Abstract 472P
Background
Although the gut microbiome has been linked with colorectal cancer (CRC), there is limited data on the significance of the microbiome in various subtypes of CRC such as proximal versus distal CRC and young-onset CRC. Also, fecal sample collection is a major hurdle in microbiome studies. This study evaluates the utility of anal swabs collected during clinic visits as an alternative for gut microbiome profiling and examines its relationship with tumor location and age at diagnosis.
Methods
Anal swabs were obtained from 86 enrolled patients (of 100 planned) with advanced colorectal cancer. Of these, 68 samples have been sequenced and 65 remained for analysis after quality filtering. Relevant clinical parameters are shown in Table. Fecal samples were obtained from 10 of these patients to compare with their anal swabs. Bacterial microbiomes were profiled using the V3-V4 region of 16S rRNA and compared by body site, primary tumor location, and age at diagnosis.
Results
Community diversity analyses of fecal samples and paired anal samples were similar. Anal samples demonstrated a high abundance and diversity of several gut bacteria including Clostridia and Prevotellaceae, along with increased relative abundance of skin commensals such as Corynebacteria and Staphylococcaceae compared with fecal samples. The anal microbiome of young-onset CRC patients had decreased relative abundance of Fusobacteria compared to onset ≥50 (Table). Proximal CRC showed higher relative abundance of Bacteroidetes and lower Clostridia compared with distal cancers (Table). Table: 472P
| Enriched Taxa (p-value) | ||||
| Phylum | Class | Family | Genus | |
| Primary Tumor Location | ||||
| Proximal (n=23) | Bacteroidetes (4e-3) | Negativicutes (2e-3) | Porphyromonadaceae (0.01), Prevotellaceae (0.01) | Prevotella (0.02), Porphyromonas (0.02) |
| Distal (n=42) | Actinobacteria (8e-3) | Clostridia (8e-3) | Clostridiaceae (0.02) | |
| Diagnosis Age | ||||
| Diagnosed <50 years old (n=23) | ||||
| Diagnosed ≥50 years old (n=42) | Fusobacteria (0.03) | Fusobacteriia (0.04) |
Conclusions
This pilot study demonstrates the utility of anal swabs as an alternative to stool samples in human studies where accrual is limited due to issues obtaining stool samples. Our study demonstrated distinct anal microbiomes between proximal versus distal CRC and young versus late (≥50) onset CRC. Future studies examining the anal microbiome in CRC could help harness the potential of the microbiome in management of this disease.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Grants and discretionary funds of author PMK from Division of Internal Medicine and Center of Advancement, Holden Comprehensive Cancer Center. Grants of author AKM from the Schwab Foundation Margaret Heppelmann and Michael Wacek, NIH R01 grant, and VA Merit Award SA was supported by the Emory Warner Medical Student Research Fellowship.
Disclosure
P.M. Kasi: Non-Financial Interests, Personal, Advisory Board: Foundation Medicine; Natera Oncology; AstraZeneca; Merck MSD; Financial Interests, Institutional, Advisory Board, Investigator initiated trial cooperative group PI trial support and funding: Tersera; Financial Interests, Institutional, Advisory Board, Investigator initiated trial trial support and funding: Boston Scientific. A.K. Mangalam: Financial Interests, Institutional, Royalties: Mayo Clinic (Evelo Biosciences). All other authors have declared no conflicts of interest.