Abstract
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Purpose
- This study aimed to determine the effect of tumor resection on dysbiosis of the intestinal microbiota in patients with right-sided colon cancer.
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Methods
- This study utilized a longitudinal design to explore the outcomes of patients diagnosed with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. We excluded patients with a documented history of comorbidities, specifically those affecting the digestive system. To compare the microbiota (genus and phylum) between patients with right-sided colon cancer and the control group, we conducted bivariate analyses using the independent t-test or Mann-Whitney test. Furthermore, we employed the dependent t-test or Wilcoxon test to assess changes in the dysbiosis of the microbiota (genus and phylum) before and after resection. A P-value of <0.05 was considered statistically significant.
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Results
- This study included a total of 21 patients diagnosed with right-sided colon cancer. In the control group, Bacteroidetes constituted the highest proportion of intestinal microbiota, accounting for 56.34%. Prior to tumor resection, the intestinal microbiota of patients exhibited Proteobacteria as the predominant phylum, representing 52.97%. Following tumor resection, Bacteroidetes remained the most prevalent, comprising 50.9% of the intestinal microbiota. Significant variations in the levels of Proteobacteria, Verrucomicrobia, and Cyanobacteria/Chloroplast were observed in the intestinal microbiota of patients with right-sided colorectal cancer before and after tumor excision (all P=0.001).
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Conclusion
- The microbiome of patients with right-sided colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients became more similar to that observed in the control group.
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Keywords: Dysbiosis; Right-sided colon cancer; Microbiota; Resection
Graphical abstract
INTRODUCTION
Colorectal cancer ranks as the third most common cancer among men and the second most common among women globally. According to 2020 data from GLOBOCAN, there are an estimated 1.93 million new cases of colorectal cancer and 0.94 million deaths due to colorectal cancer worldwide [1]. In Indonesia, GLOBOCAN data from the same year show that colorectal cancer accounted for 34,189 cases, or 8.6% of all cancer cases. Of these, 21,764 cases were in men and 12,425 in women [2].
Colorectal cancer can typically be categorized into 3 types: right-sided colon cancer, left-sided colon cancer, and rectal cancer. Mutations in the DNA mismatch repair pathway are commonly observed in right-sided colon cancer, which is often characterized by a flat histology [3]. Biologically, right and left-sided colon cancers exhibit distinct characteristics. The right colon shows a higher incidence of high microsatellite instability, CpG island methylator phenotype–high, and BRAF mutations, along with a greater prevalence of sessile serrated polyps. Conversely, the left colon more frequently presents with tubular adenomas and shows increased expression of epiregulin and amphiregulin, along with a higher occurrence of consensus molecular subtypes 2 and 4 [4].
The etiology of right-sided colon cancer is highly complex, involving both genetic and environmental factors [5]. Among these, the intestinal microbiota emerges as a crucial contributor to the development of colorectal cancer, particularly in the right colon. Intestinal microbiota or its derived metabolites may act as direct environmental modifiers in a process known as dysbiosis. Recent research increasingly supports the significant role of intestinal microbiota in the initiation, progression, and metastasis of right-sided colon cancer [6–8].
The human intestinal microbiota comprises 1013 to 1014 microbes, outnumbering human cells by a factor of 10 and possessing 100 times more genes than the human genome. In healthy individuals, intestinal microbiota is crucial for energy production, formation of the intestinal epithelium, protection against pathogens, and maintenance of immune function. Conversely, dysbiosis of the intestinal microbiota can impair the host's physiological functions and lead to various diseases [6, 9, 10].
There is strong evidence that the composition of intestinal microbiota can initiate tumorigenesis. Several studies have observed differences in the number and composition of microbiota between healthy individuals and those with colorectal cancer, particularly noting changes in the general population and specifically in the right colon [3]. The exact relationship between microbiota and tumorigenesis remains unclear. However, there is a hypothesis that certain microbiota may cause chronic inflammation in the epithelium of the colorectal area. This inflammation could be triggered by toxins released by these bacteria, which in turn lead to the production of pro-inflammatory cytokines, suppression of antitumor T-cell immunity, and enhanced tumor growth via the NF-κB pathway [11].
The intestinal microbiota plays a crucial role in the development of right-sided colon cancer by disrupting microenvironmental homeostasis, modifying immune responses, generating toxic metabolites, and influencing epigenetic modifications both directly and indirectly. Various bacterium types have been identified as promoters of right-sided colon cancer through different pathways and mechanisms. As a biomarker, the intestinal microbiota offers a novel approach for the early, noninvasive diagnosis of colorectal cancer. Additionally, the analysis of intestinal flora in feces can aid in predicting colorectal cancer [12]. Based on the explanation outlined above, it has become apparent that the relationship between colorectal cancer and the composition of the intestinal microbiota is also affected by the cancer's location [3].
