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Colorectal cancer, gut microbiota, Escherichia coli, dysbiosis, Proteobacteria
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Pino Z, Parewangi L, Rasyid H et al. Microbiota Profiles of Cancer Tissue, Normal Mucosal Tissue, and Feces in Colorectal Cancer at Wahidin Sudirohusodo Hospital [version 1; peer review: 1 approved with reservations]. F1000Research 2026, 15:638 (https://doi.org/10.12688/f1000research.178918.1)
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Research Article
Microbiota Profiles of Cancer Tissue, Normal Mucosal Tissue, and Feces in Colorectal Cancer at Wahidin Sudirohusodo Hospital
[version 1; peer review: 1 approved with reservations]
PUBLISHED 29 Apr 2026
OPEN PEER REVIEW
REVIEWER STATUS
This article is included in the Oncology gateway.
Abstract
Corresponding author:
Zuriyatina Pino
Competing interests:
No competing interests were disclosed.
Grant information:
The author(s) declared that no grants were involved in supporting this work.
Copyright:
© 2026 Pino Z et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Pino Z, Parewangi L, Rasyid H et al. Microbiota Profiles of Cancer Tissue, Normal Mucosal Tissue, and Feces in Colorectal Cancer at Wahidin Sudirohusodo Hospital [version 1; peer review: 1 approved with reservations]. F1000Research 2026, 15:638 (https://doi.org/10.12688/f1000research.178918.1)
First published: 29 Apr 2026, 15:638 (https://doi.org/10.12688/f1000research.178918.1)
Latest published: 29 Apr 2026, 15:638 (https://doi.org/10.12688/f1000research.178918.1)
Introduction
Colorectal cancer is a malignancy of the gastrointestinal tract that arises from abnormal epithelial growth (neoplasia) in the colon. It is among the most common cancers: in the United States, it is the third most frequently diagnosed cancer in both men and women, and in 2020 the IARC GLOBOCAN (WHO) database also ranked colorectal cancer as the third most common cancer worldwide. In general, colorectal cancer predominantly affects older adults, but its incidence has been increasing in younger populations. Between 2007 and 2016, incidence rates decreased by 3.6% per year in adults aged >55 years, yet increased by 2% per year in adults aged <55 years. Colon carcinogenesis results from interactions between environmental and genetic factors, multiple environmental exposures can act alongside inherited predisposition or acquired defects to drive carcinogenesis.1,2
According to WHO, risk factors include age > 50 years, polyposis syndromes (familial adenomatous polyposis, hamartomatous polyposis, and Peutz–Jeghers syndrome), a family history of colorectal cancer, inflammatory bowel disease, a personal history of colorectal cancer, and a history of colorectal polyps. Because only about 10–15% of cases are hereditary, environmental factors play a major role in influencing colorectal cancer development through genetic and epigenetic mechanisms. Over the past two decades, colorectal cancer has increasingly been diagnosed in individuals aged <50 years, a condition referred to as early-onset colorectal cancer (EOCRC). The rise in EOCRC is thought to be associated with generational shifts toward higher body mass index (BMI) and obesity due to early-life exposure to carcinogenic factors, interactions between the gut microbiota and inflammation, and other external factors such as poor-quality diets (red/processed meat, ultra-processed foods, high saturated fat and sugar, low fiber, and high salt/preservatives and additives).3–5
Recent studies have increasingly highlighted the relationship between colorectal cancer and the gut microbiota. The gastrointestinal tract is colonized by approximately 1013 sampai 1014 microorganisms and contains more than 3 million microbial genes, in adults, it comprises over 1,000 species and more than 7,000 bacterial strains. The gut microbiota plays an essential role in maintaining intestinal homeostasis, including immune function, metabolism, and mucosal integrity. The four dominant bacterial phyla are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Alterations in microbial diversity and composition such as loss of beneficial microbes or overgrowth of harmful species are termed dysbiosis, and this condition has been associated with various gastrointestinal diseases, including colorectal cancer.5–9
