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

Abstract

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 Fusobacterium nucleatum ( Fn ) 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 Fusobacterium being the most abundant genus in the tumor tissue. In the validation dataset, Fn 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 ( p = 0.0033). Fn DNA in the tumor tissue was significantly associated with proximal tumors ( p = 0.001), higher depth of invasion ( p = 0.014), higher clinical stages ( p = 0.033), poor differentiation ( p = 0.011), MSI-positive status ( p < 0.0001), BRAF mutated tumors ( p < 0.0001), and the loss of expression of mismatch-repair proteins MLH1 ( p < 0.0001), MSH2 ( p = 0.003), and PMS2 ( p < 0.0001). Moreover, the presence of Fn DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; p = 0.028) and overall survival (63.5 vs. 76.5%; p = 0.037). Here we report, for the first time, the association of F. nucleatum 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.

Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer

“…Many studies show that Fusobacterium is more abundant in the intestines of CRC patients compared to the healthy individuals [32,33,36,38,42,45,46]. Comparation between CRC tissues and adjacent noncancer tissues also reveals that Fusobacterium is more abundant in the CRC tissues (Table 2) [ 30,36,37,43,44]. These studies indicate that there is a close relationship between Fusobacterium and CRC development.…”

“…The abundance of Leptotrichia is lower in CRC patients compared to healthy individuals [27]. After comparing the CRC tissues with adjacent non-cancer tissues, de Carvalho et al showed that the abundance of Leptotrichia is decreased in the CRC tissues [44]. However, Xu and Jiang instead found that Leptotrichia is more abundant in the CRC patients (Table 2) [46].…”

“…It is typically found in the human intestine and invades the lining of the human small intestine. Many studies revealed that Campylobacter is enriched in the CRC tissues compared to adjacent non-cancer tissues [37,44]. Meanwhile, the abundance of Campylobacter in the intestines of CRC patients is higher than that of healthy individuals (Table 2) [33,38,46].…”

“…It mainly resides in the human intestine, and some studies indicate that the abundance of Clostridium in the intestines of CRC patients is higher than that of healthy individuals [31,32,46]. Further, Clostridium population is significant enhanced in the CRC tissues compared to the adjacent non-cancer tissues (Table 2) [44]. In a test group including 781 subjects, the authors found that the abundance of C. symbiosum gradually increases from the colorectal adenoma (CRA), early CRC, to advanced CRC [105].…”

“…Thomas et al found that Bacteroides is abundant in the intestines of CRC patients compared to the healthy individuals [31], yet some studies found that Bacteroides is depleted in the intestines of CRC patients compared to the healthy individuals [34,35]. Gao et al also reported that Bacteroides is abundant in CRC tissues compared to adjacent non-cancer tissues [36]; however, Carvalho et al demonstrated that Bacteroides are depleted in CRC tissues compared to adjacent non-cancer tissues (Table 2) [44]. These differences may be due to the different species of Bacteroides existing in the intestines of CRC patients.…”