Abstract
Faecal (FM) and colon mucosal associated microbiota (MAM) were studied in a model of colorectal cancer (CRC), the Apc-mutated Pirc rats, and in age-paired wt F344 rats. Principal Coordinates Analysis indicated that samples’ distribution was driven by age, with samples of young rats (1 month old; without tumours) separated from older ones (11-month-old; bearing tumours). Diversity analysis showed significant differences between FM and MAM in older Pirc rats, and between MAM of both Pirc and wt rats and the tumour microbiota, enriched in Enterococcus, Escherichia/Shigella, Proteus and Bifidobacteriaceae. In young animals, Pirc FM was enriched in the genus Delftia, while wt FM was enriched in Lactobacillus and Streptococcus. Some CRC biomarkers and faecal short chain fatty acids (SCFAs) were also measured. Colon proliferation and DClK1 expression, a pro-survival mucosal marker, were higher in Pirc than in wt rats, while the mucin MUC2, was lower in Pirc rats. Branched SCFAs were higher in Pirc than in wt animals. By Spearman analysis CRC biomarkers correlated with FM (in both young and old rats) and with MAM (in young rats), suggesting a specific relationship between the gut microbiota profile and these functional mucosal parameters deserving further investigation.
Highlights
Faecal (FM) and colon mucosal associated microbiota (MAM) were studied in a model of colorectal cancer (CRC), the Apc-mutated Pirc rats, and in age-paired wt F344 rats
It has been shown that bacterial biofilms associated with the surface of colon epithelium are increased in a subset of sporadic CRC7 and in the apparently normal colon mucosa of patients with familial adenomatous polyposis (FAP), a genetic syndrome causing high risk of developing CRC5
Rank abundance curves analysis, showed the dominance of few bacterial OTUs in the tumour community compared with the normal mucosa (Fig. 1G,H); in particular the three bacterial OTUs dominating over the rest of the community correspond to Escherichia/Shigella, Streptococcus, and Bacteroides genera, in decreasing order of dominance and relative abundance, respectively
Summary
Faecal (FM) and colon mucosal associated microbiota (MAM) were studied in a model of colorectal cancer (CRC), the Apc-mutated Pirc rats, and in age-paired wt F344 rats. Ericsson et al documented that the faecal microbiota of Pirc rats and wt rats are s imilar[13] Given these contrasting results and the importance to characterize Pirc rats as a relevant model of CRC, we though it of interest to study the composition of their intestinal bacterial community in both the faeces and the colon mucosa. For this purpose, we compared the microbiota profiles of Pirc and wt rats at two different ages: 1 month-old, when the colon mucosa is morphologically normal with no macroscopic lesions[10], and in older rats (11-month-old), when colon tumours are present. Since Apc mutations have been reported to affect colon proliferation and cell survival[8], we studied PCNA expression, as a marker of proliferation, together with DClK1 expression, a microtubule-associated protein kinase regulating pro-survival s ignalling
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