The gut microbiota profile in colorectal cancer differs from that of a normal intestine. Bacteria commonly associated with colorectal cancer include Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis. Kim J et al. (2021) reported a predominance of opportunistic anaerobes and enteric pathogens particularly F. nucleatum, enterotoxigenic B. fragilis, and E. coli which are thought to contribute to colorectal carcinogenesis through chronic inflammation, biofilm formation, disruption of the epithelial barrier, and DNA damage. Zhong et al. (2023), using 16S rRNA sequencing, found that normal colon/rectal mucosa is dominated by mucosa-associated microbiota, with commonly detected genera such as Fusobacterium, Haemophilus, Streptococcus, Escherichia/Shigella, and Veillonella (which may represent physiological colonizers but can contribute to inflammation and carcinogenesis under certain conditions). Colorectal cancer tissue is likewise dominated by mucosa-associated microbiota especially Fusobacterium, Escherichia/Shigella, Streptococcus, Haemophilus, and Veillonella reflecting dysbiosis. In contrast, fecal microbiota more strongly represent luminal bacteria involved in nutrient metabolism and short-chain fatty acid (SCFA) production, such as Bacteroides, Prevotella, Faecalibacterium, Blautia, Ruminococcus, Subdoligranulum, and Roseburia.10
Artem et al. (2022) reported that normal colonic mucosa is enriched with SCFA-producing commensal bacteria, such as Faecalibacterium, Roseburia, Bifidobacterium, Lactobacillus, and Ruminococcus. In contrast, colorectal cancer tissue is more often dominated by pro-inflammatory and pro-carcinogenic bacteria, including Fusobacterium, Escherichia coli, Bacteroides fragilis, Peptostreptococcus anaerobius, and Streptococcus gallolyticus, meanwhile, fecal samples mainly reflect luminal microbial communities. Lichtenstern et al. (2023) emphasized that dysbiosis can allow pathogenic bacteria to penetrate the intestinal epithelium, leading to chronic inflammation and biofilm formation. Mucosal biofilms are more frequently found in colorectal cancer patients and may create a pro-carcinogenic microenvironment. The study also highlighted a synergistic effect of coinfection by enterotoxigenic Bacteroides fragilis (ETBF) and pks + Escherichia coli within biofilms, animal models show that coinfection increases tumor burden, worsens mucosal inflammation, causes greater DNA damage, and reduces survival compared with single infections.11
Karam F et al. (2025) concluded that dysbiosis in colorectal cancer differs clearly across tumor tissue, normal mucosa, and feces. Tumor tissue tends to show increased opportunistic anaerobes and pathogens (for example Fusobacterium nucleatum, ETBF, Peptostreptococcus anaerobius, Parvimonas micra, and colibactin-producing Escherichia coli) that promote chronic inflammation, biofilm development, impaired epithelial integrity, and DNA damage. Conversely, normal mucosa and feces are more enriched with protective SCFA-producing commensals such as Faecalibacterium prausnitzii, Roseburia species, and Eubacterium rectale. In colorectal cancer patients, these protective taxa are significantly reduced alongside an increase in pro-inflammatory and genotoxic bacteria.12,13
Based on these variations in microbiota changes associated with colorectal cancer, this study was conducted to describe the microbiota present in tumor tissue, normal mucosal tissue, and fecal samples of colorectal cancer patients at Wahidin Sudirohusodo Hospital.
Method
This study used a descriptive observational design and was conducted from October 2024 until the required sample size was achieved. All laboratory procedures were performed at the Microbiology Laboratory/HUMRC, 6th Floor, RSP FK Unhas, Makassar. The study population comprised inpatients and outpatients with confirmed colorectal cancer treated at Wahidin Sudirohusodo Hospital starting from August 2024. Participants were recruited using consecutive sampling, whereby all eligible subjects were enrolled until the target number was met. Inclusion criteria were age > 18 years, a diagnosis of colorectal cancer confirmed by histopathology, and willingness to participate until study completion. Exclusion criteria included metastatic disease, other gastrointestinal disorders, use of a colostomy bag, history of chemotherapy or radiotherapy, and antibiotic use within 30 days prior to enrollment. The minimum required number of subjects was 15, calculated using a two-proportion sample size formula (p1 = 0.53; p2 = 0.19; α = 0.05; β = 0.20). Three specimen types were collected from each participant: normal colonic mucosal tissue, colorectal cancer tissue, and fecal samples, yielding a total of 60 specimens. Microbiota profiling was performed by isolating DNA from biopsy and fecal specimens using a DNA isolation kit, followed by PCR amplification and 16S rRNA gene sequencing targeting the V3 and V5 regions to identify dominant taxa. Data were analyzed descriptively and presented as a narrative supported by tables. Ethical approval was obtained from the Biomedical Research Ethics Committee of the Faculty of Medicine, Hasanuddin University, Makassar, and written informed consent was secured after explaining the study background, objectives, benefits, and sampling procedures to all participants.
