonal Variability of Microbiome in Precision Medicine

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论文DOI链接：

https://doi.org/10.1007/s43657-024-00201-w

引用格式：

Zhou, X., Chen, X., Davis, M.M. et al. Embracing Interpersonal Variability of Microbiome in Precision Medicine. Phenomics 5, 8–13 (2025). https://doi.org/10.1007/s43657-024-00201-w

Conclusion

In conclusion, one of the essential new frontiers of biomedicine is the exploration of interpersonal variability, a critical aspect frequently overlooked in traditional animal-based studies. This endeavor is not only foundational for developing precise, personalized treatment modalities but also for deepening our collective understanding of human biology.

A strategic approach to achieving this involves the initiation of longitudinal, observational human studies, distinctly crafted to probe specific scientific questions. Importantly, these studies should be conducted across multiple centers and span international borders to maximize the diversity of variables considered, thereby enhancing the robustness and generalizability of the findings. Comparing microbiome populations between more and less industrialized societies, between racial groups, and even between humans and non-human primates will reveal important information regarding the dynamics of host-microbiome interaction.

Furthermore, the execution of meta-analyses and comparative analyses across different datasets will be instrumental in obtaining global insights, allowing a more comprehensive understanding of the interplay between genetic, environmental, and microbial determinants of health and disease. As we continue to advance beyond the foundation established by the HMP and related cohorts, we eagerly anticipate a surge in research efforts embracing this inclusive, collaborative framework. The convergence of these methodologies promises to usher in a new era of medical science, characterized by highly personalized, effective healthcare solutions informed by an in depth understanding of interpersonal variability.

Comparison between animal experiments and clinical trials using live bacteria as therapeutics

03

Relational Stability: A New Strategy for Defining the Human Core Microbiome

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论文DOI链接：

https://doi.org/10.1007/s43657-025-00236-7

引文格式：

Zhao, L. Relational Stability: A New Strategy for Defining the Human Core Microbiome. Phenomics 5, 14–17 (2025). https://doi.org/10.1007/s43657-025-00236-7

Summary

Relational stability redefines our understanding of the core microbiome, offering a transformative lens through which to study and apply microbiome science. By emphasizing stable relationships as the foundation of the gut microbial ecosystem, this approach moves beyond the limitations of taxonomic overlap, capturing the dynamic and functional interdependencies that sustain host health. The Two Competing Guilds (TCG) model exemplifies this framework, highlighting the ecological balance between health-promoting and disease-driving microbe (Wu et al. 2024; Zhao et al. 2018; Zhang et al. 2015; Xiao et al. 2014). Its applications, from precision medicine to AI modeling, underscore the potential of relational stability to reshape research and interventions across disciplines.

However, the promise of relational stability is only beginning to be realized. Researchers must now embrace this paradigm shift, applying relational stability not only to microbiome studies but also to broader complex adaptive systems. This requires collaboration across fields, integrating insights from ecology, systems biology, and computational science to refine methodologies and expand applications. For microbiome researchers, this means prioritizing the identification of stably connected genome pairs and using these relationships to inform biomarker discovery, therapeutic design, and predictive modeling.

Relational stability offers more than a theoretical framework; it is a practical tool for understanding and restoring balance in systems under stress, from disrupted microbiomes to fragmented ecosystems. By adopting relational stability as a guiding principle, researchers can uncover universal patterns of resilience and functionality, driving innovation and improving outcomes in health care, technology, and beyond. The time to act is now—by focusing on stable relationships, we open new doors to understanding the intricate connections that sustain life and its remarkable adaptability.

04

Development of Next Generation Probiotics for Cardiometabolic Diseases

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论文DOI链接：

https://doi.org/10.1007/s43657-025-00230-z

引文格式：

Khan, M.T., Bäckhed, F. Development of Next Generation Probiotics for Cardiometabolic Diseases. Phenomics 5, 18–22 (2025). https://doi.org/10.1007/s43657-025-00230-z

Summary

Targeting the gut microbiota holds great potential for improving human health, and metagenomics studies in the last two decades have identified a broad range of bacteria that might be candidates for development of next-generation probiotics. It is important to acknowledge that the vast majority of bacteria identified in metagenomics surveys lacks cultured representatives, which highlights the importance of isolation of bacteria that can be further investigated for their potential in improving host health. Further development of animal models may be used for exploring efficacy and mechanisms. Once a potential bacterial strain has been developed it will be essential to determine how to optimize both the production, for example through optimizing oxygen tolerance, but also by supplying specific fibers and/or micronutrients and vitamins that may improve the function of the bacteria.