A study conducted in Japan compared 12 patients with appendicitis to 13 patients who underwent ileocecal resection or right hemicolectomy for colon cancer, using the latter group as a control. The microbiota were analyzed through next-generation sequencing of appendix swab samples collected postoperatively. The research found no significant changes in the distribution and variation of the existing microbiota species [13]. Therefore, the issues discussed above have raised new questions that motivated this research, stemming from frequent encounters with right-sided colon cancer and various theories proposing different contributing factors to the disease's development. One such factor is the dysbiosis of the intestinal microbiota. While numerous studies have been conducted, they have predominantly been conducted in more developed regions such as America, Europe, and Asia, rather than in Indonesia. Notably, no research on this topic has been conducted in Indonesia that encompasses patient characteristics, methodology, and results. This gap highlights the need for conducting this research. Extending or adapting this research to reflect the unique attributes of each community would be beneficial.
METHODS
Ethics statement
The study’s protocol was approved by the Ethics Committee of the Faculty of Medicine, Universitas Andalas (No. 74/UN.16.2/KEP-FK/2024). Written informed consent was obtained from the patients.
Study design
This study employed a consecutive sampling method. It included all patients with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital (Padang, Indonesia) from July to December 2023 and met the inclusion criteria. Sampling continued until the minimum sample size was achieved.
Description of participants
All patients diagnosed with right-sided colon cancer at Dr. M. Djamil General Hospital between July and December 2023, who underwent surgical resection and met the specified inclusion and exclusion criteria, were included in the study until the required minimum sample size was reached. The inclusion criteria for the sample group were patients who underwent tumor resection at Dr. M. Djamil General Hospital and expressed willingness to participate in the research. The inclusion criteria for the control group were individuals without changes in bowel habits, as confirmed by the Bristol Stool Form Scale, and without complaints related to the digestive system, who also agreed to participate in the research. All members of the control group were surgical residents. The exclusion criteria for this study included patients with comorbidities involving other digestive system diseases. Using the Lemeshow formula, the minimum sample size determined for this research was 19. However, during the study period, we obtained that met all inclusion criteria.
Data collection
This research used primary data that were collected from direct observations of patients. This included demographic information, patient characteristics, and descriptions of intestinal microbiota dysbiosis before and after tumor resection. It is essential that patient stool samples be collected both before and after the tumor resection procedure. Each sample should be placed in a dry, clean, and leak-proof tube and stored in a refrigerator prior to examination. The examination of intestinal microbiota dysbiosis in patients pre- and post-tumor resection was conducted using next-generation sequencing [14]. In this study, sampling after the procedure was carried out 3 weeks after the patient had surgery or during the patient's first visit to the clinic. The initial polymerase chain reaction (PCR) process involved 16S ribosomal RNA (rRNA) sequencing, followed by index PCR in the subsequent step. For the first step of next-generation sequencing, the laboratory processed a stool sample ranging from 200 to 220 mg, storing any remaining sample in a freezer. Subsequently, DNA was isolated from the stool and its concentration was measured using a Qubit (Thermo Fisher Scientific Inc) to ensure a minimum of 5 ng/mL. The first stage of PCR was then carried out to amplify the DNA template. Following amplification, the first post-PCR wash was performed using AMPure XP Beads (Beckman Coulter Inc) to purify the 16S V3 and V4 regions from primer dimer species. In the second post-PCR wash, DNA was paired with double indexes using the Nextera XT Index Kit (Illumina Inc), and purification was again achieved with AMPure XP Beads. The DNA concentration was then quantified to ensure it reached up to 4 nM, and the pH was adjusted to 8.5 for optimal processing. Denaturation and dilution were carried out using PhiX Control (Illumina Inc) and an amplicon library before loading the sample into the MiSeq flow cell. After processing, the MiSeq Reporter Software (Illumina Inc) analyzed and classified the 16S rRNA sequences according to the Greengenes database. The output included taxonomic classification at various levels—kingdom, phylum, class, order, family, genus, and species—accompanied by a table of sample numbers, a graph of clusters passing the filter, information on the presence or absence of duplicates, and a presentation of the classification results for each sample.
