REVIEW article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1626002
This article is part of the Research TopicThe Role of Gut Microbes and Their Metabolites in Metabolic Diseases: Mechanisms and Therapeutic TargetsView all 9 articles
Enhanced Metagenomic Strategies for Elucidating the Complexities of Gut Microbiota: A Review
Provisionally accepted
Xinru Li1
Haiyan Lu2*- 1Anorectal Surgery, Changsha Hospital of Traditional Chinese Medicine (Changsha Eighth Hospital), Changsha, 410099, China, Changsha, China
- 2Hunan University of Chinese Medicine, Changsha, China
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The human gastrointestinal tract (GIT) is inhabited by a heterogeneous and dynamic microbial community that influences host health at multiple levels both metabolically, immunologically and via neurological pathways. Though the gut microbiota-overwhelmingly Bacteroidetes and Firmicutes-has essential functions in nutrient metabolism, immune regulation, and resistance to pathogens, its dysbiosis is likewise associated with pathologies, such as inflammatory bowel disease (IBD), obesity, type 2 diabetes (T2D), and neurodegenerative diseases. While conventional metagenomic techniques laid the groundwork for understanding microbial composition, next-generation enhanced metagenomic techniques permit an unprecedented resolution in exploring the functional and spatial complexity of gut communities. Advanced frameworks such as high-throughput sequencing, bioinformatic and multi-omics technologies are expanding the understanding of microbial gene regulation, metagenomic pathways, and host-microbe communication. Beyond taxonomic profiling, they map niche-specific activities of gut microbiota along a dichotomy of facultative mutualism, evidenced by relations of beneficial symbionts, represented here by Enterobacteriaceae. In this review, we critically consider the latest approaches (e.g., long-read sequencing, single-cell metagenomics and AI-guided annotation) that mitigate biases stemming from DNA extraction, sequencing depth and functional inference.
Keywords: gut microbiome, Metagenomics, Beneficial and Harmful microbes, Long-read sequencing, Multi-omics integration
Received: 09 May 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Li and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haiyan Lu, Hunan University of Chinese Medicine, Changsha, China
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