Role of microbiota in colorectal cancer: From pathogenesis to treatment

GRAPHICAL ABSTRACT

1. Introduction

The vast collection of organisms known as microbiota, mainly located in the gut, is crucial for promoting wellness and for preventing illnesses. This diverse array of microorganisms includes bacteria, viruses, fungi, and protozoa. Beneficially engaging the body by aiding digestion, regulating the immune system, and safeguarding it against harmful pathogens. The regulation of microbiota is essential for health. However, dysbiosis disrupts the community balance. It can lead to various diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cancer (Acevedo-Román et al., 2024).

Colorectal cancer (CRC) ranks highly among the causes of morbidity and mortality linked to cancer globally and is a public health issue (Morgan et al., 2023). Globally, CRC accounts for approximately 10% of all cancer cases, with an estimated 1.9 million new cases and 935,000 deaths in 2020². CRC is the third most diagnosed cancer worldwide, with significant regional variations in incidence rates. The occurrence and fatality rates of CRC differ among regions and demographics owing to factors such as dietary habits, lifestyle choices, genetic predisposition, and environmental influences. For instance, high-income countries report higher CRC rates compared to low-income regions, largely due to differences in dietary habits, lifestyle, and access to screening (Sawicki et al., 2021; Morgan et al., 2023). Risk factors such as obesity, smoking, and genetic predisposition further contribute to the global burden of CRC (Conti et al., 2020). With the progress in screening methods and therapies, CRC remains a health challenge that calls for a more profound comprehension of its causes and the creation of new treatment approaches (Conti et al., 2020; Sawicki et al., 2021).

New studies have focused on the role of gut microbiota in causing CRC (Wong and Yu 2019). Recent findings indicate that an imbalance in gut microbes may play a role in the development of cancer by triggering inflammation and creating harmful substances that can lead to cancer (Rebersek 2021). Specifically, identified strains such as Fusobacterium nucleatum have been linked to the risk of CRC (Kasai et al., 2016; Young et al., 2021). This emphasizes the role of microbiota in cancer progression. Studies indicate that Fusobacterium nucleatum is found more frequently in cancer tissues than in healthy tissues. This connection has been linked to the stages of the disease and worse outcomes for patients (Ou et al., 2022; Cao et al., 2024).

Growing evidence on the impact of microbiota on CRC treatment is becoming increasingly apparent. Research has shown that the gut microbiota can influence the effectiveness and side effects of chemotherapy and immunotherapies, which opens up possibilities for interventions based on microbiota (Zhao et al., 2023). Microbiota-based interventions, such as FMT, have shown promising results, with some studies reporting a 30-40% improvement in treatment outcomes when combined with chemotherapy¹¹.

In addition, the intricate connection between gut bacteria and CRC has revealed the possibility of identifying and predicting disease progression. Scientists are currently investigating these patterns as indicators of early CRC spotting and are tracking their development. These indicators offer information about the disease stage and probable outcome, thus assisting in tailoring treatment strategies (Liu et al., 2023). For instance, distinct microbial configurations have been associated with the cancer stage, presenting a non-invasive approach for evaluating illness (Liu et al., 2023).

The intricate connection between microbiota and CRC underscores the significance of research and cooperation in this area. As we expand our understanding of the subject matter, it is vital to consider the differences and external factors that affect the microbiota composition. Future research will involve creating tailored therapies based on microbiota and incorporating examinations into CRC care. By utilizing the knowledge of the microbiota, we have the potential to unveil approaches to prevent the detection and treatment of cancer, which could lead to better patient outcomes and advancements in public health overall (Shi et al., 2024; Tito et al., 2024). This review aims to comprehensively examine the role of gut microbiota in CRC pathogenesis, diagnosis, and treatment, with a focus on microbial-based interventions such as probiotics, prebiotics, and FMT.

2. Methodologies used in microbiota studies

Studies included in this review were selected based on the following criteria: (1) focus on gut microbiota and CRC, (2) use of advanced sequencing technologies (e.g., 16S rRNA, metagenomics), and (3) availability of clinical or experimental data. Excluded studies were those that did not provide clear methodologies or lacked relevance to CRC pathogenesis or treatment. Knowledge of the methods utilized to study microbiota plays a role in comprehending the outcomes and their significance in cancer. Different methods have been used to examine gut microbiota, including the strengths and weaknesses of each approach.