Data analysis
The data analysis conducted in this research comprised both univariate and bivariate methods. The univariate analysis aimed to provide a descriptive overview of each variable. Specifically, for variables measured on a numerical scale, such as intestinal microbiota dysbiosis, descriptive statistical tables were employed to present the minimum, maximum, average, and standard deviation values. Bivariate analysis was performed using either the independent t-test or the Mann-Whitney U-test. This analysis focused on comparing the differences in intestinal microbiota composition between healthy individuals and cancer patients, both before and after tumor resection. Prior to conducting the analysis, the data were tested for normality using the Shapiro-Wilk test, appropriate for sample sizes smaller than 50 per group. Data are considered normally distributed if the significance value exceeds 0.05. In cases of normal distribution, the independent t-test was applied. Conversely, for data not normally distributed, the Mann-Whitney U-test served as the nonparametric alternative. A P-value of 0.05 indicates a statistically significant difference.
Bivariate analysis was conducted using the dependent t-test or the Wilcoxon test to analyze differences in intestinal microbiota composition between groups (cancer patients before and after resection). The dependent t-test was applied if the data were normally distributed. Conversely, if the data were not normally distributed, the nonparametric Wilcoxon test was used, also with a P-value of <0.05 indicating statistical significance.
RESULTS
Patient characteristics
The sample in this study consisted of 2 groups: the sample group and the control group. The sample group comprised 21 patients with right-sided colon cancer who underwent surgical resection at Dr. M. Djamil General Hospital from July to December 2023. The control group included 20 healthy individuals without any changes in bowel habits or digestive system complaints, who volunteered to participate in the research.
Table 1 reveals that patients with right-sided colon cancer who underwent surgical therapy were predominantly aged 41 to 60 years (57.1%), female (57.1%), with high school or college education (42.9%), and employed as housewives (42.9%). All of the patients followed a low-fiber diet, 18 (85.7%) had no history of diabetes mellitus, and 14 (66.7%) were nonsmokers. In contrast, the control group, consisting of healthy individuals, included only those aged 20 to 40 years (100%), predominantly male (95%), all with a college education (100%), and working as surgical residents (100%). None of the individuals in the control group followed a low-fiber diet, had diabetes mellitus, or smoked. The statistical analysis indicated significant differences in age, sex, education, occupation, dietary habits, and smoking status between the cancer patients and the healthy control group (all P<0.05). However, there was no significant difference in the prevalence of diabetes mellitus between the 2 groups (P=0.232).
Analysis based on the level of phylum classification
Univariate analysis was conducted to describe the intestinal microbiota across the top 10 phylum groups. Fig. 1 illustrates that in the control group of healthy individuals, the predominant phylum was Bacteroidetes, constituting 56.34% of the intestinal microbiota. In the pre-tumor resection group, the most abundant phyla were Proteobacteria, at 52.97%, and Firmicutes, at 26.40%. Following tumor resection, the post-tumor resection group showed that Bacteroidetes remained the most prevalent, comprising 50.90% of the intestinal microbiota.
Table 2 shows that the mean percentage of intestinal microbiota was higher in the control group than in the pre-resection group of right-sided colon cancer patients for the following taxa: the phylum Bacteroidetes (56.34% vs. 15.74%), the phylum Firmicutes (32.00% vs. 26.40%), the phylum Acidobacteria (0.03% vs. 0.02%), the phylum Armatimonadetes (0.02% vs. 0.01%), the phylum Chloroflexi (0.01% vs. 0.01%), and other groups (1.15% vs. 0.98%). Statistical analysis revealed significant differences in the intestinal microbiota between the control and pre-resection groups across several phyla: Proteobacteria (P<0.001), Actinobacteria (P=0.035), Verrucomicrobia (P<0.001), and Cyanobacteria/Chloroplast (P<0.001)
The mean percentage of intestinal microbiota was higher in the pre-resection group compared to the control group for the following taxa: the phylum Proteobacteria (52.97% vs. 9.16%), the phylum Actinobacteria (0.78% vs. 0.64%), the phylum Verrucomicrobia (2.63% vs. 0.58%), the phylum Cyanobacteria/Chloroplast (0.46% vs. 0.07%). Statistical testing showed significant differences between the control group and the pre-resection group in the intestinal microbiota across several phyla: Proteobacteria (P<0.001), Actinobacteria (P=0.035), Verrucomicrobia (P<0.001), and Cyanobacteria/Chloroplast (P<0.001)
Table 2 also shows that the mean percentage of intestinal microbiota was higher in the control group than in the post-resection group of right-sided colon cancer patients for the following taxa: the phylum Bacteroidetes (56.34% vs. 50.90%), the phylum Firmicutes (32.0% vs. 26.67%), the phylum Actinobacteria (0.64% vs. 0.63%), the phylum Acidobacteria (0.03% vs. 0.02%), the phylum Armatimonadetes (0.02% vs. 0.01%), the phylum Chloroflexi (0.01% vs. 0.01%) and other groups (1.15% vs. 0.92%). However, statistical tests indicated no significant differences in the intestinal microbiota across the phyla Bacteroidetes, Firmicutes, Actinobacteria, Acidobacteria, Armatimonadetes, Chloroflexi, and other groups between the control and post-resection groups (P>0.05).
