Thursday, December 1, 2011

Research news - Fusobacterium and colon cancer

Two recent papers (Castellarin et al and Kostic et al) have come out in Genome Research showing an association between bacteria of the genus Fusobacterium and colon carcinoma. This is of interest to oral microbiologists as Fusobacterium, especially the species F. nucleatum, is one of the most common bugs in the mouth, but is not particularly prevalent in the gut normally.
Both groups took somewhat similar approaches. Castellarin and co-workers used Illumina deep sequencing of cDNA from tumors compared to control samples from the same patients, while Kostic and co-workers did similar sequencing of genomic DNA. In either case they subtracted human sequences and looked for the remaining sequences that were similar to bacterial DNA. This was doubtless made easier by the extensive sequencing of bacterial genomes that has been done by the Human Microbiome Project. In both studies, the sequences that were most overrepresented in tumors mapped to Fusobacterium. Both sets of workers confirmed their findings by looking at larger patient groups. Castellarin et al did this by qPCR with Fusobacterium specific primers, while Kostic used pyrosequencing of 16S rRNA genes.
Kostic et al demonstrated the presence of the bacteria in tumors by FISH, while Castellarin et al was able to grow a single culture of the bacterium from a frozen tumor, and then sequenced the genome. The organism they cultured was relatively similar to a cultured un-named strain called Fusobacterium sp. 3_1_36A2. They further showed that their cultured bacterium would invade Caco-2 colon carcinoma cells in culture. Fusobacterium has been known to be invasive to human cells in the mouth and in culture for a while, so this is not totally unexpected.
Overall, this is an intriguing finding, and of course 2 labs publishing at the same time shows it must be real. Its not clear yet whether the presence of the bacteria is causing the tumors, though. It may just be preferentially infecting the tumor cells. Helicobacter pylori is thought to contribute to stomach cancer by stimulating inflammation and it is possible that Fusobacterium does something similar in the gut. In our studies, we have not seen a clear relationship between Fusobacterium and the inflammatory disease chronic periodontitis, but perhaps it is a gut-specific phenomenon. The availability of the cultured organism is exciting, suggesting that animal models might be possible.

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