Strategy for isolation and development of next generation probiotics 

05

 Precision Dietary Intervention: Gut Microbiome and Meta-metabolome as Functional Readouts

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论文DOI链接：

https://doi.org/10.1007/s43657-024-00193-7

引文格式：

Luo, J., Wang, Y. Precision Dietary Intervention: Gut Microbiome and Meta-metabolome as Functional Readouts. Phenomics 5, 23–50 (2025). https://doi.org/10.1007/s43657-024-00193-7

Abstract

Gut microbiome, the group of commensals residing within the intestinal tract, is closely associated with dietary patterns by interacting with food components. The gut microbiome is modifiable by the diet, and in turn, it utilizes the undigested food components as substrates and generates a group of small molecule-metabolites that addressed as “meta-metabolome” in this review. Profiling and mapping of meta-metabolome could yield insightful information at higher resolution and serve as functional readouts for precision nutrition and formation of personalized dietary strategies. For assessing the meta-metabolome, sample preparation is important, and it should aim for retrieval of gut microbial metabolites as intact as possible. The meta-metabolome can be investigated via untargeted and targeted meta-metabolomics with analytical platforms such as nuclear magnetic resonance spectroscopy and mass spectrometry. Employing flux analysis with meta-metabolomics using available database could further elucidate metabolic pathways that lead to biomarker discovery. In conclusion, integration of gut microbiome and meta-metabolomics is a promising supplementary approach to tailor precision dietary intervention. In this review, relationships among diet, gut microbiome, and meta-metabolome are elucidated, with an emphasis on recent advances in alternative analysis techniques proposed for nutritional research. We hope that this review will provide information for establishing pipelines complementary to traditional approaches for achieving precision dietary intervention.

Relationship among diet, gut microbiome, and meta-metabolome

06

 Implication of Gut Mycobiome and Virome in Type-2 Diabetes Mellitus: Uncovering the Hidden Players

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论文DOI链接：

https://doi.org/10.1007/s43657-024-00199-1

引文格式：

Kriti, M., Ojha, R., Singh, S. et al. Implication of Gut Mycobiome and Virome in Type-2 Diabetes Mellitus: Uncovering the Hidden Players. Phenomics 5, 51–64 (2025). https://doi.org/10.1007/s43657-024-00199-1

Abstract

Type-2 diabetes mellitus (T2DM) is a global epidemic with significant societal costs. The gut microbiota, including its metabolites, plays a pivotal role in maintaining health, while gut dysbiosis is implicated in several metabolic disorders, including T2DM. Although data exists on the relationship between the gut bacteriome and metabolic disorders, further attention is needed for the mycobiome and virome. Recent advancements have begun to shed light on these connections, offering potential avenues for preventive measures. However, more comprehensive investigations are required to untangle the interrelations between different microbial kingdoms and their role in T2DM development or mitigation. This review presents a simplified overview of the alterations in the gut bacteriome in T2DM and delves into the current understanding of the mycobiome and virome’s role in T2DM, along with their interactions with the cohabiting bacteriome. Subsequently, it explores into the age-related dynamics of the gut microbiome and the changes observed in the microbiome composition with the onset of T2DM. Further, we explore the basic workflow utilized in gut microbiome studies. Lastly, we discuss potential therapeutic interventions in gut microbiome research, which could contribute to the amelioration of the condition, serve as preventive measures, or pave the way towards personalized medicine.

Overview and outcome of cross-kingdom interaction between bacteria, fungi and viruses in T2DM development and advancement

07

Comparative Analysis of Growth Dynamics and Relative Abundances of Gut Microbiota Influenced by Ketogenic Diet

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论文DOI链接：

https://doi.org/10.1007/s43657-025-00228-7

引文格式：

Tang, M., Zhang, Z., Lin, L. et al. Comparative Analysis of Growth Dynamics and Relative Abundances of Gut Microbiota Influenced by Ketogenic Diet. Phenomics 5, 65–75 (2025). https://doi.org/10.1007/s43657-025-00228-7

Abstract

Although the compositional alterations of gut bacteria in ketogenic diet (KD) have been intensively investigated, the causal relationship between this extreme diet and the microbiota changes is not fully understood. Here, we studied the growth dynamics of intestinal bacteria in KD. We used the CoPTR method to calculate the peak-to-trough ratio (PTR) based on metagenomic sequencing data, serving as an indicator of bacterial growth rates. Notably, Akkermansia muciniphila, a bacterium strongly linked to the therapeutic benefits of KD, exhibited one of the highest growth rates, aligning with its markedly elevated abundance. Our findings also revealed discrepancies in the change patterns of CoPTR values and relative abundances for various bacteria across different diet groups, some of which might be attributed to the exceptionally high or low growth rates of specific species. For some of the species demonstrating obvious differences in growth rates between KD and standard diet, we conducted in vitro culture experiments, supplementing them with diverse nutritional sources to elucidate the underlying mechanisms. The integrative analysis of bacterial abundance and growth dynamics can help deepen our understanding of the gut microbiota changes caused by KD and the therapeutic effects of this special diet.

