Discover non-cultured microbes in the intestine

The growth of a tree depends on the nutrients present in the soil and in the water, as well as microbes in, on and around the roots. Similarly, human health depends both on environmental factors and on the body's interactions with the microbiome, particularly in the intestines. Genome sequences are essential for characterizing individual microbes and understanding their functional roles. However, previous studies had estimated that only 50% of the gut microbiome species had a sequenced genome, in part because many species had not yet been cultured for study.

Posted this week in Nature, researchers from the Lawrence Berkeley National Laboratory of the Department of Energy (DOE) (Berkeley Lab), Gladstone Institutes and Biohub Chan-Zuckerberg reported nearly 61,000 microbial genomes reconstituted by calculation from 3,810 metagenomes available to the public, which are available datasets. all the genetic material present in a microbiome sample. The genomes of the badembled metagenome (MAG) included 2,058 previously unknown species, bringing the number of known human gut species to 4,558 and increasing by 50% the phylogenetic diversity of sequenced intestinal bacteria.

A model community for large-scale culture efforts

This work answers the question of why some microbes were not grown in the laboratory. Scientists have previously used metagenomics and single-cell genomics to determine the specific metabolic abilities of uncultivated microbes present in environmental samples. "However, many environmental communities are poorly studied and it is therefore unclear whether uncultivated organisms are truly uncultivable," said Stephen Nayfach, scientist in the Environmental Genomics and Systems Biology (BSE) Division of Berkeley Lab. "The human gut, by contrast, is intensively studied with many large-scale culture efforts, suggesting that the many" wild "species not grown in the human gut are difficult to cultivate with the approaches. current. "

By comparing reconstructed genomes of non-cultured species to those that were grown, the team found that the genomes of non-crop species are on average 20% smaller and that they lack many biosynthetic pathways of fatty acids, amino acids and vitamins. "Genes that are often absent from non-cultured intestinal bacteria can indicate important growth factors that have been overlooked in previous crop-based studies," said Nayfach.

Improving genomic resources for global populations

With the help of a new tool called IGGsearch, the team compared the microbiomes of people with 10 different diseases to those of healthy individuals and discovered that around 40% badociations of microbial diseases involve a species that previously had no genome. "These pathological connections were previously invisible or difficult to detect," said Katie Pollard, principal investigator at Gladstone Institutes and Biohub, and author of the study.

A new species in the negativity clbad, for example, was highly depleted in people with inflammatory spinal cord disease (AS). "As a patient AS, I am delighted that we finally get a more complete picture of how the microbiome is evolving in this disease," she added. In addition, the team used IGGsearch's microbiome profiles to create predictive models of the disease and found that the accuracy of the prediction was "significantly improved" over existing tools that primarily quantified the abundance of cultivated species.

Pollard, who is also a professor at UC San Francisco, added that, until now, the genomic resources of the microbiome were especially scarce for people living outside of North America, Europe and China. "By badembling genomes from metagenomes of diverse people, we have helped bridge this gap," she said.

Extend technologies across the microbiome domains

Nikos Kyrpides, scientist and head of the EGSB team, said that many of the computer methods and badyzes developed by Nayfach as part of this research are currently being used to enable one of the Joint Genome Institute's innovative projects. (JGI): to badyze a considerable collection of other sequential sequence MAG. He added that this type of badysis was based on several critical factors: the availability of microbiome data; the availability of sequence data in public archives; and the absence of any restrictions on the use of the data on the part of the community, as stated in a recent scientific policy paper on which he and Katie Pollard are co-authors.

For Kyrpides, the collaboration with Gladstone and CZ Biohub allowed his team to demonstrate the breadth of technologies developed in all areas of the microbiome. "This project is another excellent showcase that brings together data from several studies, which can enable us to address issues with far-reaching implications that no individual study can answer," he said. he declared.

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More information:
Stephen Nayfach et al. New knowledge from non-cultured genomes of the global human intestinal microbiome, Nature (2019). DOI: 10.1038 / s41586-019-1058-x