The mean percentage of intestinal microbiota was higher in the post-resection group than in the control group for the following taxa: the phylum Proteobacteria (19.87% vs. 9.16%), the phylum Verrucomicrobia (0.85% vs. 0.58%), and the phylum Cyanobacteria/Chloroplast (0.11% vs. 0.07%). The statistical analysis showed significant differences between the control and post-resection groups in the intestinal microbiota for the phyla Proteobacteria (P=0.008), Actinobacteria (P=0.035), and Verrucomicrobia (P=0.047).
Table 3 shows that the mean percentage of intestinal microbiota was higher in the post-resection group than in the pre-resection group for the following taxa: the phylum Bacteroidetes (50.90% vs. 15.74%), the phylum Firmicutes (26.67% vs. 26.40%), the phylum Armatimonadetes (0.01% vs. 0.01%), and the phylum Chloroflexi (0.01% vs. 0.01%). Statistical analysis revealed a significant difference in the intestinal microbiota of the phylum Bacteroidetes before and after resection in patients with right-sided colon cancer (P=0.001).
The mean percentage of intestinal microbiota was higher in the pre-resection group than in the post-resection group for the following taxa: the phylum Proteobacteria (52.97% vs. 19.87%), the phylum Actinobacteria (0.78% vs. 0.63%), the phylum Verrucomicrobia (2.63% vs. 0.85%), the phylum Cyanobacteria/Chloroplast (0.46% vs. 0.11%), the phylum Acidobacteria (0.02% vs. 0.02%), and other groups (0.98% vs. 0.92%). Statistical testing showed differences in the intestinal microbiota between the pre- and post-resection analyses in right-sided colon cancer for the following phyla: Proteobacteria (P=0.001), Verrucomicrobia (P=0.011), and Cyanobacteria/Chloroplast (P=0.001).
Analysis based on the level of genus classification
Univariate analysis was conducted to describe the intestinal microbiota within the top 10 genus groups. Fig. 2 illustrates that in the control group of healthy individuals, the predominant genus was Prevotella, comprising 25.10% of the intestinal microbiota. In the pre-tumor resection group, Bacteroides was the most prevalent genus, representing 7.18% of the microbiota. Following tumor resection, the proportion of Bacteroides in the intestinal microbiota increased to 21.31% in the post-tumor resection group.
Table 4 shows that the mean percentage of intestinal microbiota was higher in the control group than in the pre-resection group of right-sided colon cancer patients for the following genera: Clostridium sensu stricto (1.17% vs. 0.99%), Prevotella (25.10% vs. 2.27%), Bacteroides (17.56% vs. 7.18%), Streptococcus (0.08% vs. 0.07%), Desulfovibrio (0.13% vs. 0.13%), and Porphyromonas (0.05% vs. 0.01%). The statistical test results showed differences in the intestinal microbiota of the genera Prevotella (P=0.014), Bacteroides (P=0.035), and Porphyromonas (P<0.001) between the control group and the pre-resection group.
The mean percentage of intestinal microbiota was higher in the pre-resection group than in the control group for the following genera: Lactobacillus (2.12% vs. 0.34%), Clostridium XlVa (0.39% vs. 0.31%), Streptophyta (0.46% vs. 0.06%), and other groups (86.37% vs. 55.19%). The statistical test analysis demonstrated significant differences in the intestinal microbiota between the control group and the pre-resection group for the following genera: Lactobacillus (P<0.001), Streptophyta (P<0.001), and other groups (P<0.001)
Table 4 also shows that the mean percentage of intestinal microbiota was higher in the control group than in the post-resection group of right-sided colon cancer patients for the following genera: Clostridium sensu stricto (1.17% vs. 0.61%), Prevotella (25.10% vs. 17.26%), Clostridium XlVa (0.31% vs. 0.18%), Desulfovibrio (0.13% vs. 0.08%), and Porphyromonas (0.05% vs. 0.03%). Statistical analysis revealed significant differences in the levels of the genus Porphyromonas between the control and post-resection groups (P=0.028).
