Gut microbiota, a complex microbial community in the human intestine, are vital for digestion, nutrient absorption, and immune regulation, maintaining gut micro-ecological balance. Accurate detection of its composition, structure, and function is crucial for understanding the relationship between health and disease, early disease diagnosis, personalized treatment, and exploring disease mechanisms. Traditional detection methods such as culture and conventional polymerase chain reaction (PCR) have limitations. Culture methods, which rely on specific media, struggle with anaerobic and fastidious microbes and thus have long detection times. Conventional PCR is complex, has low throughput, and is prone to contamination, not meeting the need for efficient, accurate, and high-throughput analysis. Microfluidic technology, manipulating small fluid volumes through microscale channels, offers new opportunities with advantages such as simple operation, low reagent consumption, and fast analysis. This review encompasses the microfluidic-based detection methods of gut microbiota in recent years. It expounds on the principles of these methods and analyzes their achievements, advantages, and limitations in practical applications. The aim is to provide multi-dimensional technical references for relevant research, thereby promoting the application of this technology in the research of gut microbiota and the management of gut diseases.
| [1] |
Y. Li, Z. Huang, L. Xu, Y. Fan, J. Ping, G. Li, Y. Chen, C. Yu, Q. Wang, T. Song, T. Lin, M. Liu, Y. Xu, N. Ai, X. Meng, Q. Qiao, H. Ji, Z. Qin, S. Jin, N. Jiang, M. Wang, S. Shu, F. Zhang, W. Zhang, G.-H. Liu, L. Chen, L. Jiang, Nat. Methods 2025, 22, 1199.
|
| [2] |
W. Postek, P. Garstecki, Acc. Chem. Res. 2022, 55, 605.
|
| [3] |
H. Cai, W. Tong, L. Wei, M. Song, Y. Zhao, K. Li, H. Zhang, C. Yang, P. Cheng, Commun. Mater. 2024, 5, 278.
|
| [4] |
W. J. Watterson, M. Tanyeri, A. R. Watson, C. M. Cham, Y. Shan, E. B. Chang, A. M. Eren, S. Tay, eLife 2020, 9, e56998.
|
| [5] |
J. Riti, G. Sutra, T. Naas, H. Volland, S. Simon, K. Perez-Toralla, Biosens. Bioelectron. 2024, 257, 116301.
|
| [6] |
D. Yang, Z. Yu, M. Zheng, W. Yang, Z. Liu, J. Zhou, L. Huang, Lab Chip 2023, 23, 3961.
|
| [7] |
A. S. Tauzin, M. R. Pereira, L. D. Van Vliet, P.-Y. Colin, E. Laville, J. Esque, S. Laguerre, B. Henrissat, N. Terrapon, V. Lombard, M. Leclerc, J. Doré, F. Hollfelder, G. Potocki-Veronese, Microbiome 2020, 8, 141.
|
| [8] |
M.-Z. Jiang, H.-Z. Zhu, N. Zhou, C. Liu, C.-Y. Jiang, Y. Wang, S.-J. Liu, Sci. Rep. 2022, 12, 18145.
|
| [9] |
G. Cai, F. Xu, B. Chen, X. Li, J. Huang, S. Mi, Lab Chip 2023, 23, 349.
|
| [10] |
N. Jin, L. Xue, Y. Ding, Y. Liu, F. Jiang, M. Liao, Y. Li, J. Lin, Biosens. Bioelectron. 2023, 220, 114844.
|
| [11] |
Y. Zou, M. Liu, Z. Gao, Y. Xue, J. Qiu, H. Zhang, X. Li, C. Zhang, B. Shu, Small 2025, 21, 2411417.
|
| [12] |
B. Li, B. Lin, Y. Wang, Y. Shi, W. Zeng, Y. Zhao, Y. Gu, C. Liu, H. Gao, H. Cheng, X. Zheng, G. Xiang, G. Wang, P. Liu, Nat. Commun. 2024, 15, 8770.
|
| [13] |
Z. Li, Y. Wang, Z. Gao, S. Sekine, Q. You, S. Zhuang, D. Zhang, S. Feng, Y. Yamaguchi, Anal. Chim. Acta 2023, 1251, 340995.
