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Should we target the microbiota in the treatment of colorectal cancer?
Bullman S, Pedamallu C, Sicinska E, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017. pii: eaal5240. doi: 10.1126/science.aal5240. [Epub ahead of print 23 Nov 2017].
The gut microbiota has emerged as a key driver of colorectal cancer (CRC) development and progression. Several recent studies have shown that higher levels of Fusobacterium species are present in human CRC tissue compared with adjacent normal mucosa. Fusobacteria can protect the tumour through suppression of immunity and tumour cell killing, leading to the suggestion that Fusobacteria may actually promote tumour growth and survival. This recent study investigated the role of Fusobacterium and its associated microbiome in CRC. Analysing five independent patient cohorts, they demonstrated that the microbiota associated with Fusobacterium-positive CRC was also seen in distal metastases, reported as microbiota similarity between paired primary–metastatic tumours, which was not seen to exist in Fusobacterium-negative patient samples. Locational analysis indicated that Fusobacterium was associated with cancer cells within the metastatic lesions, and the authors hypothesised that the bacteria travelled with the primary tumour cells to metastatic sites. To look at whether viable Fusobacterium could persist in transfer experiments, xenografts from CRC tissue were implanted subcutaneously into Nu/Nu mice, and the authors were able to recover viable Fusobacterium and a number of co-occurring microbes through successive passages. Finally, the researchers interrogated the impact of antibiotic treatment on colon cancer xenografts and demonstrated that metronidazole treatment decreased Fusobacterium load while simultaneously reducing cancer cell proliferation and causing a reduction in tumour size. The study further highlights the role of the gut microbiota in the pathogenesis of CRC and potentially its treatment.
The role of MMP-7 in biliary atresia
Lertudomphonwanit C, Mourya R, Fei L, et al. Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia. Science Translational Medicine 2017;(417). DOI: …
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