The 16S rRNA sequencing method focuses on the 16S rRNA gene found in bacteria that have regions with variations that enable the identification of different bacterial species. The popularity of this technique stems from its cost efficiency and its ability to examine diversity in samples. Nevertheless, its drawback lies in its limited ability to distinguish closely related species and to provide insights into the functions of the microbiota (Johnson et al., 2019).

Metagenomics differs from 16S rRNA sequencing in that it entails sequencing all DNA in a sample to detect an array of microorganisms, such as bacteria and viruses, as well as fungi and protozoa (Yachida et al., 2019). This method provides a glimpse into the capabilities of microbiota by identifying genes associated with metabolic processes. Although metagenomics provides a thorough scope for analysis, it is expensive and requires bioinformatics software for data interpretation (Qureshi et al., 2023).

Metatranscriptomics involves sequencing RNA transcripts from samples to reveal details of metabolic processes and gene expression profiles within the microbial community. This method aids in understanding the behavior of the microbiota and their responses to environmental conditions. Nevertheless, metatranscriptomics is intricate, expensive, and requires top-notch RNA samples (Ojala et al., 2023).

Metabolomics focuses on examining the metabolites generated by microbiota to gain insights into processes in the gut environment. This approach can identify the metabolites associated with CRC development and offer a practical assessment of microbial functions. Nevertheless, it relies on tools such as mass spectrometry and is affected by diverse external elements, posing challenges for standardization (Terrón-Camero et al., 2022; Kong et al., 2023).

Each of these methods has its advantages and drawbacks to consider. 16S rRNA sequencing works well for exploring diversity at first glance; however, metagenomics and metatranscriptomics delve deeper into the genetic and functional capabilities of the microbial community. Metabolomics offers proof of activity but demands precise sample management and sophisticated analytical methods. When these techniques are combined strategically, a comprehensive understanding of the significance of the microbiota in CRC has emerged (Table 1).

3. The microbiota and CRC pathogenesis

Disrupted balance of microbes in the gut microbiota, known as dysbiosis, is now widely acknowledged as a player in the development of cancer. Dysbiosis is characterized by a significant shift in the Firmicutes to Bacteroidetes ratio (often <1.5:1) and a reduction in microbial diversity (Shannon index <3.0), accompanied by decreased short-chain fatty acid (SCFA) production (<5 mM) (Johnson et al., 2019; Kang et al., 2023). This disturbance can occur because of factors such as diet choice and antimicrobial use, as changes in lifestyle habits can promote the proliferation of harmful bacteria while reducing the diversity of beneficial microbes. Such an imbalance may lead to inflammation of the gut, a recognized risk factor for CRC (Zhao et al., 2023). Chronic inflammation promotes cancer growth by promoting cell growth, preventing cell death, and facilitating changes. Additionally, the inflamed environment leads to levels of oxygen and nitrogen compounds that can damage DNA and escalate cancer formation of cancer (Kim et al., 2023).

Certain types of bacteria are associated with a heightened risk of cancer. For example, Fusobacterium nucleatum and Bacteroides fragilis are frequently associated with CRC progression (Kasai et al., 2016; Young et al., 2021). One noteworthy example is Fusobacterium nucleatum, which has attracted interest for its association with CRC. This bacterium is believed to play a role in cancer development via various mechanisms. Fusobacterium nucleatum can attach to infiltrating cells and influence tumor formation by altering the immune response of the host. It triggers the release of substances and chemicals that can worsen inflammation and foster an environment conducive to tumor growth. Moreover, Fusobacterium nucleatum can suppress the function of killer cells and other immune cells. This allows cancer cells to evade detection by the system and keep growing unchecked (Ranjbar et al., 2021; Kim et al., 2023; Tong et al., 2023; Martin-Gallausiaux et al., 2024). While some studies suggest that Fusobacterium nucleatum is a key driver of CRC, others have reported conflicting findings, indicating that its role may vary depending on the patient’s genetic background and microbial community structure (Chen et al., 2020; Ranjbar et al., 2021).