Results
1. Characteristic of correspondent
A total of 20 colorectal cancer patients were included in this study ( Table 1). The age distribution showed a balanced proportion between the <60 years and ≥60 years groups, with 10 patients (50%) in each group. Based on gender, the number of male and female respondents was also balanced, with 10 patients (50%) in each group. Nutritional status was dominated by the normal category (14 patients; 70%), followed by underweight (3 patients; 15%), obese (2 patients; 10%), and overweight (1 patient; 5%).
2. Tumor location
The most common tumor location was the rectosigmoid, found in 16 patients (80%). Other locations were less common, namely the descending colon in 2 patients (10%), the ascending colon/cecum in 1 patient (5%), and the transverse colon in 1 patient (5%) ( Table 1).
3. Microbiota distribution by species
A comparison of microbiota species in cancer tissue, normal mucosal tissue, and feces is shown in Table 2 (n = 20 each). Overall, Escherichia coli was the most frequently found species in all three types of samples, with the highest proportion in cancer tissue (8/20; 40%), compared to normal mucosal tissue (6/20; 30%) and feces (6/20; 30%).
Table 2. Comparison of species in cancer tissue, normal mucosal tissue, and fecal samples in patients with colorectal cancer.
In cancerous tissue, besides Escherichia coli, other bacterial species detected included Bacteroides fragilis (2/20; 10%), and each of the following at 1/20 (5%): Shigella sp., Shigella sonnei, Salmonella enterica, Pseudomonas sp., Bacteroides graminisolvens, and Aeromonas sp. No bacterial growth was observed in 4 of the cancer tissue samples (20%).
In normal mucosal tissue, aside from E. coli (30%), the species detected were B. fragilis (2/20; 10%), Salmonella enterica (2/20; 10%), and Enterobacter sp. (2/20; 10%). Species found in 1/20 (5%) of samples included Escherichia fergusonii, Klebsiella pneumoniae, Bacillus subtilis, Microbacterium paraoxydans, and Staphylococcus sp. There was no bacterial growth in 3 of the normal mucosa samples (15%).
In fecal samples, E. coli remained the most frequently detected organism (6/20; 30%), followed by Klebsiella pneumoniae (4/20; 20%), B. fragilis (3/20; 15%), and Faecalibacterium prausnitzii (2/20; 10%). Other species detected at 1/20 (5%) included Shigella sp., Shigella sonnei, Corynebacterium sp., and Oscillospiraceae bacterium. Additionally, one fecal sample showed no bacterial growth (5%).
4. Microbiota distribution by genus
A comparison of genera in cancer tissue, normal mucosal tissue, and feces is shown in Table 3. The most dominant genus in all sample types was Escherichia, with the highest proportion in cancer tissue (8/20; 40%), followed by normal mucosal tissue (7/20; 35%) and feces (6/20; 30%).
Table 3. Comparison of Genera in cancer tissue, normal mucosal tissue, and fecal samples in patients with colorectal cancer.
In cancer tissue, besides Escherichia, other genera identified were Bacteroides (3/20; 15%) and Shigella (2/20; 10%), as well as Salmonella, Pseudomonas, and Aeromonas, each detected in 1/20 samples (5%). No bacterial growth was observed in 4 cancer tissue samples (20%).