|
| [14] |
X. Hu, C. Lin, G. Li, T. Jiang, J. Shen, J. Microbiol. Methods 2023, 211, 106785.
|
| [15] |
G. Boularias, N. Azzag, C. Galon, L. Šimo, H.-J. Boulouis, S. Moutailler, Pathogens 2021, 10, 362.
|
| [16] |
E. Huang, Y. Wang, N. Yang, B. Shu, G. Zhang, D. Liu, Anal. Bioanal. Chem. 2021, 413, 1787.
|
| [17] |
D. Lee, T. S. Seo, Heliyon 2025, 11, e42183.
|
| [18] |
L. Chen, C. Zhang, V. Yadav, A. Wong, S. Senapati, H.-C. Chang, Sci. Rep. 2023, 13, 184.
|
| [19] |
J. Shen, J. Zheng, Z. Li, Y. Liu, F. Jing, X. Wan, Y. Yamaguchi, S. Zhuang, Lab Chip 2021, 21, 3742.
|
| [20] |
E. A. Ottesen, J. W. Hong, S. R. Quake, J. R. Leadbetter, Science 2006, 314, 1464.
|
| [21] |
J. Zhai, Y. Liu, W. Ji, X. Huang, P. Wang, Y. Li, H. Li, A. H.-H. Wong, X. Zhou, P. Chen, L. Wang, N. Yang, C. Chen, H. Chen, P.-I. Mak, C.-X. Deng, R. Martins, M. Yang, T.-Y. Ho, S. Yi, H. Yao, Y. Jia, Nat. Commun. 2024, 15, 4363.
|
| [22] |
M. Krupovic, D. H. Bamford, Science 2011, 333, 45.
|
| [23] |
Y. Wouters, D. Dalloyaux, A. Christenhusz, H. M. J. Roelofs, H. F. Wertheim, C. P. Bleeker-Rovers, R. H. Te Morsche, G. J. A. Wanten, Microb. Biotechnol. 2020, 13, 657.
|
| [24] |
Y. Luo, X. Cui, E. Cheruba, Y. K. Chua, C. Ng, R. Z. Tan, K. Tan, L. F. Cheow, Small Methods 2022, 6, 2200185.
|
| [25] |
K. Hu, W. Yin, Y. Wang, L. Xia, Y. Bai, Q. Zhu, J. Yin, Y. Mu, W. Jin, Sens. Actuators B Chem. 2024, 405, 135110.
|
| [26] |
J. Liu, R. Fu, S. Zhang, J. Hou, H. Ma, S. Hu, H. Li, Y. Zhang, W. Wang, B. Qiao, B. Zang, X. Min, F. Zhang, J. Du, S. Yan, Biosens. Bioelectron. 2024, 256, 116282.
|
| [27] |
H. Bai, J. Hu, T. Liu, L. Wan, C. Dong, D. Luo, F. Li, Z. Yuan, Y. Tang, T. Chen, S. Wang, H. Gou, Y. Zhou, B. Ying, J. Huang, W. (Walter) Hu, Lab Chip 2025, 25, 1552.
|
| [28] |
S. Li, Y. Zhang, J. Liu, X. Wang, C. Qian, J. Wang, L. Wu, C. Dai, H. Yuan, C. Wan, J. Li, W. Du, X. Feng, Y. Li, P. Chen, B. Liu, Small 2024, 20, 2401848.
|
| [29] |
T. Khajvand, P. Huang, L. Li, M. Zhang, F. Zhu, X. Xu, M. Huang, C. Yang, Y. Lu, Z. Zhu, Lab Chip 2021, 21, 4823.
|
| [30] |
K. Zhao, X. Shen, H. Liu, Z. Lin, J. Li, S. Chen, F. Liu, K. Huang, J. Cao, X. Liu, C. Shen, L. Yu, Y. Zhao, L. Zhao, Y. Li, D. Hu, J. Huang, X. Lu, D. Gu, JAMA Cardiol. 2024, 9, 233.
|
| [31] |
S. Sandhu, J. A. Schouten, J. Thompson, M. Davis, T. D. H. Bugg, Analyst 2012, 137, 1130.
|
| [32] |
S. Ramachandran, M. Singhal, K. McKenzie, J. Osborn, A. Arjyal, S. Dongol, S. Baker, B. Basnyat, J. Farrar, C. Dolecek, G. Domingo, P. Yager, B. Lutz, Diagnostics 2013, 3, 244.
|
| [33] |
T.-C. Lu, Y.-J. Yang, Y. Zhong, Q.-Z. Qiu, Z.-H. Chen, Y.-Z. Chen, Y. Lei, A.-L. Liu, Biosens. Bioelectron. 2024, 243, 115772.
