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  • Perspective
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Enabling next-generation anaerobic cultivation through biotechnology to advance functional microbiome research

Abstract

Microbiomes are complex communities of microorganisms that are essential for biochemical processes on Earth and for the health of humans, animals and plants. Many environmental and host-associated microbiomes are dominated by anaerobic microbes, some of which cannot tolerate oxygen. Anaerobic microbial communities have been extensively studied over the last 20 years using molecular techniques, especially next-generation sequencing. However, there is a renewed interest in microbial cultivation because isolates provide the basis for understanding the taxonomic and functional units of biodiversity, elucidating novel biochemical pathways and the mechanisms underlying microbe–microbe and microbe–host interactions and opening new avenues for biotechnological and clinical applications. In this Perspective, we present areas of research and applications that will benefit from advancement in anaerobic microbial cultivation. We highlight key technical and infrastructural hurdles associated with the development and deployment of sophisticated cultivation workflows. Improving the performance of cultivation techniques will set new trends in functional microbiome research in the coming years.

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Fig. 1: Schematic illustration of the transition from current anaerobic cultivation methods (bottom) to next-generation anaerobic cultivation methods (top).
Fig. 2: Schematic of a potential high-throughput anaerobic cultivation unit and main design considerations.

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Acknowledgements

We thank S. Nüchtern (Functional Microbiome Research Group, Institute of Medical Microbiology, RWTH University Hospital) for outside support with high-throughput anaerobic cultivation, which contributed to some of the ideas in this manuscript. T.C. received funding from the German Research Foundation (DFG; 403224013 ‘SFB1382’, 445552570 and 513892404). T.C. and D.H. received funding from the German Ministry for Research and Education (BMBF; project Mi-EOCRC (K.Z. 01KD2102D)). T.C., D.H. and B.S. received funding from the DFG (395357507 ‘SFB1371’). B.S. received additional funding from the European Research Council (ERC; EvoGutHealth, 865615) and the Germany Centre for Infection Research (DZIF; 503-5-7-06.712_00 and 503-5-7-06.709_00). T.C. and J.O. received funding from the DFG (6270054 NFDI 28/1 ‘NFDI4Microbiota’). J.O. received additional funding from the DFG (6270048 NFDI 5/1 ‘NFDI4Biodiversity’), the BMBF (8005512901 and 8005512001 of DZIF) and EU/Horizon IRA (MICROBE no. 101094353). L.M. received funding from the DFG (EXC2124, MA 8164/1-2) and the ERC (gutMAP, 101076967). A.T. received funding from the ERC (uCARE, 819454). F.F. and A.J.W. received funding from the DFG (SFB ‘DECIDE’ 1583/1, 492620490). A.J.W. received additional funding from the ERC (GUT-CHECK, 101040214).

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Clavel, T., Faber, F., Groussin, M. et al. Enabling next-generation anaerobic cultivation through biotechnology to advance functional microbiome research. Nat Biotechnol 43, 878–888 (2025). https://doi.org/10.1038/s41587-025-02660-6

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