In normal mucosal tissue, after Escherichia (35%), the genera detected were Salmonella and Enterobacter (each 2/20; 10%), Staphylococcus (2/20; 10%), and Bacteroides, Klebsiella, and Microbacterium (each 1/20; 5%). No growth was found in 3 samples (15%).
In fecal samples, Escherichia (30%) remained the most prevalent genus, followed by Klebsiella (5/20; 25%), Bacteroides (3/20; 15%), and Faecalibacterium (2/20; 10%). Other genera, each detected in 1/20 samples (5%), included Shigella, Corynebacterium, and Oscillospira, and 1 sample showed no growth (5%).
5. Microbiota distribution based on phylum
Proteobacteria was the most dominant phylum across all sample types, accounting for 13/20 (65%) in cancer tissue, 12/20 (60%) in normal mucosal tissue, and 12/20 (60%) in fecal samples. The phylum Bacteroidetes was detected at the same proportion in cancer tissue and feces (3/20; 15% each), but at a lower proportion in normal mucosal tissue (1/20; 5%). Firmicutes was not detected in cancer tissue, but was found in normal mucosal tissue (2/20; 10%) and feces (3/20; 15%). Actinobacteria was not detected in cancer tissue and was only found in normal mucosal tissue (1/20; 5%) and feces (1/20; 5%). No bacterial growth was observed in 4 cancer tissue samples (20%), 3 normal mucosal samples (15%), and 1 fecal sample (5%).
6. Proteolytic and saccharolytic microbiota groups
The classification of microbiota into proteolytic and saccharolytic groups identified by corespondent. Proteolytic microbiota were the most frequently identified across all sample types, detected in 13/20 (65%) cancer tissue samples, 14/20 (70%) normal mucosal tissue samples, and 13/20 (65%) fecal samples. Saccharolytic microbiota were less common and showed similar proportions in cancer and normal mucosal tissues (3/20; 15% each), while in fecal samples they were detected in 6/20 (15%). No growth was recorded in 4/20 (20%) cancer tissue samples, 3/20 (15%) normal mucosal samples, and 1/20 (5%) fecal samples. Overall, these findings indicate differences in microbiota patterns among cancer tissue, normal mucosa, and feces, with Escherichia predominating at the species and genus levels and Proteobacteria being the dominant phylum across all sample types ( Tables 2 and 3).
Discussion
1. Characterization of respondents
The distribution of respondents by age in this study ( Table 1) shows an equal split between individuals aged ≥60 years and <60 years, suggesting that colorectal cancer (CRC) affects both older and younger adults. This is consistent with global epidemiological trends showing a rise in CRC incidence among younger populations, particularly in high-income countries, even as rates in older groups remain high or decline due to screening efforts and lifestyle changes.
The balanced gender distribution (50% male and 50% female) aligns with existing literature indicating that while CRC risk is slightly higher in males, the difference is often not as pronounced depending on the population studied, and both sexes experience similar disease burdens in clinical cohorts. This finding supports the notion that gender alone is not a definitive risk determinant in CRC, but interacts with lifestyle, genetic, and microbiota factors.
In terms of nutritional status, most patients (70%) were classified as normal, with smaller proportions being underweight, overweight, or obese ( Table 1). Nutritional status and diet are known to influence gut microbiota composition and metabolism, which in turn can affect CRC risk. For example, a diet high in processed red meats and low in fiber has been linked to an increased abundance of pro-carcinogenic gut bacteria and secondary bile acids that promote DNA damage and inflammation, whereas fiber intake increases protective short-chain fatty acids (SCFAs) that maintain mucosal integrity.14
Taken together, the characteristics of the respondents reflect a clinically relevant CRC population and provide a basis for interpreting microbiota differences in subsequent analyses.