Microbial by-products are essential for regulating inflammation, DNA integrity, and the growth of cancer cells. SCFAs such as butyrate are produced at levels of 10-20 mM in the colon, contributing to anti-inflammatory and anti-carcinogenic effects (Kang et al., 2023). When there is an imbalance in the gut flora, harmful substances such as bile acids and hydrogen sulfide may be produced, leading to increased inflammation and DNA damage (Shin et al., 2023). Metabolites have the potential to disturb balance within cells and contribute to changes that support the growth of cancer cells. The intricate relationship between metabolites and cells underscores the influence of gut bacteria on CRC development (Fig. 1), indicating a promising avenue for addressing these relationships through treatment approaches (Libiad et al., 2019; Kim 2021; Shin et al., 2023). In CRC patients, butyrate levels drop significantly to <5 mM, while secondary bile acids such as deoxycholic acid (DCA) increase from <1 μM in healthy individuals to >10 μM in CRC patients (Campbell et al., 2020). These changes occur progressively over weeks to months, correlating with disease progression (Sadler et al., 2020).

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Fig. 1.

Microbiota in CRC Pathogenesis. The gut microbiota plays a pivotal role in CRC initiation and progression through multiple mechanisms. Toxins and genotoxins produced by pathogenic bacteria induce DNA damage in intestinal epithelial cells (IECs), contributing to CRC development. Infections caused by harmful bacteria and their metabolic by-products activate tumor-associated myeloid cells (TAMCs), triggering inflammation that supports tumor growth. During inflammation, immune cells release ROS and reactive nitrogen species (RNS), leading to additional DNA damage and promoting CRC progression. Biofilms further contribute to CRC by activating interleukin-6 (IL-6) and its downstream effector, signal transducer and activator of transcription 3 (STAT3). Pathogenic bacteria and their virulence factors adhere to epithelial cells, promoting tumorigenesis. Key molecular players involved include STAT3 (a transcriptional activator), NF-κB (a transcription factor regulating DNA transcription), ROS and RNS (mediators of oxidative stress), cell adhesion molecules (CAMs), FadA (an adhesion factor from Fusobacterium), T cell immunoreceptor with Ig and ITIM domains (TIGIT, an immune regulatory molecule), and PCWBR22 (a protein repeat potentially involved in cell wall interactions).

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3.2 Immune modulation

The ability of the gut microbiota to influence CRC development is crucial as it affects both tumor advancement and the body’s immune response. Harmful bacteria can alter the system to create an environment conducive to tumor growth. For example​​, certain types of Fusobacterium nucleatum can hinder the function of killer cells (NK0 cells and T-cells​), weakening the body’s capacity to identify and eradicate cancer cells. This mechanism of evading the immune system enables cancer cells to grow uncontrollably and plays a role in tumor formation (Chavakis et al., 2019; Parhi et al., 2020; Serna et al., 2020). Moreover, long-term inflammation caused by infection and imbalance in gut bacteria can result in the production of inflammatory proteins such as IL-6, TNF alpha, and IL-1beta. These substances, which cause inflammation, promote DNA damage, cell growth, and blood vessel development, thereby establishing an environment conducive to the advancement of cancer (Fields et al., 2019).

However, friendly bacteria in the gut can enhance the ability of this system to combat cancer. This shows how gut microbes play a role in regulating the system. Some probiotics and friendly bacteria can trigger the production of inflammatory signaling molecules such as IL-10 and TGF beta (Mirlekar 2022). This helps maintain balance and reduce inflammation. These beneficial bacteria can also increase the performance of killer T and natural killer cells. This enhances the effectiveness of the system in locating and destroying cells. Methods that target gut bacteria to promote microbes in the body can increase the effectiveness of immunotherapy in CRC patients. Techniques such as probiotics and prebiotics, along with FMT, rebalance the microbiota to enhance the body’s immunity against tumors and enhance treatment results (Fig. 2). Gut bacteria can provide opportunities for preventing and treating CRC effectively (Vendrik et al., 2020; Wang et al., 2021).

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Fig. 2.

Therapeutic Approaches for CRC Management (a) Probiotics aid in CRC prevention and treatment through three key mechanisms. First, they strengthen gut barrier integrity by enhancing mucin production, upregulating tight junction proteins (TJPs), and promoting epithelial repair. Second, they modulate immune responses by activating dendritic cells (DCs), reducing T helper 17 (Th17) cells, increasing regulatory T (Treg) cells, and polarizing macrophages toward the anti-inflammatory M2 phenotype, thereby mitigating colonic inflammation. Third, probiotics provide colonization resistance by inhibiting pathogenic bacteria through antimicrobial peptide (AMP) secretion, lowering luminal pH, and directly interacting with pathogens. Additionally, FMT restores healthy gut microbiota and improves gut barrier function. (b) Prebiotics support CRC management by selectively promoting the growth and activity of beneficial probiotic bacteria, facilitating fermentation processes, preventing pathogen colonization, and being absorbed into the gut to exert anti-inflammatory effects. Conversely, postbiotics may specifically induce cytotoxic effects on tumor cells while protecting intestinal epithelial cells by preventing apoptosis of healthy cells.