|
| [34] |
K. Wang, S. Wang, S. Margolis, J. M. Cho, E. Zhu, A. Dupuy, J. Yin, S.-K. Park, C. E. Magyar, O. B. Adeyiga, K. S. Jensen, J. A. Belperio, F. Passam, P. Zhao, T. K. Hsiai, Sci. Adv. 2024, 10, eadq6778.
|
| [35] |
Z. Tak For Yu, H. Guan, M. Ki Cheung, W. M. McHugh, T. T. Cornell, T. P. Shanley, K. Kurabayashi, J. Fu, Sci. Rep. 2015, 5, 11339.
|
| [36] |
B. Song, J. Wang, Z. Yan, Z. Liu, X. Pan, Y. Zhang, X. Zhang, Bioengineered 2020, 11, 1137.
|
| [37] |
C.-H. Han, J. Jang, Lab Chip 2021, 21, 184.
|
| [38] |
G. Cai, L. Zheng, M. Liao, Y. Li, M. Wang, N. Liu, J. Lin, Microchim. Acta 2019, 186, 757.
|
| [39] |
B. Dai, S. You, K. Wang, Y. Long, J. Chen, N. Upreti, J. Peng, L. Zheng, C. Chang, T. J. Huang, Y. Guan, S. Zhuang, D. Zhang, Sci. Adv. 2025, 11, eadq2494.
|
| [40] |
J. Chung, J. S. Kang, J. S. Jurng, J. H. Jung, B. C. Kim, Biosens. Bioelectron. 2015, 67, 303.
|
| [41] |
Y. Ito, R. Sasaki, S. Asari, T. Yasuda, H. Ueda, T. Kitaguchi, Small 2023, 19, 2207943.
|
| [42] |
J. S. Kang, K. S. Lee, S. S. Kim, G.-N. Bae, J. H. Jung, Lab Chip 2014, 14, 244.
|
| [43] |
P. Sabhachandani, S. Sarkar, P. C. Zucchi, B. A. Whitfield, J. E. Kirby, E. B. Hirsch, T. Konry, Microchim. Acta 2017, 184, 4619.
|
| [44] |
J. Cama, M. Voliotis, J. Metz, A. Smith, J. Iannucci, U. F. Keyser, K. Tsaneva-Atanasova, S. Pagliara, Lab Chip 2020, 20, 2765.
|
| [45] |
G. Xing, N. Li, H. Lin, Y. Shang, Q. Pu, J.-M. Lin, Talanta 2023, 253, 123980.
|
| [46] |
D. Rodoplu, C.-S. Chang, C.-Y. Kao, C.-H. Hsu, Talanta 2021, 230, 122291.
|
| [47] |
X. Shi, T. Mao, X. Huang, H. Shi, K. Jiang, R. Lan, H. Zhao, J. Ma, J. Zhao, B. Xing, Nat. Water 2025, 3, 449.
|
| [48] |
L. Zhu, Y. Yang, F. Xu, X. Lu, M. Shuai, Z. An, X. Chen, H. Li, F. L. Martin, P. J. Vikesland, B. Ren, Z.-Q. Tian, Y.-G. Zhu, L. Cui, Sci. Adv. 2025, 11, eadp7991.
|
| [49] |
H.-K. Huang, H.-W. Cheng, C.-C. Liao, S.-J. Lin, Y.-Z. Chen, J.-K. Wang, Y.-L. Wang, N.-T. Huang, Lab Chip 2020, 20, 2520.
|
| [50] |
R. Hunter, A. N. Sohi, Z. Khatoon, V. R. Berthiaume, E. I. Alarcon, M. Godin, H. Anis, Sens. Actuators B Chem. 2019, 300, 126907.
|
| [51] |
K. S. Lee, F. C. Pereira, M. Palatinszky, L. Behrendt, U. Alcolombri, D. Berry, M. Wagner, R. Stocker, Nat. Protoc. 2021, 16, 634.
|
| [52] |
L. Shang, P. Liang, L. Xu, Y. Xue, K. Liu, Y. Wang, X. Bao, F. Chen, H. Peng, Y. Wang, J. Ju, B. Li, Anal. Chem. 2024, 96, 248.