2. Microbiota distribution in CRC patients
The microbial species profiling revealed that Escherichia coli was the most abundant species in cancer tissues (40%), normal mucosa (30%), and feces (30%) ( Table 2). The high relative abundance of E. coli across sample types supports extensive literature demonstrating the role of specific strains of E. coli, particularly those harboring the polyketide synthase (pks) genomic island, in CRC pathogenesis. These pks-positive strains produce colibactin, a genotoxin that induces DNA damage and mutational signatures commonly observed in human CRC genomes, suggesting a causal role in tumor initiation and progression.15
Moreover, chronic interactions between colibactin-producing E. coli and epithelial cells stimulate continuous DNA damage responses and pro-inflammatory cycles that further promote carcinogenesis. The presence of E. coli in normal mucosa and feces in this study may reflect a broader state of dysbiosis that precedes or accompanies tumor development, consistent with findings that CRC-associated microbiota differ in both tumor and non-tumor tissues compared to healthy controls.14,16
Other detected species such as Bacteroides fragilis, Shigella sp., and Pseudomonas sp. in cancer tissues emphasize the complexity of microbial communities in CRC. Enterotoxigenic B. fragilis (ETBF) strains, for example, are shown to induce chronic Th17-linked inflammation and epithelial disruption through toxins like BFT, which directly activate oncogenic pathways and inflammatory cascades that promote tumor growth in animal models and human cohorts.15,17
Analysis of the genus level ( Table 3) reinforces the patterns observed at species and phylum levels, showing that Escherichia was consistently dominant across all sample types tumor tissue (40%), normal mucosa (35%), and feces (30%). The persistence of Escherichia suggests that its expansion is not limited to tumor sites but also affects surrounding tissues and fecal microbiota, indicating systemic dysbiosis rather than a local phenomenon alone. This aligns with evidence that facultative anaerobes, such as Escherichia, thrive in inflamed and oxygen-altered colonic microenvironments typical of CRC, where they can exacerbate inflammation and disrupt epithelial homeostasis.14,16
In addition to Escherichia, genera like Bacteroides and Shigella were relatively more prevalent in cancerous tissues compared to normal mucosa and feces. Bacteroides includes strains capable of producing inflammatory molecules that modulate host signaling, contributing to mucosal barrier disruption and immune activation factors associated with CRC progression.14 Although Shigella and other genera appeared at lower frequencies, their presence supports a shift toward opportunistic pathogenic bacteria in CRC patients.
Notably, Klebsiella showed higher representation in fecal samples than in tissues. Some Klebsiella species are known for eliciting pro-inflammatory responses, suggesting that fecal microbiota could reflect broader dysbiotic trends in CRC patients and might serve as a non-invasive indicator of disease-associated shifts.
Taken together, the genus distribution in Table 3 reinforces the notion that colorectal cancer is associated with a shift toward pro-inflammatory and potentially pathogenic genera, which coexist across tissue and fecal microbiomes. This pattern strengthens the hypothesis that microbial dysbiosis in CRC is systemic rather than isolated, and highlights the potential utility of genus-level profiling for diagnostic or prognostic purposes.
Proteobacteria dominance at the phylum level (65% in cancer, 60% in normal mucosa, and 60% in feces) reflects a signature pattern of microbial dysbiosis in CRC. Proteobacteria enrichment, particularly of gamma-proteobacteria such as E. coli, has been associated with inflammation, epithelial barrier disruption, and oncogenic signaling in CRC. This phylum is often considered a marker of microbial imbalance, as it tends to increase when beneficial microbes like Firmicutes decline, resulting in pro-inflammatory and pro-carcinogenic interactions within the gut ecosystem.14,18
In contrast, phyla such as Firmicutes and Bacteroidetes, which include many SCFA-producing and anti-inflammatory bacteria, are often reduced or altered in CRC. Loss of these protective bacteria can compromise mucosal integrity and immune modulation, further exacerbating tumorigenic processes.
