All Issue

2025 Vol.55, Issue 1

Review Article

Gut Microbes Libraries: A Key Resource for Current Gut Microbiome Research
Ayyaz Khan1
,
Sura Kim1
,
Seong-Tshool Hong1*
1Department of Biomedical Sciences and Institute for Medical Science, Jeonbuk National University Medical School, Jeonju 54907, Republic of Korea
*seonghong@jbnu.ac.kr
31 March 2025. pp. 1-9
PDF XML Citation
Abstract

Complex microbial communities shape the dynamics of the human gut, influencing digestion, immunity, and overall health. Advances in DNA sequencing, multi-omics technologies, and data analysis have significantly improved microbiome studies by enhancing taxonomic resolution and controlling false discovery rates. However, a major limitation remains—the lack of a cultured, representative library of human gut microbes. Existing isolate and genome collections are still limited, especially in strain-level diversity, for most microbes in the human gut. Notably, over 70% of species in the Unified Human Gastrointestinal Genome (UHGG) collection lack cultured representatives. This unknown microbial ‘dark matter’ significantly limits our understanding of the functions of the gut microbiome and its host interactions. To advance our knowledge of the gut microbiome through proof-of-concept research that satisfies Koch’s postulates and supports mechanistic investigations, establishing a comprehensive gut microbe library is essential. However, the scarcity of pure gut microbe cultures worldwide makes constructing a comprehensive gut microbe library challenging. Here we discuss the importance of constructing a comprehensive gut microbial library. It outlines key challenges in establishing a gut microbe library, including sample collection, culture media, and long-term storage. Additionally, it explores the potential applications of a comprehensive gut microbe library in microbiome research.

Keywords
Culturomics
Gut microbes
Library
Microbiome
Microbiota
References
1

Lkhagva E, Chung HJ, Ahn JS, Hong ST. Host Factors Affect the Gut Microbiome More Significantly than Diet Shift. Microorganisms. 2021;9(12):2520.

10.3390/microorganisms912252034946120PMC8707884
2

Groot HE, van de Vegte YJ, Verweij N, Lipsic E, Karper JC, van der Harst P. Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study. Sci Rep. 2020;10(1):14771.

10.1038/s41598-020-70724-532901066PMC7479141
3

Zhai C, Ahn JS, Islam MM, Lkhagva E, Chung HJ, Hong ST. Comparative Analysis of Original and Replaced Gut Microbiomes within Same Individuals Identified the Intestinal Microbes Associated with Weight Gaining. Microorganisms. 2022;10(5):1062.

10.3390/microorganisms1005106235630504PMC9144321
4

Cani PD. Human gut microbiome: hopes, threats and promises. Gut. 2018;67(9):1716-1725.

10.1136/gutjnl-2018-31672329934437PMC6109275
5

Chen Y, Feng W, Ye K, Guo L, Xia H, Guan Y, et al. Application of Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infectious Pathogens From Bronchoalveolar Lavage Samples. Front Cell Infect Microbiol. 2021;11:541092.

10.3389/fcimb.2021.54109233777827PMC7991794
6

Chen X, D'Souza R, Hong ST. The role of gut microbiota in the gut-brain axis: current challenges and perspectives. Protein Cell. 2013;4(6):403-414.

10.1007/s13238-013-3017-x23686721PMC4875553
7

Wang WL, Xu SY, Ren ZG, Tao L, Jiang JW, Zheng SS. Application of metagenomics in the human gut microbiome. World J Gastroenterol. 2015;21(3):803-814.

10.3748/wjg.v21.i3.80325624713PMC4299332
8

Ito T, Sekizuka T, Kishi N, Yamashita A, Kuroda M. Conventional culture methods with commercially available media unveil the presence of novel culturable bacteria. Gut Microbes. 2019;10(1):77-91.

10.1080/19490976.2018.149126530118379PMC6363062
9

Lagier JC, Hugon P, Khelaifia S, Fournier PE, La Scola B, Raoult D. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota. Clin Microbiol Rev. 2015;28(1):237-264.

10.1128/CMR.00014-1425567229PMC4284300
10

Raymond F, Boissinot M, Ouameur AA, Déraspe M, Plante PL, Kpanou SR, Culture-enriched human gut microbiomes reveal core and accessory resistance genes. Microbiome. 2019;7(1):56.

10.1186/s40168-019-0669-730953542PMC6451232
11

Lagier JC, Khelaifia S, Alou MT, Ndongo S, Dione N, Hugon P, et al. Culture of previously uncultured members of the human gut microbiota by culturomics. Nat Microbiol. 2016;1:16203.

10.1038/nmicrobiol.2016.20327819657
12

Lau JT, Whelan FJ, Herath I, Lee CH, Collins SM, et al. Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling. Genome Med. 2016;8(1):72.

10.1186/s13073-016-0327-727363992PMC4929786
13

Naud S, Khelaifia S, Mbogning Fonkou MD, Dione N, Lagier JC, Raoult D. Proof of concept of culturomics use of time of care. Front Cell Infect Microbiol. 2020;10:524769.