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4. Microbiota as modifiers of CRC risk factors

Dietary and lifestyle choices, including antimicrobial use, significantly influence the composition and function of gut bacteria, thereby modulating CRC risk (Dudek-Wicher et al., 2018). Our diet, lifestyle habits, and antimicrobial use significantly influence the composition and function of the bacteria in our guts. High-fat diets increase the abundance of bile acid-producing bacteria by 2-3-fold, while fiber-rich diets enhance SCFA-producing bacteria by 1.5- 2-fold (Kiriyama and Nochi 2021). These dietary changes can alter the Firmicutes to Bacteroidetes ratio, with high-fat diets reducing it to <1.5:1 and fiber-rich diets maintaining it at >2:1 (Sánchez-Alcoholado et al., 2020). Consuming diets rich in processed meats and fats but lacking in fiber has been associated with an imbalance in gut bacteria, which can potentially spur the development of CRC. Such eating patterns can lead to an increase in bacteria that produce substances such as bile acids and hydrogen sulfide, which can trigger inflammation and the formation of cancerous cells (Dudek-Wicher et al., 2018; Chen et al., 2020; Kiriyama and Nochi 2021).

Recent studies have quantified the risk posed by eating red or processed meat and revealed that participants with the highest intake of red meat had a 30% increased risk of CRC, and those with the highest intake of processed meat had a 40% increased risk (Stern et al., 2024). Calcium from dairy products is thought to lower CRC risk by binding bile acids and free fatty acids in the colon, reducing their ability to damage epithelial cells. This action also indirectly supports a more favorable microbial environment by limiting substrates that harmful bacteria might otherwise use to produce carcinogenic metabolites. The Million Women Study, which tracked over 540,000 women for an average of 16 years, demonstrated that an additional 300 mg of calcium per day, roughly the calcium content of one cup of milk, is associated with a 17% reduction in CRC risk (Papier et al., 2025). This protective association was specific to most dairy sources (except for cheese and ice cream), underscoring the potential importance of calcium’s biochemical role in modulating both bile acid metabolism and microbial composition. Moderate to heavy alcohol consumption is associated with 1.2- to 1.5-fold increased risks of cancers of the colon and rectum compared with no alcohol consumption (Fedirko et al., 2011). Dietary fiber is fermented by colonic bacteria to produce short-chain fatty acids (SCFAs) such as butyrate. Butyrate supports colonocyte energy metabolism, helps maintain gut barrier integrity, and exerts anti-inflammatory effects. Fiber also shifts the microbial community toward beneficial bacteria. A meta-analysis reported that for every 10 g/day increase in dietary fiber intake, the risk of CRC decreased by about 10% (RR ≈ 0.90, 95% CI 0.85–0.95) (Aune et al., 2011). Diets that include plenty of fruit, vegetables, and whole grains help maintain a healthy microbiota that produces beneficial SCFAs known for their anti-inflammatory and anticarcinogenic effects. Factors such as activity and stress levels play a role in shaping the gut microbiota and can affect the risk of CRC (Sánchez-Alcoholado et al., 2020).

People with a family background of CRC or changes like those in the APC or MUTYH genes have an increased likelihood of developing the condition. For instance, certain types of bacteria can engage with pathways linked to CRC and affect tumor growth. Studies have revealed that bacteria in the gut can influence the expression of genes and epigenetic changes that can either promote or hinder cancer development in the body. It is crucial to understand how elements and the gut microbiota interact to develop customized approaches to prevent and treat CRC (Salvucci et al., 2022).

The gut microbiome is crucial for processing carcinogens and protective substances that influence the risk of cancer. Bacteria in the gut can transform nutrients from food and toxins into beneficial or harm substances (Wang et al., 2023). For example, certain gut bacteria can convert hydrocarbons (PAHs) from charred meat into compounds that can cause mutations, leading to DNA damage and cancer. Beneficial bacteria can break down fibers into SCFAs, protecting CRC by supporting the proper functioning of epithelial cells and reducing inflammation. Moreover, microbiota can affect the way chemopreventive compounds, such as polyphenols from fruits and vegetables, are metabolized, enhancing their ability to protect against CRC. The dynamic relationship between the gut microbiota and these metabolic processes highlights the importance of maintaining the microbiota to prevent CRC (Xu et al., 2023).