The mean percentage of intestinal microbiota was higher in the post-resection group than in the control group for the following genera: Bacteroides (21.31% vs. 17.56%), Lactobacillus (0.71% vs. 0.34%), Streptococcus (0.12% vs. 0.08%), Streptophyta (0.10% vs. 0.06%), and other groups (59.61% vs. 55.19%). Statistical testing showed a significant difference in the intestinal microbiota of the genus Lactobacillus (P=0.007) between the control group and the post-resection group.
Table 5 shows that the mean percentage of intestinal microbiota was higher in the post-resection group than in the pre-resection group for the following genera: Prevotella (17.26% vs. 2.27%), Bacteroides (21.31% vs. 7.18%), Streptococcus (0.12% vs. 0.07%), and Porphyromonas (0.03% vs. 0.01%). Statistical analysis showed differences in the intestinal microbiota between before and after resection in right-sided colon cancer patients for the genera Prevotella (P=0.001), Bacteroidetes (P=0.002), and Porphyromonas (P=0.008).
The mean percentage of intestinal microbiota was higher in the pre-resection group than in the post-resection group for the following genera: Clostridium sensu stricto (0.99% vs. 0.61%), Lactobacillus (2.12% vs. 0.71%), Clostridium XlVa (0.39% vs. 0.18%), Desulfovibrio (0.13% vs. 0.08%), Streptophyta (0.46% vs. 0.10%), and other groups (86.37% vs. 59.61%). Statistical testing showed differences in the intestinal microbiota between the pre- and post-resection samples in right-sided colon cancer patients for the genera Lactobacillus (P=0.018), Clostridium XlVa (P=0.001), Streptophyta (P=0.001), and other groups (P=0.001).
DISCUSSION
Analysis of differences in intestinal microbiota dysbiosis in right-sided colon cancer patients before and after tumor resection procedures
Intestinal microbiota plays a pivotal role as an environmental factor in various cancers, including colorectal cancer and, more specifically, right-sided colon cancer [15]. The intestinal microbiota phyla most commonly found in the pre-tumor resection group were the phylum Proteobacteria (52.97%) and the phylum Firmicutes (26.40%). Suga et al. [3] found that Bacteroides was the most abundant bacterial phylum in patients with right-sided colon cancer before resection (37.5%±18.9%) [3]. Suga et al. [3] reported findings that align with those of Kneis et al. [16], where the most abundant microbiota in right-sided colon cancer were Bacteroides (15%), Ruminococcus2 (10%), Blautia (8%), Peptostreptococcus (7%), and Veillonella (5%).
Our research found that the most intestinal microbiota in the post-tumor resection group was the phylum Bacteroidetes (50.9%). Research conducted by Suga et al. [3] found that the most abundant bacteria after resection were the phylum Bacteroidetes (50.1%±11.2%). Png et al. [17] reported that the bacterial phyla Firmicutes, Actinobacteria, Verrucomicrobia, and Bacteroidetes were the most commonly found in both pre- and post-resection tumors.
The number of beneficial obligate anaerobic bacteria, such as Bacteroides, Bifidobacterium, Faecalibacterium, Parabacteroides, and Prevotella, decreased in the post-resection group [18]. Tumor-associated microbiota such as Enterococcus and Fusobacterium also decreased, as did obligate anaerobic bacteria such as Prevotella also decreased after surgery. These changes suggest that microbiota dysbiosis is linked to cancer, and that tumor resection not only removes the lesion but also helps reverse the dysbiosis associated with colorectal cancer [17].
There were decreases in the percentage of Firmicutes (41% vs. 29%) and Bacteroidetes (51% vs. 60%) after tumor resection (P<0.001). Post-resection, there was a significant increase in Enterococcus (P<2.20×109) [17]. A randomized controlled trial that investigated the impact of preoperative factors on the postoperative composition of the intestinal microbiota in colorectal cancer patients revealed intestinal dysbiosis characterized by a reduction in the total number of bacteria, particularly Bacteroides and Peptostreptococcus. A decrease in the ratio of Bacteroidetes to Firmicutes can contribute to intestinal inflammation [18].
