Microbial culturomics: paradigm shift in the human gut microbiome study.

Area of Science:

• Microbiology
• Human Gut Microbiome
• Metagenomics

Background:

• Understanding the gut microbiota's composition and its link to health and disease is a significant scientific challenge.
• Metagenomic analysis often fails to detect uncultured bacteria, limiting comprehensive microbiome characterization.

Purpose of the Study:

• To comprehensively determine the microbial composition of the human gut microbiota using microbial culturomics.
• To compare culturomics with metagenomic analysis for a more complete understanding of the gut microbiome.

Main Methods:

• Studied stool samples from two lean Africans and one obese European.
• Employed 212 different culture conditions (microbial culturomics) followed by mass spectrometry and 16S rRNA sequencing.
• Performed parallel metagenomic analysis using 16S rRNA amplicon pyrosequencing (V6 region).

Main Results:

• Culturomics yielded 340 bacterial species, including novel species from rare phyla, five fungi, and a giant virus (Senegalvirus).
• 174 species identified by culturomics were previously undescribed in the human gut, with 31 new species and genera.
• Generated approximately 10,000 new unknown genes (ORFans) and identified the largest bacterial genome (Microvirga massiliensis) and largest gut virus (Senegalvirus) reported.
• Metagenomic analysis identified 698 phylotypes, with 51 overlapping with culturomics findings.
• Culturomics identified species missed by metagenomics, overcoming depth bias.

Conclusions:

• Microbial culturomics significantly complements metagenomics in characterizing the human gut microbiome.
• This study expands the known diversity of the human gut microbiome, providing new genetic resources for future research.
• The findings highlight the importance of culturomics for discovering novel microorganisms and their potential roles in health and disease.