5. Microbiota in CRC diagnosis and prognosis

Microbial patterns are increasingly being recognized as indicators of detection and tracking. These patterns consist of levels linked to different stages of disease progression. Advancements in sequencing technologies have allowed researchers to identify microbiota compositions associated with CRC that can aid in detection efforts (Araujo et al., 2022). For example, increased levels of species such as Fusobacterium nucleatum and Bacteroides fragilis have been observed in patients compared to those who are not affected by the disease. The detection of these microorganisms in fecal or tissue samples can be used as an invasive method to detect CRC (Salvucci et al., 2022). This could potentially replace the need for procedures, such as a colonoscopy. Microbiota-based diagnostics, such as stool tests for Fusobacterium nucleatum, offer a non-invasive alternative to colonoscopy, with a sensitivity of 85% and specificity of 90% in early CRC detection (Salvucci et al., 2022). While colonoscopy remains the gold standard with a sensitivity of 95%, microbiota-based tests are more cost-effective (Rye et al., 2022).

In CRC, there is an increase in harmful bacterial levels along with a decline in beneficial bacterial populations within the gut flora. These alterations in the microbiota may mirror the influence of tumors on the gut environment and advance their growth (Wang et al., 2023). Furthermore, the variety and complexity of the gut community have been correlated with these results, where decreased microbial variety is usually linked to worse forecasts. These findings imply that microbial profiles may not only assist in identifying CRC but also offer predictive information that may influence treatment choices (Xu et al., 2023).

Microbiota-based diagnostics show promise for future healthcare applications, and it is essential to address these obstacles and constraints before they can be widely used in settings. One significant hurdle is the nature of the microbiota composition across individuals, which can be affected by factors such as diet, lifestyle, location, and genetics. This diversity makes it challenging to identify indicators of CRC (Araujo et al., 2022). Additionally, discrepancies in how samples are collected, processed, and analyzed can introduce inconsistencies in microbiota data, making it difficult to reliably replicate findings. Developing methods and creating procedures is crucial for converting microbiota studies into reliable diagnostic tools (Table 2). Furthermore, extensive validation research involving demographics is necessary to verify the practicality of microbiota-driven diagnostics and guarantee their efficacy across patient categories (Mo et al., 2020).

Gut microbiota-based diagnostics show promise as a non-invasive, cost-effective alternative for CRC screening. While colonoscopy remains the gold standard for accuracy, microbial biomarkers could improve early detection and prognosis, reducing the need for invasive procedures. Recently, there has been growing interest in using gut microbiota as a tool for diagnosing and predicting CRC. Identification of strains as indicators for early detection and disease advancement in CRC is becoming more prominent. Analysis of tissue samples from CRC patients has consistently shown the levels of Fusobacterium nucleatum and Bacteroides fragilis (Mo et al., 2020). This non-invasive approach could offer a means to detect CRC compared to screening methods, such as colonoscopies, suggesting a more comfortable option that could increase screening participation rates. These distinct microorganism patterns possess the capability to revolutionize the detection and treatment of early CRC, thereby facilitating interventions at an earlier stage (Wu et al., 2021).

Recent research has shown that the types of microbes’ present vary throughout the CRC stages. Late-stage illnesses tend to involve bacteria, with fewer helpful bacterial communities in the gut microbiome than in the earlier stages of disease progression. This shift in balance at each stage not only aligns with the advancement of the disease but can also provide valuable clues regarding a patient’s prognosis (Quan et al., 2023). For instance, a decrease in diversity often indicates poor outcomes. The analysis of profiles not only aids in diagnosis but also directs treatment decisions and predicts survival rates. Nevertheless, implementing these findings in world settings poses difficulties because of the variations in gut bacterial composition among people, which are affected by dietary habits, genetics, way of life, and location. Maintaining uniformity in the collection and analysis of samples is crucial to tackle these obstacles and establish microbiota-driven diagnostics as a reliable tool for managing CRC (Cai et al., 2023).