Our analysis revealed differences in the intestinal microbiota of the phylum Bacteroidetes between pre- and post-tumor resection in right-sided colon cancer patients (P=0.001), as well as in the phyla Proteobacteria (P=0.001), Verrucomicrobia (P=0.011), and Cyanobacteria/Chloroplast (P=0.001). Suga et al. [3] found that the microbiota after resection was less diverse than that observed right-sided colon cancer patients who did not undergo resection (P<0.05). Png et al. [17] stated that there were differences in the intestinal microbiota before and after surgery, specifically noting an increase in probiotic bacteria.
Comparative analysis of intestinal microbiota dysbiosis in normal individuals and right-sided colon cancer patients
Suga et al. [3] identified differences in the microbiota between the control group and the right-sided colon cancer group (P<0.01). The cancer group had a greater diversity of species, with fewer protective phyla (e.g., Roseburia) and higher levels of carcinogenic phyla (in the form of Bacteroides, Escherichia, Fusobacterium, and Porphyromas) than the control group [15].
In this study, the predominant intestinal microbiota in the control group was the phylum Bacteroidetes. In contrast, the pre-resection group showed predominance of the phyla Proteobacteria and Firmicutes, while the post-resection group again exhibited dominance of the phylum Bacteroidetes. Suga et al. [3] found that the most abundant phylum were Bacteroidetes and Clostridium XIVa both in the pre- and post-resection control groups. Li et al. [19] identified 6 genera—namely, Fusobacterium, Gemella, Campylobacter, Peptostreptococcus, Alloprevotella, and Parvimonas—that increased in tumor mucosa compared to normal mucosa. The composition of the microbiota in patients with colorectal cancer compared with healthy patients showed higher levels of Enterococcus, Faecalibacterium, Staphylococcus, Streptococcus, Prevotella, Escherichia, Klebsiella, Shigella, Fusobacterium and lower levels of Clostridium, Lactobacillus, Roseburia, Bacteroides, Bifidobacterium. No changes were found in some bacteria, namely Bacillus, Barnesiella, Parabacteroides, Bilophila, and Pseudomonas [18]. Escherichia, Enterococcus, Bacteroides, and Clostridium may promote colorectal carcinogenesis by increasing aberrant crypt foci induced by 1,2-dimethylhydrazine [19].
Our analysis revealed differences in the intestinal microbiota between the control group and the pre-resection group for the phyla Bacteroidetes (P<0.001), Armatimonadetes (P=0.005), Proteobacteria (P<0.001), Actinobacteria (P=0.035), Verrucomicrobia (P<0.001), and Cyanobacteria/Chloroplast (P<0.001). Similarly, differences were observed between the control group and the post-resection group for the phyla Proteobacteria (P=0.008), Actinobacteria (P= 0.035), and Verrucomicrobia (P=0.047). Research by Kneis et al. [16] found no significant differences in the microbiota between tumor tissue and healthy tissue, which is supported by several other studies that found similar results. Suga et al. [3] found that Firmicutes and Bacilli were more abundant in patients with right-sided colon cancer than in the control group. However, Fusobacteria did not exhibit significant differences between the 2 groups. Colonic dysbiosis contributes to the pathogenesis of colorectal cancer by inducing inflammation through increased bacterial potential for inflammation [20]. Bacteria detected in colorectal cancer biofilms have invasive capabilities [19].
Pathogens such as Streptococcus bovis, enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, Enterococcus faecalis, Escherichia coli, and Peptostreptococcus anaerobius are considered potential contributors to colorectal cancer due to their involvement in inflammation associated with the intestinal microbiota. The procarcinogenic properties of bacterial microbiota, which include the induction of inflammation, biosynthesis of genotoxins, and interference with cell cycle regulation, have been documented [20].
Limitations
A limitation of this study is the imbalance in characteristics such as age, sex, smoking history, education, occupation, and dietary fiber intake, which could introduce significant bias. The composition of the gut microbiome changes with age, and environmental factors significantly impact it.
Conclusions
The microbiome of patients with right colorectal cancer differed significantly from that of the control group. However, following tumor resection, the microbiome composition of these patients began to resemble that of the control group more closely.
ARTICLE INFORMATION
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Conflict of interest
No potential conflict of interest relevant to this article was reported.
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Funding
None.
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Author contributions
Conceptualization: AMP; Data curation: AMP, MIR, RS, IAR, AS; Formal analysis: AMP, MIR, RS; Funding acquisition: MIR, RS; Investigation: AMP; Methodology: RS, AEP; Visualization: AMP, RS; Writing–original draft: AMP, MIR, RS; Writing–review & editing: all authors. All authors read and approved the final manuscript.