|
| [53] |
P. Wen, F. Yang, H. Zhao, Y. Xu, S. Li, L. Chen, Anal. Chem. 2024, 96, 1454.
|
| [54] |
Z.-H. Fong, C.-H. Wang, C.-Y. Yang, H.-C. Kan, Y.-J. Lin, Y.-L. Chen, Y.-C. Shen, Y.-C. Yu, L.-K. Chau, C.-W. Io, S.-C. Wang, Microchem. J. 2025, 212, 113436.
|
| [55] |
S. Asgari, R. Dhital, A. Mustapha, M. Lin, Int. J. Food Microbiol. 2022, 383, 109947.
|
| [56] |
T. Lee, J. Lim, K. Park, E.-K. Lim, J.-J. Lee, ACS Sens. 2020, 5, 3099.
|
| [57] |
A. Boquet-Pujadas, T. Feaugas, A. Petracchini, A. Grassart, H. Mary, M. Manich, S. Gobaa, J.-C. Olivo-Marin, N. Sauvonnet, E. Labruyère, Sci. Adv. 2022, 8, eabo5767.
|
| [58] |
O. T. P. Nguyen, P. M. Misun, A. Hierlemann, C. Lohasz, Adv. Healthcare Mater. 2024, 13, 2302454.
|
| [59] |
J. M. Donkers, M. Wiese, T. J. Van Den Broek, E. Wierenga, V. Agamennone, F. Schuren and E. Van De Steeg, Microbiome Res. Rep. 2024, 3, 18.
|
| [60] |
J. Lee, N. Menon, C. T. Lim, Adv. Sci. 2024, 11, 2302113.
|
| [61] |
M. Ballerini, S. Galiè, P. Tyagi, C. Catozzi, H. Raji, A. Nabinejad, A. D. G. Macandog, A. Cordiale, B. I. Slivinschi, K. K. Kugiejko, M. Freisa, P. Occhetta, J. A. Wargo, P. F. Ferrucci, E. Cocorocchio, N. Segata, A. Vignati, A. Morgun, M. Deleidi, T. Manzo, M. Rasponi, L. Nezi, Nat. Biomed. Eng. 2025, 9, 967.
|
| [62] |
J. Wu, B. Zhang, X. Liu, W. Gu, F. Xu, J. Wang, Q. Liu, R. Wang, Y. Hu, J. Liu, X. Ji, H. Lv, X. Li, L. Peng, X. Li, Y. Zhang, S. Wang, Adv. Mater. 2024, 36, 2408485.
|
| [63] |
Y. Guo, R. Luo, Y. Wang, P. Deng, T. Song, M. Zhang, P. Wang, X. Zhang, K. Cui, T. Tao, Z. Li, W. Chen, Y. Zheng, J. Qin, Sci. Bull. 2021, 66, 783.
|
| [64] |
W. E. Lanik, C. J. Luke, L. S. Nolan, Q. Gong, L. C. Frazer, J. M. Rimer, S. E. Gale, R. Luc, S. S. Bidani, C. A. Sibbald, A. N. Lewis, B. Mihi, P. Agrawal, M. Goree, M. Maestas, E. Hu, D. G. Peters, M. Good, JCI Insight 2023, 8, e146496.
|
| [65] |
Y. Zhang, Y. Cai, X. Jin, Q. Wu, F. Bai, J. Liu, Nat. Chem. Biol. 2025, 21, 238.
|
| [66] |
L. Ma, J. Kim, R. Hatzenpichler, M. A. Karymov, N. Hubert, I. M. Hanan, E. B. Chang, R. F. Ismagilov, Proc. Natl. Acad. Sci. USA 2014, 111, 9768.
|
| [67] |
M. M. Villa, R. J. Bloom, J. D. Silverman, H. K. Durand, S. Jiang, A. Wu, E. P. Dallow, S. Huang, L. You, L. A. David, mSystems 2020, 5, e00864-19.
|
| [68] |
J. Yin, X. Chen, X. Li, G. Kang, P. Wang, Y. Song, U. Z. Ijaz, H. Yin, H. Huang, Front. Cell. Infect. Microbiol. 2022, 12, 920986.
|
| [69] |
L. M. Delong, C. E. Witt, M. Pennell, A. E. Ross, Lab Chip 2024, 24, 1918.
|
| [70] |
Y. Huang, R. U. Sheth, S. Zhao, L. A. Cohen, K. Dabaghi, T. Moody, Y. Sun, D. Ricaurte, M. Richardson, F. Velez-Cortes, T. Blazejewski, A. Kaufman, C. Ronda, H. H. Wang, Nat. Biotechnol. 2023, 41, 1424.
|
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