scholarly journals Association network analysis identifies enzymatic components of gut microbiota that significantly differ between colorectal cancer patients and healthy controls

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7315 ◽  
Author(s):  
Dongmei Ai ◽  
Hongfei Pan ◽  
Xiaoxin Li ◽  
Min Wu ◽  
Li C. Xia

The human gut microbiota plays a major role in maintaining human health and was recently recognized as a promising target for disease prevention and treatment. Many diseases are traceable to microbiota dysbiosis, implicating altered gut microbial ecosystems, or, in many cases, disrupted microbial enzymes carrying out essential physio-biochemical reactions. Thus, the changes of essential microbial enzyme levels may predict human disorders. With the rapid development of high-throughput sequencing technologies, metagenomics analysis has emerged as an important method to explore the microbial communities in the human body, as well as their functionalities. In this study, we analyzed 156 gut metagenomics samples from patients with colorectal cancer (CRC) and adenoma, as well as that from healthy controls. We estimated the abundance of microbial enzymes using the HMP Unified Metabolic Analysis Network method and identified the differentially abundant enzymes between CRCs and controls. We constructed enzymatic association networks using the extended local similarity analysis algorithm. We identified CRC-associated enzymic changes by analyzing the topological features of the enzymatic association networks, including the clustering coefficient, the betweenness centrality, and the closeness centrality of network nodes. The network topology of enzymatic association network exhibited a difference between the healthy and the CRC environments. The ABC (ATP binding cassette) transporter and small subunit ribosomal protein S19 enzymes, had the highest clustering coefficient in the healthy enzymatic networks. In contrast, the Adenosylhomocysteinase enzyme had the highest clustering coefficient in the CRC enzymatic networks. These enzymic and metabolic differences may serve as risk predictors for CRCs and are worthy of further research.

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Wanxin Liu ◽  
Ren Zhang ◽  
Rong Shu ◽  
Jinjing Yu ◽  
Huan Li ◽  
...  

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.


2020 ◽  
Author(s):  
Ningning Li ◽  
Chunmei Bai ◽  
Yuanzhi Guan ◽  
Lin Zhao ◽  
Yuping Ge ◽  
...  

Abstract Background The incidence and mortality of gastrointestinal tumors are high in China. Some studies suggested that the gut microbiota is also related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in patients with esophageal cancer, gastric cancer, and colorectal cancer and healthy controls. Methods Patients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction.Results Significant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients and healthy controls. The abundance of F. prausnitzii, C. clostridioforme, and B. adolescents in three different tumor groups was all significantly lower than in the control group (P<0.05). The abundance of R. gnavus, B. obeum, and R. faecis in the gastric and colorectal cancer groups was significantly lower than in the control group (P<0.05). The abundance of Dorea in the gastric cancer group was significantly lower than in the control group (P<0.05). B. fragilis, P. corpi, and E. coli were overabundant in the different tumor groups compared with the control (P<0.05). There were significant differences in functional metabolism and cell biological function between the tumor and control groups (P<0.05). The feces of cancer patients with more advanced staging had higher abundance of Prevotella and fewer Clostridium. Conclusions Patients with esophageal or gastric cancer had similar features of fecal bacteria as those with colorectal cancer. The metabolic function of fecal bacteria in the gastrointestinal cancer patients and the healthy controls were different.


2021 ◽  
Vol 9 (8) ◽  
pp. 1548
Author(s):  
Chuan-Yin Fang ◽  
Jung-Sheng Chen ◽  
Bing-Mu Hsu ◽  
Bashir Hussain ◽  
Jagat Rathod ◽  
...  

Despite advances in the characterization of colorectal cancer (CRC), it still faces a poor prognosis. There is growing evidence that gut microbiota and their metabolites potentially contribute to the development of CRC. Thus, microbial dysbiosis and their metabolites associated with CRC, based on stool samples, may be used to advantage to provide an excellent opportunity to find possible biomarkers for the screening, early detection, prevention, and treatment of CRC. Using 16S rRNA amplicon sequencing coupled with statistical analysis, this study analyzed the cause–effect shift of the microbial taxa and their metabolites that was associated with the fecal gut microbiota of 17 healthy controls, 21 polyps patients, and 21 cancer patients. The microbial taxonomic shift analysis revealed striking differences among the healthy control, polyps and cancer groups. At the phylum level, Synergistetes was reduced significantly in the polyps group compared to the healthy control and cancer group. Additionally, at the genus level and in association with the cancer group, a total of 12 genera were highly enriched in abundance. In contrast, only Oscillosprira was significantly higher in abundance in the healthy control group. Comparisons of the polyps and cancer groups showed a total of 18 significantly enriched genera. Among them, 78% of the genera associated with the cancer group were in higher abundance, whereas the remaining genera showed a higher abundance in the polyps group. Additionally, the comparison of healthy control and polyp groups showed six significantly abundant genera. More than 66% of these genera showed a reduced abundance in the polyps group than in healthy controls, whereas the remaining genera were highly abundant in the polyps group. Based on tumor presence and absence, the abundance of Olsenella and Lactobacillus at the genus level was significantly reduced in the patient group compared to healthy controls. The significant microbial function prediction revealed an increase in the abundance of metabolites in the polyps and cancer groups compared to healthy controls. A correlation analysis revealed a higher contribution of Dorea in the predicted functions. This study showed dysbiosis of gut microbiota at the taxonomic level and their metabolic functions among healthy subjects and in two stages of colorectal cancer, including adenoma and adenocarcinoma, which might serve as potential biomarkers for the early diagnosis and treatment of CRC.


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