Fig. 1.Intestinal microbiota in the control, pre-resection, and post-resection groups based on the phylum level. In the control group (healthy individuals), the highest proportion of intestinal microbiota was found for the phylum Bacteroidetes (56.34%). In the pre-tumor resection group, the highest proportion of intestinal microbiota was found for the Proteobacteria phylum (52.97%) and the Firmicutes phylum (26.40%). Then, in the post-tumor resection group, the highest proportion of intestinal microbiota was found for the phylum Bacteroidetes (50.90%).
Fig. 2.Intestinal microbiota in the control, pre-resection, and post-resection groups based on the genus level. In the control group (healthy individuals), the highest proportion of intestinal microbiota was found for the genus Prevotella (25.10%). In the pre-tumor resection group, the highest proportion of intestinal microbiota was found for the genus Bacteroides (7.18%). Then, in the post-tumor resection group, the highest proportion of intestinal microbiota was found for the genus Bacteroides (21.31%).
Table 1.Characteristics of right-sided colon cancer patients undergoing surgical therapy and healthy individuals
|
Characteristic |
No. of patients (%)
|
P-value |
|
Right-sided colon cancer group (n=21) |
Control group (n=20) |
|
Age (yr) |
|
|
<0.001 |
|
20–40 |
6 (28.6) |
20 (100) |
|
|
41–60 |
12 (57.1) |
0 (0) |
|
|
>60 |
3 (14.3) |
0 (0) |
|
|
Sex |
|
|
0.001 |
|
Male |
9 (42.9) |
19 (95.0) |
|
|
Female |
12 (57.1) |
1 (5.0) |
|
|
Education |
|
|
<0.001 |
|
Elementary school |
3 (14.2) |
0 (0) |
|
|
High school |
9 (42.9) |
0 (0) |
|
|
College |
9 (42.9) |
20 (100) |
|
|
Occupation |
|
|
<0.001 |
|
Housewife |
9 (42.9) |
0 (0) |
|
|
Farmer |
3 (14.3) |
0 (0) |
|
|
Self-employed |
7 (33.3) |
0 (0) |
|
|
Retired |
2 (9.5) |
0 (0) |
|
|
Surgical resident |
0 (0) |
20 (100) |
|
|
Low-fiber diet |
|
|
<0.001 |
|
Yes |
21 (100) |
0 (0) |
|
|
No |
0 (0) |
20 (100) |
|
|
History of diabetes mellitus |
|
|
0.232 |
|
Yes |
3 (14.3) |
0 (0) |
|
|
No |
18 (85.7) |
20 (100) |
|
|
Smoking behavior |
|
|
0.009 |
|
Yes |
7 (33.3) |
0 (0) |
|
|
No |
14 (66.7) |
20 (100) |
|
Table 2.Comparison of intestinal microbiota in the control, pre-resection, and post-resection groups of patients with right-sided colon cancer (phylum level)
|
Intestinal microbiota |
Control (n=20) |
Pre-resection (n=21) |
P-value |
Post-resection (n=21) |
P-value |
|
Bacteroidetes (%) |
56.34±15.28 |
15.74±14.25 |
<0.001a*
|
50.90±17.66 |
0.299b
|
|
Firmicutes (%) |
32.00±13.09 |
26.40±7.88 |
0.103b
|
26.67±9.17 |
0.137b
|
|
Proteobacteria (%) |
9.16±9.91 |
52.97±19.87 |
<0.001a*
|
19.87±17.02 |
0.008a
|
|
Actinobacteria (%) |
0.64±0.59 |
0.78±0.18 |
0.035a*
|
0.63±0.48 |
0.657a
|
|
Verrucomicrobia (%) |
0.58±1.79 |
2.63±1.81 |
<0.001a*
|
0.85±1.58 |
0.047a
|
|
Cyanobacteria/Chloroplast (%) |
0.07±0.14 |
0.46±0.26 |
<0.001a*
|
0.11±0.27 |
0.706a
|
|
Acidobacteria (%) |
0.03±0.02 |
0.02±0.01 |
0.466a
|
0.02±0.01 |
0.305a
|
|
Armatimonadetes (%) |
0.02±0.01 |