Schematic illustration of the animal models construction, samples collection and subsequent analysis performed in this study

08

Impact of DNA Extraction Methods on Gut Microbiome Profiles: A Comparative Metagenomic Study

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论文DOI链接：

https://doi.org/10.1007/s43657-025-00232-x

引文格式：

Pu, Y., Zhou, X., Cai, H. et al. Impact of DNA Extraction Methods on Gut Microbiome Profiles: A Comparative Metagenomic Study. Phenomics 5, 76–90 (2025). https://doi.org/10.1007/s43657-025-00232-x

Abstract

In gut microbial research, DNA extraction remarkably influences study outcomes and biological interpretations. Rapid advancements in the research scale and technological upgrades necessitate evaluating new methods to ensure reliability and precision in microbial community profiling. We systematically evaluated the performance of eight recent and commonly used extraction methods using a microbial mock community (MMC) and fecal samples from two healthy volunteers, incorporating bacterial, archaeal, and fungal constituents. Performance metrics included nucleic acid assessment, microbial profile assessment, and scalability for large-scale studies, leveraging shotgun metagenomics for in-depth analysis. Despite variations in DNA quantity and quality, all methods yielded sufficient DNA for shotgun metagenomic sequencing. In the MMC microbial profile assessment, the QIAamp PowerFecal pro Kit (PF) and DNeasy PowerSoil HTP kit (PS) methods exhibited higher similarity with the theoretical composition and lower variability across technical replicates compared to other methods. For fecal samples, the extraction method accounted for 21.4% of the overall microbiome variation and significantly affected the abundances of 32% of detected microbial species. Methods using mechanical lysis with small beads, such as PF and PS, demonstrated better efficiency, indicated by increased microbial diversity in extracting DNA from Gram-positive bacteria. Furthermore, the PF and PS methods are notably simple to execute and automation-friendly, though relatively costly. Our study underscores the importance of maintaining consistency in DNA extraction methods for reliable comparative metagenomic analyses. We recommend PF and PS methods as optimal for expansive gut metagenomic research, emphasizing the critical role of mechanical lysis in DNA extraction.

Overview of study flow

09

Topology of gut Microbiota Network and Guild-Based Analysis in Chinese Adults

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论文DOI链接：

https://doi.org/10.1007/s43657-024-00211-8

引文格式：

Fu, J., Yu, D., Zheng, W. et al. Topology of gut Microbiota Network and Guild-Based Analysis in Chinese Adults. Phenomics 5, 91–108 (2025). https://doi.org/10.1007/s43657-024-00211-8

Abstract

Gut microbiota with co-abundant behaviors is considered belonging to the same guild in micro-ecosystem. In this study, we established co-abundance networks of operational taxonomic units (OTUs) among 2944 Chinese adults from the Shanghai Men’s and Women’s Health Studies and observed a positive connection-dominated scale-free network using Sparse Correlations for Compositional data (SparCC). The closeness centrality was negatively correlated with other degree-based topological metrics in the network, indicating the isolated modularization of the bacteria. A total of 130 guilds were constructed, with a high modularity of 0.68, and retaining more diversity of OTUs than genus classification. The scores of guild structure similarity for comparisons between all, the healthy and the unhealthy subjects were higher than those derived from randomized permutations, suggesting a robust guild structure. We further used the constructed 130 guilds as the aggregation units to identify gut microbiota that may be associated with type 2 diabetes, and found that the OTUs in 21 significant guilds relevant to diabetes belonged to 19 of 41 (46.3%) previously reported genera (derived from Disbiome database), while only 10 (24.4%) showed different abundances between diabetes patients and healthy subjects in genus-based analysis. Our study reveals modularization of gut microbiota as guilds in Chinese populations, and demonstrates advantages of guild-based analysis in identifying diabetes-related gut bacteria. The analytical method based on microbial networks should be widely used to deepen our understanding of the role of gut microbiota in human health.

Study outline and analysis flow

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