Microbiota Profile and Impact of Fusobacterium nucleatum in Colorectal Cancer Patients of Barretos Cancer Hospital

Microbial diversity has been pointed out as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of <i>Fusobacterium nucleatum</i> (<i>Fn</i>) DNA in CRC prognosis was further evaluated by qPCR in a series of 152 CRC cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with <i>Fusobacterium</i> being the most abundant genus in the tumor tissue. In the validation dataset, <i>Fn</i> was detected in 35/152 (23.0%) of fresh-frozen tumor samples and in 6/57 (10.5%) of paired normal adjacent tissue, with higher levels in the tumor (<i>p</i> = 0.0033). <i>Fn</i> DNA in the tumor tissue was significantly associated with proximal tumors (<i>p</i> = 0.001), higher depth of invasion (<i>p</i> = 0.014), higher clinical stages (<i>p</i> = 0.033), poor differentiation (<i>p</i> = 0.011), MSI-positive status (<i>p</i> < 0.0001), BRAF mutated tumors (<i>p</i> < 0.0001), and the loss of expression of mismatch-repair proteins MLH1 (<i>p</i> < 0.0001), MSH2 (<i>p</i> = 0.003), and PMS2 (<i>p</i> < 0.0001). Moreover, the presence of <i>Fn</i> DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; <i>p</i> = 0.028) and overall survival (63.5 vs. 76.5%; <i>p</i> = 0.037). Here we report, for the first time, the association of <i>F. nucleatum</i> presence with important clinical and molecular features in a Brazilian cohort of CRC patients. Tumor detection and classification based on the gut microbiome might provide a promising approach to improve the prediction of patient outcome.