Right-sided colonic biofilms are associated with adenoma formation in patients with Lynch syndrome.

Colonic bacterial biofilms are an emerging manifestation in colorectal cancer (CRC); they exhibit carcinogenic properties and are frequently present on right-sided cancerous lesions. Whether bacterial biofilms propose a risk factor for early carcinogenesis in humans is yet unresolved. Therefore, we studied bacterial biofilms in tandem with adenoma formation in patients with Lynch syndrome (LS). LS patients carry a pathogenic germline variant in one of the DNA mismatch repair (MMR) genes, resulting in a variable predisposition to develop colonic cancerous lesions. A total of 100 LS patients were included in our study, consisting of 23 MLH1, 24 MSH2, 36 MSH6, and 17 PMS2 MMR variants. During regular screening colonoscopies, normal-appearing forceps biopsies were taken from colon ascendens (right colon) and descendens (left colon). Biopsies were screened for bacterial biofilms using fluorescent in situ hybridization by targeting bacterial 16s rRNA. The frequency of colorectal adenomas (tubular adenomas and [tubulo]villous adenomas) before and during colonoscopy was registered. Overall, 60% of patients presented with a biofilm, of which most were right-sided (right-sided: 25%, both sides: 21%, left-sided: 14%). Interestingly, adenomas were more frequently present in patients with a right-sided biofilm (right-sided: 64%, both sides: 58%) than in patients with a left-sided biofilm (29%) or no biofilm (38%). The occurrence of bacterial biofilms was not correlated with age, BMI, or MMR-variant. Statistical analysis revealed that right-sided bacterial biofilms correlated with right-sided adenomas (Pearson: 0.272, p=0.007) and left-sided adenomas (Pearson: 0.227, p=0.026), while left-sided biofilms were not correlated with left- or right-sided adenomas (Pearson: 0.037, p=0.718 and -.127, p=.213). To model the probability of right-sided adenoma formation, we performed a binary logistic regression analysis and found that age (odds ratio: 1.065 [CI: 1.024; 1.108, p=0.002]) and right-sided biofilms (odds ratio: 3.020 [CI: 1.151; 7.926, p=0.025]) significantly contributed. Our data suggest that right-sided bacterial biofilms are a hallmark for high-risk LS patients and may play a role in early carcinogenesis. This abstract is also being presented as Poster A06. Citation Format: Carlijn Bruggeling, Vera Witjes, Daniel Garza, Milou Fransen, Joyce Krekels, Tanya Bisseling, Mariette van Kouwen, Nicoline Hoogerbrugge, Sebastian Lucker, Bas Dutilh, Iris Nagtegaal, Annemarie Boleij. Right-sided colonic biofilms are associated with adenoma formation in patients with Lynch syndrome [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr PR01.