Difference between revisions of "Microbiome"

Revision as of 23:42, 20 July 2012

A microbiome is the totality of microbes, their genetic elements (genomes), and environmental interactions in a particular environment. The term "microbiome" was coined by Joshua Lederberg, who argued that microorganisms inhabiting the human body should be included as part of the human genome, because of their influence on human physiology. The human body contains over 10 times more microbial cells than human cells.^[1][2][3]

Microbiomes are being characterized in many other environments as well, including soil, seawater and freshwater systems.

Overview of human microbiome

• The human microbiome is a complex biological system — interactions between numerous genes and between the various species comprising the microbiome markedly affect its function, dynamics and impact on the host.

• Studying the human microbiome calls for a systems-based research and for system-level modeling, ultimately leading to a better and more profound understanding of the microbiome.

• Computational systems biology of in silico metabolic models proved extremely useful in studying microbial metabolism.

• Two fundamentally different approaches can be used to model microbiome metabolism: genome-based multi-species models and metagenomics-based supra-organism models.

• Preliminary studies of these modeling approaches demonstrate tremendous potential but several challenges should be addressed before a comprehensive modeling framework can be

introduced.

Human microbiome composition

Anatomic regions of the gut

• Over 100 trillion organisms (10_14</sup>)
• 100 fold more genes in our gut then in us

• Upper GI tract: 102 – 104 cells/ml
  • Lactobacilli, streptococci, H pylori
• Ileum: 106-1012 cells /ml, upper bacteria plus
  • Faculative anaerobes: Enterobacteriaceae
  • Obligate anaerobes: Bacteroides, Veillonella, Fusobacterium, and Clostridium species
• Colon: distal human colon is the most biodense natural ecosystem known (1010-1012 cells/ml)
  • Complex and diverse
  • Comprise most of our bacterial biomass

• Firmicutes, bacteroidetes, actinobacteria, proteobacteria, and others.

Gut flora and metabolism

Source: Hooper, et al. Annu Rev Nutr, 2002.

• Microbial genomes enhance our metabolic activity
• May indirectly or directly effect our metabolism
• The colon is very active metabolically
  • 20-70 gms of carbos and 5-20 gms of protein/day
  • Over 100 kcal per day!
• Mass of colonic microbiome = single kidney
• Metabolically as active as the liver

• Energy salvage: esp via the short-chain fatty acids
  • Acetate, butyrate, propionate (SCFAs)
  • Absorbed into body and used by liver and others organs
  • Acetate and propionate modulate glucose metabolism in the liver and adipocytes (glycemic index)
  • 50-70% of colonic cell energy derived from butyrate

• Mice and humans have different gut flora but the two largest divisions are shared in common:
  • Bacteroidetes (Gram -)
  • Firmicutes (Gram +)

  These flora change in response to diet and obesity of host

Regulators

• Archae: 1-2 % of mouse and human flora
• Represent a major microbial group in gut flora Increased in obese mice
• Many are methanogenic : Methanobacter smithii
• Converts CO2 and H2 gas to methane
• By decreasing the partial pressure of H2 gas these bacteria can drive bacterial metabolism
• The flora of obese mice are more efficient at extracting energy: "The Energy Harvest".

Research questions

Systems biology research has already revolutionized genomics and could similarly transform metagenomic research and particularly research of the human microbiome.

Systems based research represents a unique opportunity for addressing several of the most pressing questions concerning the human microbiome:

• What determines the assembly of the microbiome and what role do interspecific interactions play in its composition?
• Which factors govern the response of the microbiome to various perturbations?
• How does the microbiome, as a whole, interact with the human host and how does it impact human health?

Online resources for the human microbiome

The following are a list of useful online resources for systems biology and modeling of the human microbiome:

• Microbial genomic data and analysis
  • IMG
  • DACC
  • GOLD
  • Microbes online
  • RAST
• Metagenomic data and analysis
  • IMG/M
  • MG-RAST
  • METAREP
• Metabolic databases
  • KEGG
  • MetaCyc
  • Brenda
• Metabolic model reconstruction, visualization, and analysis
  • The Model Seed
  • Systems Biology Research Group
  • iPath
  • Pathway Tools
  • Cytoscape
  • Cobra
• Reverse ecology software
  • NetSeed

See also

• KEGG
• MetaCyc

Concepts

• wikipedia:Directed graph
• flux balance analysis (FBA)

Glossary

metatran-scriptomic

meta-metabolomic

auxotrophy 

(Gr. αὐξάνω "to increase"; τροφή "nourishment") is most commonly defined as the inability of an organism to synthesize a particular organic compound required for its growth (as defined by IUPAC). An auxotroph is an organism that displays this characteristic; auxotrophic is the corresponding adjective.

bacteriotherapy 

the modulation of one's microbiota via antibiotics and probiotics or the transplantation of a complete microbiota into a recipient. (see: Clostridium difficile)

ecosystomics 

a high-throughput systematic study of all realizable ecosystems in a given environment.

Keywords

systems biology; metabolic models; human microbiome; metagenomics; reverse ecology; ecosystomics

References

1. ↑ Zimmer, Carl (13 July 2010). "How Microbes Defend and Define Us". New York Times.
2. ↑ Because bacteria are 10-100 times smaller than human cells, the entire microbiome weighs about 200 grams.
3. ↑ Coyle WJ. "The Human Microbiome: The Undiscovered Country".

External links

• wikipedia:Human Microbiome Project