Date Published: May 31, 2018
Publisher: Public Library of Science
Author(s): Kristin Marie Valand Herstad, Aina Elisabeth Fossum Moen, John Christian Gaby, Lars Moe, Ellen Skancke, Mathias Chamaillard.
Colorectal epithelial tumors occur spontaneously in dogs, and the pathogenesis seems to parallel that of humans. The development of human colorectal tumorigenesis has been linked to alterations in the composition of the intestinal microbiota. This study characterized the fecal- and mucosa-associated microbiota in dogs with colorectal epithelial tumors (n = 10). The fecal microbiota was characterized by 16S rDNA analysis and compared with that of control dogs (n = 13). We also determined the mucosa-associated microbiota composition in colonic tumor tissue (n = 8) and in adjacent non-tumor tissue (n = 5) by 16S rDNA- and rRNA profiling. The fecal microbial community structure in dogs with tumors was different from that of control samples and was distinguished by oligotypes affiliated with Enterobacteriaceae, Bacteroides, Helicobacter, Porphyromonas, Peptostreptococcus and Streptococcus, and lower abundance of Ruminococcaceae, Slackia, Clostridium XI and Faecalibacterium. The overall community structure and populations of mucosal bacteria were not different based on either the 16S rDNA or the 16S rRNA profile in tumor tissue vs. adjacent non-tumor tissue. However, the proportion of live, potentially active bacteria appeared to be higher in non-tumor tissue compared with tumor tissue and included Slackia, Roseburia, unclass. Ruminococcaeceae, unclass. Lachnospiraceae and Oscillibacter. Colorectal tumors are rarely diagnosed in dogs, but despite this limitation, we were able to show that dogs with colorectal tumors have distinct fecal microbiota profiles. These initial results support the need for future case-control studies that are adequately powered, as well as age-matched and breed-matched, in order to evaluate the influence of bacteria on colorectal cancer etiopathogenesis and to determine whether the bacteria may have potential as biomarkers in clinical settings.
In dogs colorectal epithelial tumors occur spontaneously, and similarly to humans, adenocarcinoma is one of the most common malignant tumors. Sporadic colorectal adenocarcinoma in humans often arises from benign polyps that develop into adenomas, and it involves multiple steps of genetic and epigenetic alterations . This same developmental process is also thought to occur in dogs [2–5]. In humans, genetic predisposition, diet, environment and intestinal bacteria are implicated in the etiopathogenesis [6–10]. Intestinal bacteria with pro-carcinogenic properties, such as Helicobacter pylori, Escherichia coli, Streptococcus gallolyticus (formerly bovis), Fusobacterium spp., and Bacteroides fragiles have been identified in fecal or tumor samples from human patients with adenoma and carcinoma [11–15]. Presence of potentially pathogenic bacteria and/or bacterial dysbiosis is commonly observed in these patients [16, 17]. Current evidence suggests that rather than only one pathogenic microbe, a complex network of microbes is involved in the pathogenesis of disease [17, 18].
The study protocol was reviewed and approved according to the guidelines of the ethics committee at the Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU) (approval number: 14/04723). Written informed consent was given by all dog-owners before participation, and they were informed that their participation in the study was voluntary.
The intestinal microbiota, dominated by bacteria, is believed to have a major influence on host health and wellbeing . Dysbiosis, an unhealthy disruption in the intestinal bacterial community, has been described in humans with early and late stages of colorectal cancer [55, 56]. Although colorectal cancer in dogs is rare, and therefore less characterized as compared to humans, studies have suggested similarities in the etiopathogenesis in these species [57, 58]. To our knowledge, this is the first study to give detailed insight into both the fecal- and mucosa-associated microbiota in dogs diagnosed with colorectal polyps, adenomas and carcinomas.
The fecal microbiota composition in dogs with colorectal epithelial tumors was different from that of control dogs and consisted of low-abundance but potentially pathogenic bacteria as well a reduction of possible health-promoting bacteria within Clostridiales. The mucosa-associated microbiota composition was not restricted to tumor tissue but was also present in adjacent non-tumor tissue, indicating that the microbiota was unlikely to have resulted from localized tumor changes, such as inflammation and ulcerations. Our results provide knowledge which might be helpful for future research into the etiopathogenesis of canine colorectal tumorigenesis as well for the development of bacterial biomarkers to screen for the disease.