0.01±0.00 |
0.005a
|
0.01±0.01 |
0.346a
|
|
Chloroflexi (%) |
0.01±0.01 |
0.01±0.00 |
0.279a
|
0.01±0.00 |
0.509a
|
|
Other (%) |
1.15±0.65 |
0.98±0.39 |
0.449a
|
0.92±0.42 |
0.159a
|
Table 3.Comparison of intestinal microbiota dysbiosis in the pre- and post-resection groups of right-sided colon cancer patients (phylum level)
|
Intestinal microbiota |
Pre-resection (n=20) |
Post-resection (n=21) |
P-value |
|
Bacteroidetes (%) |
15.74±14.25 |
50.90±17.66 |
0.001a*
|
|
Firmicutes (%) |
26.40±7.88 |
26.67±9.17 |
0.931b
|
|
Proteobacteria (%) |
52.97±19.87 |
19.87±17.02 |
0.001a*
|
|
Actinobacteria (%) |
0.78±0.18 |
0.63±0.48 |
0.154a
|
|
Verrucomicrobia (%) |
2.63±1.81 |
0.85±1.58 |
0.011a*
|
|
Cyanobacteria/Chloroplast (%) |
0.46±0.26 |
0.11±0.27 |
0.001a*
|
|
Acidobacteria (%) |
0.02±0.01 |
0.02±0.01 |
0.717a
|
|
Armatimonadetes (%) |
0.01±0.00 |
0.01±0.01 |
0.097a
|
|
Chloroflexi (%) |
0.01±0.00 |
0.01±0.00 |
0.083a
|
|
Other (%) |
0.98±0.39 |
0.92±0.42 |
0.520a
|
Table 4.Comparison of intestinal microbiota in the control, pre-resection, and post-resection groups of right-sided colon cancer patients (genus level)
|
Intestinal microbiota |
Control (n=20) |
Pre-resection (n=21) |
P-value |
Post-resection (n=21) |
P-value |
|
Clostridium sensu stricto (%) |
1.17±1.52 |
0.99±1.09 |
0.514 |
0.61±0.37 |
0.593 |
|
Prevotella (%) |
25.10±28.14 |
2.27±2.48 |
0.014*
|
17.26±18.26 |
0.804 |
|
Bacteroides (%) |
17.56±16.22 |
7.18±5.94 |
0.035*
|
21.31±15.13 |
0.285 |
|
Lactobacillus (%) |
0.34±0.81 |
2.12±2.80 |
<0.001*
|
0.71±0.83 |
0.007*
|
|
Clostridium XlVa (%) |
0.31±0.24 |
0.39±1.21 |
0.175 |
0.18±0.10 |
0.078 |
|
Streptococcus (%) |
0.08±0.11 |
0.07±0.05 |
0.617 |
0.12±0.12 |
0.176 |
|
Desulfovibrio (%) |
0.13±0.15 |
0.13±0.18 |
0.773 |
0.08±0.13 |
0.26 |
|
Streptophyta (%) |
0.06±0.13 |
0.46±0.26 |
<0.001*
|
0.10±0.27 |
0.157 |
|
Porphyromonas (%) |
0.05±0.04 |
0.01±0.02 |
<0.001*
|
0.03±0.02 |
0.028*
|
|
Other (%) |
55.19±18.36 |
86.37±9.40 |
<0.001*
|
59.61±14.65 |
0.958 |
Table 5.Comparison of intestinal microbiota dysbiosis in the pre- and post-resection groups of right-sided colon cancer patients (genus level)
|
Intestinal microbiota |
Pre-resection (n=20) |
Post-resection (n=21) |
P-value |
|
Clostridium sensu stricto (%) |
0.99±1.09 |
0.61±0.37 |
0.140a
|
|
Prevotella (%) |
2.27±2.48 |
17.26±18.26 |
0.001a*
|
|
Bacteroides (%) |
7.18±5.94 |
21.31±15.13 |
0.002a*
|
|
Lactobacillus (%) |
2.12±2.80 |
0.71±0.83 |
0.018a*
|
|
Clostridium XlVa (%) |
0.39±1.21 |
0.18±0.10 |
0.001b*
|
|
Streptococcus (%) |
0.07±0.05 |
0.12±0.12 |
0.122a
|
|
Desulfovibrio (%) |
0.13±0.18 |
0.08±0.13 |
0.506a
|
|
Streptophyta (%) |
0.46±0.26 |
0.10±0.27 |
0.001a*
|
|
Porphyromonas (%) |
0.01±0.02 |
0.03±0.02 |
0.008a*
|
|
Other (%) |
86.37±9.40 |
59.61±14.65 |
0.001a*
|
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- Dynamics of the microbiota in right-sided colon cancer patients: pre- and post-tumor resection
Youn Young Park
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