10.3389/fcimb.2020.52476933330116PMC7719802
14

Lagier JC, Edouard S, Pagnier I, Mediannikov O, Drancourt M, Raoult D. Current and past strategies for bacterial culture in clinical microbiology. Clin Microbiol Rev. 2015;28(1):208-236.

10.1128/CMR.00110-1425567228PMC4284306
15

Vartoukian SR, Palmer RM, Wade WG. Strategies for culture of 'unculturable' bacteria. FEMS Microbiol Lett. 2010;309(1):1-7.

10.1111/j.1574-6968.2010.02000.x20487025
16

Liu C, Du MX, Abuduaini R, Yu HY, Li DH, Wang YJ, et al. Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank. Microbiome. 2021;9(1):119.

10.1186/s40168-021-01064-334020714PMC8140505
17

Hasman H, Saputra D, Sicheritz-Ponten T, Lund O, Svendsen CA, Frimodt-Møller N, et al. Rapid whole-genome sequencing for detection and characterization of microorganisms directly from clinical samples. J Clin Microbiol. 2014;52(1):139-146.

10.1128/JCM.02452-1324172157PMC3911411
18

Hitch TCA, Afrizal A, Riedel T, Kioukis A, Haller D, Lagkouvardos I, et al. Recent advances in culture-based gut microbiome research. Int J Med Microbiol. 2021;311(3):151485.

10.1016/j.ijmm.2021.15148533689954
19

Neville BA, Forster SC, Lawley TD. Commensal Koch's postulates: establishing causation in human microbiota research. Curr Opin Microbiol. 2018;42:47-52.

10.1016/j.mib.2017.10.00129112885
20

Lin X, Hu T, Chen J, Liang H, Zhou J, Wu Z, et al. The genomic landscape of reference genomes of cultivated human gut bacteria. Nat Commun. 2023;14(1):1663.

10.1038/s41467-023-37396-x36966151PMC10039858
21

Park SK, Lee CW, Park DI, Woo HY, Cheong HS, Shin HC, et al. Detection of SARS-CoV-2 in fecal samples from patients with asymptomatic and mild COVID-19 in Korea. Clin Gastroenterol Hepatol. 2021;19(7):1387-1394. e2.

10.1016/j.cgh.2020.06.00532534042PMC7286243
22

Wang M, Lkhagva E, Kim S, Zhai C, Islam MM, Kim HJ, et al. The gut microbe pair of Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270 confers complete protection against SARS-CoV-2 infection by activating CD8+ T cell-mediated immunity. Gut Microbes. 2024;16(1):2342497.

10.1080/19490976.2024.234249738635321PMC11028030
23

Pamer EG. Gut microbes fend off harmful bacteria by depriving them of nutrients. Nature. 2024;633(8031):774-775.

10.1038/d41586-024-02803-w39294279
24

Kim CY, Lee M, Yang S, Kim K, Yong D, Kim HR, et al. Human reference gut microbiome catalog including newly assembled genomes from under-represented Asian metagenomes. Genome Med. 2021;13(1):134.

10.1186/s13073-021-00950-734446072PMC8394144
25

Kim CY, Lee M, Yang S, Kim K, Yong D, Kim HR, et al. Human reference gut microbiome comprising 5,414 prokaryotic species, including newly assembled genomes from under-represented Asian metagenomes. bioRxiv. 2020:2020.11.09.375873.

10.1101/2020.11.09.375873
26

Liu C, Du MX, Abuduaini R, Yu HY, Li DH, Wang YJ, et al. Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank. Microbiome. 2021;9(1):119.

10.1186/s40168-021-01064-334020714PMC8140505
27

GMBANK The World's Largest Gut Microbe Bank. Available at https://www.gmbank.org/. [accessed on 17 February 2025].

28

Almeida A, Nayfach S, Boland M, Strozzi F, Beracochea M, Shi ZJ, et al. A unified catalog of 204,938 reference genomes from the human gut microbiome. Nat Biotechnol. 2021;39(1):105-114.

10.1038/s41587-020-0603-332690973PMC7801254
29

Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449(7164):804-810.

10.1038/nature0624417943116PMC3709439
30

Forster SC, Kumar N, Anonye BO, Almeida A, Viciani E, Stares MD, et al. A human gut bacterial genome and culture collection for improved metagenomic analyses. Nat Biotechnol. 2019;37(2):186-192.

10.1038/s41587-018-0009-730718869PMC6785715
31

Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA, Stares MD, et al. Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation. Nature. 2016;533(7604):543-546.

10.1038/nature1764527144353PMC4890681
32

Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, et al. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proc Natl Acad Sci U S A. 2011;108(15):6252-6257.

10.1073/pnas.110293810821436049PMC3076821
33

Poyet M, Groussin M, Gibbons SM, Avila-Pacheco J, Jiang X, Kearney SM, et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nat Med. 2019;25(9):1442-1452.

