Abstract
Caerulomycin A (CRM A) is the first example of natural caerulomycins with a 2,2′-bipyridyl ring core and 6-aldoxime functional group from Streptomyces caeruleus and recently from marine-derived Actinoalloteichus cyanogriseus WH1-2216-6. Our previous study revealed that CRM A showed anti-tumor activity against human colorectal cancer (CRC) both in vitro and in vivo. Because some intestinal flora can affect the occurrence and development of CRC, the influence of CRM A on the intestinal flora is worthy of study in Sprague–Dawley (SD) rats. The high throughput sequencing of the V3-V4 hypervariable region in bacterial 16S rDNA gene results showed that the CRM A affected the diversity of intestinal flora of the SD rats treated with CRM A for 2, 3 and 4 weeks. Further analysis indicated that the abundance of genera Prevotella_1, Prevotellaceae_UCG-001, and Lactobacillus were increased while the that of genera Alloprevotella and Ruminiclostridium_1 were decreased. For the CRC related intestinal flora, the abundance of genera Bacteroides, Fusobacterium, Enterococcus, Escherichia-Shigella, Klebsiella, Streptococcus, Ruminococcus_2, and Peptococcus of SD rats treated with CRM A were decreased, while that of abundance of genera Bifidobacterium, Lactobacillus, Faecalibacterium, Blautia, Oscillibacter, and Clostridium were increased. The results indicated that CRM A could influence the intestinal flora by inhibiting some species of harmful flora and improving the beneficial bacteria in intestinal flora in the SD rats. The results may provide a new idea for revealing the mechanism of the anti-CRC activity of CRM A.
Highlights
Caerulomycin A (CRM A) is a member of natural products containing a 2,20 -bipyridyl core structure, first isolated from the Streptomyces caeruleus by Funk and Divei in 1959 [1]
Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, Streptococcus gallolyticus, and Enterococcus faecalis have been shown to promote the development of colorectal cancer (CRC) while Bifidobacterium, Lactobacillus, Faecalibacterium, Blautia, Oscillibacter, and Clostridium are negatively associated with CRC [18,19,20,21,22]
The influence of CRM A on the intestinal flora of SD rats was investigated by administration for different numbers of days
Summary
Caerulomycin A (CRM A) is a member of natural products containing a 2,20 -bipyridyl core structure, first isolated from the Streptomyces caeruleus by Funk and Divei in 1959 [1]. We isolated it from the marine-derived Actinoalloteichus cyanogriseus WH1-2216-6 in 2011 [2] and demonstrated its biosynthesis pathway in the later cooperative research [3,4,5,6], which afforded the possibility for large yield and druggability study of CRM A. More and more evidence indicates that the occurrence and development of CRC is closely related to the imbalance of human intestinal microbiota.
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