3. Proteolytic and saccharolytic microbiota dynamics
The finding that proteolytic microbiota dominate across cancer, normal mucosa, and fecal samples suggests a shift in metabolic processes in the CRC gut environment. Proteolytic bacteria ferment amino acids and proteins into metabolites such as ammonia, hydrogen sulfide (H2S), and phenolic compounds that are associated with DNA damage, oxidative stress, and inflammation all pro-carcinogenic conditions. Conversely, saccharolytic bacteria that produce SCFAs like butyrate which has anti-inflammatory and anti-tumor effects by promoting colonocyte apoptosis and maintaining epithelial barrier function were relatively scarce in cancer tissues. Reduced SCFA production is a known feature of CRC dysbiosis and correlates with increased vulnerability to inflammation and tumor initiation (such as butyrate has been shown to have protective effects in CRC models).14,16
4. Clinical implications and future directions
The consistent patterns of microbiota alteration observed in this study highlight several translational implications:
• Microbiota as Biomarkers
The similarity of microbiota in fecal samples to CRC tissues, especially enrichment of E. coli and Proteobacteria, supports the use of fecal microbial profiling as a non-invasive diagnostic tool for CRC risk assessment and early detection, as proposed by recent microbial screening strategies.
• Therapeutic Targeting
Understanding the specific microbial signatures associated with CRC opens avenues for interventions aimed at microbiota modulation. Approaches such as probiotics, prebiotics, diet modification, and fecal microbiota transplantation could potentially restore microbial balance and reduce pro-tumorigenic influences.
• Mechanistic Insight
The presence of specific pathogenic bacteria with known molecular mechanisms (such as colibactin production, chronic inflammation induction) provides mechanistic insight into how microbial dysbiosis may contribute to the initiation and progression of CRC.
Conclusion
This descriptive observational study characterized respondent profiles and the distribution of bacterial taxa at the species, genus, and phylum levels in colorectal cancer tissue, adjacent normal colonic mucosa, and fecal samples. Across all sample types, Escherichia coli was the most frequently detected species, Escherichia was the most prevalent genus, and Proteobacteria was the dominant phylum. Microbiota classified as proteolytic predominated in cancer tissue, normal mucosa, and feces, while saccharolytic microbiota were less frequently detected. Overall, the microbiota patterns observed in tumor tissue, normal mucosa, and feces were broadly similar, with a consistent tendency toward dominance of specific taxa that are biologically relevant to colorectal cancer.
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CITE
how to cite this article
Pino Z, Parewangi L, Rasyid H et al. Microbiota Profiles of Cancer Tissue, Normal Mucosal Tissue, and Feces in Colorectal Cancer at Wahidin Sudirohusodo Hospital [version 1; peer review: 1 approved with reservations]. F1000Research 2026, 15:638 (https://doi.org/10.12688/f1000research.178918.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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PUBLISHED 29 Apr 2026
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How to cite this report:
Pangarsa EA. Reviewer Report For: Microbiota Profiles of Cancer Tissue, Normal Mucosal Tissue, and Feces in Colorectal Cancer at Wahidin Sudirohusodo Hospital [version 1; peer review: 1 approved with reservations]. F1000Research 2026, 15:638 (https://doi.org/10.5256/f1000research.197362.r482849)
The direct URL for this report is:
https://f1000research.com/articles/15-638/v1#referee-response-482849
https://f1000research.com/articles/15-638/v1#referee-response-482849
NOTE: it is important to ensure the information in square brackets after the title is included in this citation.
Reviewer Report 01 Jun 2026
Eko Adhi Pangarsa,
Diponegoro University, Dr. Kariadi General Hospital, Semarang, Indonesia
Approved with Reservations
VIEWS 6
Only 20 pts include in this study. May be too small for microbial profiling study.
This study does not include healthy people, so we cannot determine whether the taxa are truly CRC association or normal regional microbiota
Please ... Continue reading
This study does not include healthy people, so we cannot determine whether the taxa are truly CRC association or normal regional microbiota
Please ... Continue reading
CITE
HOW TO CITE THIS REPORT
Pangarsa EA. Reviewer Report For: Microbiota Profiles of Cancer Tissue, Normal Mucosal Tissue, and Feces in Colorectal Cancer at Wahidin Sudirohusodo Hospital [version 1; peer review: 1 approved with reservations]. F1000Research 2026, 15:638 (https://doi.org/10.5256/f1000research.197362.r482849)
The direct URL for this report is:
https://f1000research.com/articles/15-638/v1#referee-response-482849
https://f1000research.com/articles/15-638/v1#referee-response-482849
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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