MICROBIOME

Culturing the human microbiota and culturomics

Abstract

The gut microbiota has an important role in the maintenance of human health and in disease pathogenesis. This importance was realized through the advent of omics technologies and their application to improve our knowledge of the gut microbial ecosystem. In particular, the use of metagenomics has revealed the diversity of the gut microbiota, but it has also highlighted that the majority of bacteria in the gut remain uncultured. Culturomics was developed to culture and identify unknown bacteria that inhabit the human gut as a part of the rebirth of culture techniques in microbiology. Consisting of multiple culture conditions combined with the rapid identification of bacteria, the culturomic approach has enabled the culture of hundreds of new microorganisms that are associated with humans, providing exciting new perspectives on host–bacteria relationships. In this Review, we discuss why and how culturomics was developed. We describe how culturomics has extended our understanding of bacterial diversity and then explore how culturomics can be applied to the study of the human microbiota and the potential implications for human health.

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Fig. 1: The strengths and weaknesses of metagenomic studies.
Fig. 2: The culturomic workflow.
Fig. 3: The history and future potential applications of culturomics in clinical microbiology.

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Acknowledgements

This work has benefited from French State support, managed by the ‘Agence Nationale pour la Recherche’, including the ‘Programme d’Investissement d’Avenir’ under the reference Méditerranée Infection 10-IAHU-03. This work was also funded by the Prix Louis D. and by Région Provence Alpes Côte d’Azur and European funding FEDER PRIMI.

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J.-C.L., G.D., M.M., F.C., M.B., F.F., A.L. and D.R. researched the data for the article. J.-C.L., G.D., M.M., J.-M.R., P.-E.F. and D.R. substantially contributed to discussion of content. J.-C.L., G.D., M.M., F.C., M.B., F.F., A.L., P.-E.F. and D.R. wrote the article. J.-C.L., G.D., M.M., F.C., M.B., F.F., A.L., J.-M.R., P.-E.F. and D.R. reviewed and edited the manuscript before submission.

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Correspondence to Didier Raoult.

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Glossary

Microbiota

Consortia of microorganisms living in a defined environment.

Commensal

Microorganism that colonizes its host without causing disease.

Probiotics

Living microorganisms that can be beneficial for health.

Metagenomics

Shotgun sequencing of DNA isolated directly from a specific environment.

Bacteriotherapy

Administration of live microorganisms, alone or as complete ecosystems, to improve human health. FMT is an example of bacteriotherapy.

Microbial dark matter

Unassigned sequences from metagenomic studies.

MALDI-TOF mass spectrometry

Combination of a soft ionization method (MALDI) with mass spectrometry, enabling the identification of proteins through their mass and their charge number.

Diffusion chamber

A method that allows microorganisms to grow in their natural environment, the inoculum being sandwiched between semipermeable membranes of the chamber, allowing a free exchange of chemicals with the external milieu.

Obligate anaerobes

Organisms for which atmospheric oxygen concentration is toxic.

Shell-vial technique

A centrifuge-enhanced tissue culture assay.

Axenic media

Host-cell-free growth culture media.

Anaerobes

Organisms that do not require oxygen for growth.

Schaedler agar

Solid culture medium recommended for the isolation of anaerobic bacteria from clinical specimens.

Xylanolytic microbial communities

Communities containing prokaryotes with the ability to degrade xylan.

Taxonogenomics

Modern approach to describe new taxa isolated from culturomic studies combining genome sequencing and phenotypic information.

Operational taxonomic units.

Clusters of DNA sequences from unidentified organisms organized according to their DNA sequence similarity.

Microbiome

All genes and genomes of a microbiota.

Kwashiorkor

Clinical nutritional disease including irritability, diarrhoea with indigested food, swelling of the hands and feet (nutritional oedema), general puffiness of the face (moon face) and skin changes (depigmentation and thickened black and crumpled patches with peeling and rash).

Faecal microbiota transplantation

The transfer of faecal material from a healthy individual into an individual with a condition.

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Lagier, J., Dubourg, G., Million, M. et al. Culturing the human microbiota and culturomics. Nat Rev Microbiol 16, 540–550 (2018). https://doi.org/10.1038/s41579-018-0041-0

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