Enterotypical Prevotella and three novel bacterial biomarkers in preoperative stool predict the clinical outcome of colorectal cancer

Abstract

Background A significant proportion of colorectal cancer (CRC) patients suffer from early recurrence and progression after surgical treatment. Although the gut microbiota is considered as a key player in the initiation and progression of CRC, most prospective studies have been focused on a particular pathobionts such as Fusobacterium nucleatum. Here, we aimed to identify novel prognostic bacteria for CRC by examining the preoperative gut microbiota through 16S ribosomal RNA gene sequencing. Results We collected stool samples from 333 patients with primary CRC within 2 weeks before surgery and followed up the patients for a median of 27.6 months for progression and 43.6 months for survival. The sequence and prognosis data were assessed using the log-rank test and multivariate Cox proportional hazard analysis. The gut microbiota was associated with the clinical outcomes of CRC patients (Pprogress = 0.011, Pdecease = 0.007). In particular, the high abundance of Prevotella, a representative genus of human enterotypes, indicated lower risks of CRC progression (P = 0.026) and decease (P = 0.0056), while the occurrence of Alistipes assigned to Bacteroides sp., Pyramidobacter piscolens, Dialister invisus, and Fusobacterium nucleatum indicated a high risk of progression. A microbiota-derived hazard score considering the five prognostic bacteria accurately predicted CRC progression in 1000 random subsamples; it outperformed widely accepted clinical biomarkers such as carcinoembryonic antigen and lymphatic invasion, after adjustment for the clinicopathological stage (adjusted HR 2.07 [95% CI, 1.61–2.64], P = 7.8e−9, C-index = 0.78). PICRUSt2 suggested that microbial pathways pertaining to thiamine salvage and L-histidine degradation underlie the different prognoses. Conclusions The enterotypical genus Prevotella was demonstrated to be useful in improving CRC prognosis, and combined with the four pathobionts, our hazard score based on the gut microbiota should provide an important asset in predicting medical outcomes for CRC patients.

Meta-analyses of host metagenomes from colorectal cancer patients reveal strong relationship between colorectal cancer-associated species

“…When using the more traditional approach of unifying all studies in a single dataset, we are able to identify a larger number of differentially abundant species in CRC, many of which have been associated to this condition in previous studies. 21,22,24,34–38,63–73 In contrast, the Random Forest method presented a more concise list of species that, when filtered based on the prevalence across all projects, showed a very similar species composition in CRC to the one observed by our third method, the co-abundance across multiple studies. These consistent findings throughout all three methods indicates that CRC is highly characterized by an specific microbiome composition.…”

“…The list included genera and species previously associated with CRC, including Fusobacterium , Gemella , Prevotella , Bacteroides , and Porphyromonas . From these CRC-associated species, 34,63–73 37 showed a LFC ≥ 1 compared to control samples. We also identified 14 species associated to the normal condition, most of which are probiotic or known to produce metabolites with anti-inflammatory properties.…”

Gut microbiome as a biomarker for predicting early recurrence of HBV‐related hepatocellular carcinoma

“…Studies have demonstrated that gut microbiota have a substantial effect on the treatment outcome and overall survival of cancer patients. For instance, Huh et al identified four microbes associated with colorectal cancer prognosis by analyzing the preoperative stool microbes of colorectal cancer patients and constructed a risk‐scoring system based on gut microbes, which can accurately predict the prognosis after colorectal cancer surgery 9 . Similarly, Derosa et al 40 discovered that gut Akkermansia muciniphila abundance was associated with the clinical efficacy of PD‐1 inhibitors in patients with non–small‐cell lung cancer.…”

“…The gut microbiome, the body's most significant micro‐ecosystem, plays a significant role in a number of gastrointestinal and liver diseases, controlling host metabolism, inflammation, and immunity 7 . Several studies have shown that the abundance of particular gut microbes is connected with the prognosis of cancer patients, and specific strains of bacteria can be used as biomarkers to predict the outcome and prognosis of cancer patients effectively 8–10 . Alterations in gut microbes have been demonstrated to be related to the development and progression of nonalcoholic hepatitis, cirrhosis, and HCC 11,12 .…”

Therapeutic Target Identification and Inhibitor Screening against Riboflavin Synthase of Colorectal Cancer Associated Fusobacterium nucleatum

“…Improved methods for detecting microorganisms and new insights into the human microbiome have led to a new perspective on several diseases, including CRC [ 6 , 7 , 8 ]. According to recent research, this cancer is linked with altered gut microbiota [ 9 ] and aided by the anaerobic gram-negative bacteria F. nucleatum [ 4 , 10 , 11 , 12 ]. It is often linked to advanced disease, chemoresistance, distant metastases, and a poor prognosis [ 13 , 14 , 15 ].…”