Capturing one of the human gut microbiome's most wanted

Reconstructing the genome of a novel butyrate-producing, clostridial scavenger from metagenomic sequence data

Patricio Jeraldo, Alvaro Hernandez, Henrik B. Nielsen, Xianfeng Chen, Bryan A. White, Nigel Goldenfeld, Heidi Nelson, David Alhquist, Lisa Allyn Boardman, Nicholas D Chia

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble "most wanted" genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a "most wanted" taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.

Original languageEnglish (US)
Article number783
JournalFrontiers in Microbiology
Volume7
Issue numberMAY
DOIs
StatePublished - 2016

Fingerprint

Metagenomics
Butyrates
Microbiota
Genome
Bacteria
Anti-Inflammatory Agents
Eubacterium
Aptitude
Clostridium
Volatile Fatty Acids
Health
Vitamin B 12
Spores
Inflammatory Bowel Diseases
Methionine
Colonic Neoplasms
Genes
Virulence
Gastrointestinal Microbiome
Healthy Volunteers

Keywords

  • Binning
  • Butyricicoccus
  • Genome assembly
  • Metagenomics
  • Microbiome

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Capturing one of the human gut microbiome's most wanted : Reconstructing the genome of a novel butyrate-producing, clostridial scavenger from metagenomic sequence data. / Jeraldo, Patricio; Hernandez, Alvaro; Nielsen, Henrik B.; Chen, Xianfeng; White, Bryan A.; Goldenfeld, Nigel; Nelson, Heidi; Alhquist, David; Boardman, Lisa Allyn; Chia, Nicholas D.

In: Frontiers in Microbiology, Vol. 7, No. MAY, 783, 2016.

Research output: Contribution to journalArticle

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abstract = "The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of {"}most wanted{"} taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble {"}most wanted{"} genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a {"}most wanted{"} taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76{\%} average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.",
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