6. Microbiota-based therapies

The exploration of microbiota-focused treatments in trials for CRC has become increasingly popular and promising for enhancing patient recovery (Table 3). These treatments, such as probiotics and prebiotics, along with fecal microbiota transplantation (FMT), aim to improve the effectiveness of CRC treatment and minimize its effects. Rigorous clinical studies have assessed the safety and success rate of these interventions (Ting et al., 2022). For example, research exploring the efficacy of different types has revealed encouraging findings in shaping the balance of gut bacteria, decreasing inflammation, and potentially hindering tumor development. Similarly, therapies involving prebiotics that support the proliferation of microbes are undergoing trials to assess their impact on improving gut well-being and outcomes related to cancer (Selvamani et al., 2022).

A ground-breaking method, known as FMT, is currently being studied for the treatment of CRC. The idea behind FMT involves transferring matters from donors to patients with CRC to help restore balanced and diverse gut microbiota. These initial trials have shown results in reducing tumor size and enhancing the efficacy of chemotherapy treatments (Chen et al., 2023). Further research is ongoing to validate these outcomes and to develop procedures for using FMT in the treatment of patients with CRC. Moreover, FMT has been studied as a treatment to improve the effectiveness of immunotherapy and reduce the side effects of treatment.

While certain studies show positive changes, results could exist; others point out issues such as differences in how individual microbiota react and difficulties in making treatments uniform. Real-life stories and personal accounts also demonstrate the advantages of therapies based on microbiota by highlighting cases in which patients saw responses, treatment, and fewer negative effects (Hao et al., 2021). Nonetheless, these treatments are still being researched, and further comprehensive clinical trials are required to confirm their efficacy and safety. Incorporating microbiota analysis into procedures shows the potential for tailoring CRC treatment to individuals; however, it requires addressing existing obstacles and guaranteeing consistent and reliable results among various patient groups (Chen et al., 2023).

Emerging treatments that focus on balancing gut microbiota show promise in improving CRC treatment outcomes and minimizing their effects. The use of probiotics and prebiotics is gaining interest because of their capacity to rebalance gut microbiota equilibrium, reduce inflammation, and support reactions (Sánchez-Alcoholado et al., 2020). Researchers have found that probiotics introduce bacteria into the gut, enhance the gut barrier function, promote immune response modulation, and hinder the proliferation of harmful bacteria. Prebiotics support the growth of bacteria in the gut and play a role in maintaining a healthy balance that promotes anti-inflammatory and anti-cancer properties within the body. Taking probiotics and prebiotics alongside therapies such as chemotherapy and immunotherapy could potentially improve their effectiveness by optimizing gut conditions (Dasari et al., 2020).

FMT, an intriguing advancement in microbiota-focused treatments, transfers individuals’ fecal matter to CRC patients to rebalance their microbial environment within the gut system (Rye et al., 2022). Early clinical studies indicated that FMT not only enhanced the diversity of gut microbiota but also improved the effectiveness of chemotherapy and decreased tumor size in patients. Furthermore, ongoing research is being conducted on using FMT to improve the efficiency of immunotherapies, positioning it as a method for treating CRC (Rye et al., 2022). There are still obstacles to overcome when establishing uniform FMT protocols and guaranteeing reliable outcomes in patients with different backgrounds and characteristics. We anticipate that as treatments continue to progress and develop in the field landscape, they will offer tailored approaches to care that improve CRC outcomes by considering the unique microbial composition of each patient (Rye et al., 2022).

7. Clinical applications of microbiota research in CRC

The integration of studies into medical applications has shown great potential for enhancing CRC treatment. In this section, we delve into methods for screening tools and treatment strategies inspired by research findings, in addition to personalized medicine advancements, including an overview of current clinical trials and their projected effects (Rye et al., 2022).

Microbial signs discovered in microbiota studies can be used as invasive indicators for CRC screening and early detection (Chen et al., 2021). One example is stool tests that check for bacteria such as Fusobacterium nucleatum and Bacteroides fragilis, which have shown promise as detection tools (Dasari et al., 2020). These microbiome indicators can support screening techniques such as colonoscopy and provide patients with an intrusive and convenient choice. By combining indicators with screening methods, the early detection rates of CRC can be enhanced. This improvement can result in an improved prognosis and increased survival rates (Abavisani et al., 2024).

Therapies using microbiota, such as probiotics and prebiotics, are being developed to enhance cancer treatment by influencing the gut microbiota. Probiotics and prebiotics work towards rejuvenating the gut environment by fostering the growth of bacteria that can help curb inflammation and hinder tumor development. FMT, a procedure in which fecal matter from individuals is transferred to patients with cancer, has the potential to restore microbial balance and improve treatment outcomes (Merrick et al., 2020; Rye et al., 2022). The effectiveness of these treatments is currently being studied in trials, along with therapies such as chemotherapy and immunotherapy.

