A research paper in this week's Nature shows a major advance in the study of the role of the human gut flora in disease and health. Metagenomics of the Human Intestinal Tract (MetaHIT) Consortium examined the role of gut flora in health by a massive project (ref. below) to determine the DNA base sequence of the majority of the millions of genes in the thousands of species of bacteria that abide in human feces. Gut flora have been linked to many human diseases, as well as the normal function of the human immune system.
Major Findings:
- 576.7 gigabases sequenced (150 times larger than human genome)
- Identified 3.3 million gut flora genes
- Represents more than 1,000 bacterial species
- Each individual harbors approx. 160 different species
- Most prevalent species are identified and shared by everyone
Feces from 124 Europeans
Feces samples (124 individuals total) from a Danish project to determine the role of gut flora in obesity and from a Spanish project to determine the role of gut flora in Crohn’s disease and ulcerative colitis, were extracted for total DNA.
Illumina Multiplex Sequencing of PCR Amplified Fragments
DNA samples from each individual were fragments (<800 bp) and amplified to include indexing information and sequencing primers. The sequences of a dozen of the fragments at a time was determined using a dozen different dyes (Illumina multiplexing). Sample preparation and analysis was fully automated to permit identification of overlapping contiguous sequences and assembly of bacterial genomes (1,000-1,150 most common). The sequence data in this study represents most of the bacterial species of the gut.
Comparison to 89 Existing Human Gut Bacteria Genome Sequences
The new study represented more than 200 times the sequence information than in all previous studies combined. Existing genome sequences could be identified among the bacterial genomes assembled from the new data. The identified and sequenced bacterial species represent approximately a tenth of the common bacteria in the gut.
Polysaccharide/sugar Metabolism Common among Gut Flora
Genes coding for enzymes needed to metabolize pectin, sorbitol, mannose, fructose, cellulose and sucrose, were common among the gut flora. Bacteriophages were also significantly (5%) represented in the total gut metagenome. Most of the genes were assigned recognizable bacterial functions, but many genes, presumably involved in interactions among the bacterial community or in modification of gut function have not been characterized.
Obese, Crohn’s Disease, Ulcerative Colitis, Compared to Healthy
The bacterial gene compostion of individuals diagnosed with Crohn’s Disease and ulcerative colitis were different and distinct from healthy individuals. Individuals with Crohn’s disease had 25% fewer species of gut flora than comparable healthy controls.
This study demonstrates the feasibility of using current techniques to examine in detail the interactions between gut flora and tissues of the gut that are involved in health and disease. This also suggests the risks of antibiotics in altering critical functions of the gut flora, as well as the alteration of gut flora to support health and cure disease.
reference:
Junjie Qin, et al. 2010. A human gut microbial gene catalogue
established by metagenomic sequencing. Nature 464, 59-65.