10.1038/s41591-019-0559-331477907
34

Chang Y, Hou F, Pan Z, Huang Z, Han N, Bin L, et al. Optimization of culturomics strategy in human fecal samples. Front Microbiol. 2019;10:2891.

10.3389/fmicb.2019.0289131921067PMC6927924
35

Wornell K, Pardesi B, Lee K, Boycheva S, Roberton AM, White WL. High‐throughput Method for Novel Medium Development for Culture of Anaerobic Gut Bacteria. Curr Protoc. 2022;2(7):e463.

10.1002/cpz1.46335822953
36

Lagier JC, Dubourg G, Million M, Cadoret F, Bilen M, Fenollar F, et al. Culturing the human microbiota and culturomics. Nat Rev Microbiol. 2018;16(9):540-550.

10.1038/s41579-018-0041-029937540
37

Poulsen CS, Kaas RS, Aarestrup FM, Pamp SJ. Standard sample storage conditions have an impact on inferred microbiome composition and antimicrobial resistance patterns. Microbiol Spectr. 2021;9(2):e0138721.

10.1128/Spectrum.01387-2134612701PMC8510183
38

Correa Lopes B, Turck J, Tolbert MK, Giaretta PR, Suchodolski JS, Pilla R. Prolonged storage reduces viability of Peptacetobacter (Clostridium) hiranonis and core intestinal bacteria in fecal microbiota transplantation preparations for dogs. Front Microbiol. 2025;15:1502452.

10.3389/fmicb.2024.150245239839105PMC11747423
39

Bellali S, Bou Khalil J, Fontanini A, Raoult D, Lagier JC. A new protectant medium preserving bacterial viability after freeze drying. Microbiol Res. 2020;236:126454.

10.1016/j.micres.2020.12645432200250
40

Park H, Yeo S, Ryu CB, Huh CS. A streamlined culturomics case study for the human gut microbiota research. Sci Rep. 2024;14(1):20361.

10.1038/s41598-024-71370-x39223323PMC11368911
41

D'Elia D, Truu J, Lahti L, Berland M, Papoutsoglou G, Ceci M, et al. Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action. Front Microbiol. 2023;14:1257002.

10.3389/fmicb.2023.125700237808321PMC10558209
42

Li P, Luo H, Ji B, Nielsen J. Machine learning for data integration in human gut microbiome. Microb Cell Fact. 2022;21(1):241.

10.1186/s12934-022-01973-436419034PMC9685977
43

Kim N, Ma J, Kim W, Kim J, Belenky P, Lee I. Genome-resolved metagenomics: a game changer for microbiome medicine. Exp Mol Med. 2024;56(7):1501-1512.

10.1038/s12276-024-01262-738945961PMC11297344
44

Hernández Medina R, Kutuzova S, Nielsen KN, Johansen J, Hansen LH, Nielsen M, et al. Machine learning and deep learning applications in microbiome research. ISME Commun. 2022;2(1):98.

10.1038/s43705-022-00182-937938690PMC9723725
45

Ali T, Ahmed S, Aslam M. Artificial intelligence for antimicrobial resistance prediction: challenges and opportunities towards practical implementation. Antibiotics (Basel). 2023;12(3):523.

10.3390/antibiotics1203052336978390PMC10044311
46

Westfall S, Carracci F, Estill M, Zhao D, Wu QL, Shen L, et al. Optimization of probiotic therapeutics using machine learning in an artificial human gastrointestinal tract. Sci Rep. 2021;11(1):1067.

10.1038/s41598-020-79947-y33441743PMC7806704
47

Estaki M, Jiang L, Bokulich NA, McDonald D, González A, Kosciolek T, et al. QIIME 2 enables comprehensive end‐to‐end analysis of diverse microbiome data and comparative studies with publicly available data. Curr Protoc Bioinformatics. 2020;70(1):e100.

10.1002/cpbi.10032343490PMC9285460
48

Liang Q, Bible PW, Liu Y, Zou B, Wei L. DeepMicrobes: taxonomic classification for metagenomics with deep learning. NAR Genom Bioinform. 2020;2(1):lqaa009.

10.1093/nargab/lqaa00933575556PMC7671387
Information
  • Publisher :The Korean Society for Microbiology and The Korean Society of Virology
  • Publisher(Ko) :대한미생물학회‧대한바이러스학회
  • Journal Title :JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • Volume : 55
  • No :1
  • Pages :1-9
  • Received Date : 2025-02-19
  • Revised Date : 2025-03-11
  • Accepted Date : 2025-03-12
  • DOI :https://doi.org/10.4167/jbv.2025.55.1.001
Journal Informaiton JOURNAL OF BACTERIOLOGY AND VIROLOGY JOURNAL OF BACTERIOLOGY AND VIROLOGY
  • NRF
  • 임플란트학회 전용 배너
  • KOFST
  • crossref crossmark
  • crossref cited-by
  • crossref funder-registry
  • crosscheck
  • orcid
  • open access
  • ccl
Journal Informaiton Journal Informaiton - close