Customizing care for CRC involves adapting treatment strategies based on the unique gut bacterial composition of an individual. Analysis of the microbiome can offer insights into how a patient may respond to treatments and potential adverse reactions (Chen et al., 2024; Kang et al., 2024). For instance. Individuals with varied and well-balanced gut microbiota may respond to immunotherapy. As a result, fewer side effects were observed. Developing personalized therapies based on gut bacteria involves combining data with information as well as details about diet and lifestyle choices. Enhancing treatment effectiveness while reducing negative impacts (Chen et al., 2022).

8. Critical insights

The gut microbiota plays an essential role in the development, diagnosis, and treatment of CRC. An imbalance in gut microbiota, known as dysbiosis, contributes to CRC progression through chronic inflammation, genotoxicity, immune modulation, and metabolic alterations. Specific bacterial strains, including Fusobacterium nucleatum, Bacteroides fragilis, and certain Escherichia coli strains, have been implicated in CRC due to their inflammatory properties, ability to cause DNA damage, and disruption of immune responses. These bacteria interact with host cells and the immune system, creating a tumor-friendly environment that facilitates disease progression.

Dysbiosis affects CRC development through various mechanisms. Some bacteria, such as Escherichia coli, produce colibactin, a genotoxin that causes DNA damage, leading to genomic instability and cancerous mutations. Fusobacterium nucleatum promotes CRC by suppressing immune surveillance and increasing inflammation, thereby helping tumors evade immune detection. Additionally, microbial metabolites play a dual role in CRC progression; while SCFAs like butyrate have protective effects, other metabolic by-products, such as secondary bile acids and hydrogen sulfide, contribute to DNA damage and tumor growth. Biofilm formation by certain bacteria further exacerbates the problem by creating a chronic inflammatory microenvironment that promotes bacterial persistence and resistance to treatment.

The composition of gut microbiota is increasingly being studied as a potential diagnostic and prognostic tool for CRC. Microbial biomarkers, including elevated levels of Fusobacterium nucleatum, Bacteroides fragilis, and Escherichia coli, have been detected in fecal and tissue samples of CRC patients, offering a non-invasive alternative to traditional screening methods. CRC progression is often associated with a decline in microbial diversity and an enrichment of pathogenic bacteria, which could serve as prognostic indicators. Furthermore, gut microbiota influences treatment outcomes, as patients with a diverse and balanced microbiome tend to respond better to immunotherapy, chemotherapy, and other targeted therapies, while those with dysbiosis may experience reduced efficacy and increased adverse effects. Given the influence of microbiota on CRC, therapeutic interventions targeting microbial balance are being explored to complement conventional treatments. Probiotics, such as Lactobacillus and Bifidobacterium, help restore gut equilibrium, reduce inflammation, and improve gut barrier integrity. Prebiotics, which serve as nutrients for beneficial bacteria, encourage the growth of protective microbial communities. FMT is emerging as a promising intervention, restoring microbial diversity and enhancing chemotherapy efficacy. Additional strategies, including dietary interventions that promote high-fiber intake, targeting pathogenic bacteria, and disrupting biofilms, are being investigated to improve CRC treatment outcomes. Addressing gut microbiota imbalances offers a promising avenue for CRC prevention, early detection, and personalized treatment strategies.

9. Challenges and future directions

The vast possibilities of using microbiota for various purposes are exciting; however, there are challenges to overcome, such as differences in microbiota composition between individuals and the necessity of established protocols. Current limitations in microbiota research include technical challenges in sample collection and analysis, lack of standardized protocols, high costs associated with advanced sequencing technologies, and implementation barriers in clinical settings. For instance, metagenomic sequencing can cost up to US $1,000 per sample, and the lack of standardized protocols leads to variability in results (Abavisani et al., 2024). Future research should prioritize the development of microbiota-based biomarkers, standardization of protocols, design of large-scale clinical trials, and integration of artificial intelligence for data analysis. Additionally, there is a need for cost-effective technologies to make microbiota-based diagnostics and therapies accessible globally (Ting et al., 2022; Abavisani et al., 2024). Collaboration across disciplines will play a role in translating microbiota research into practical clinical applications and revolutionizing the management of CRC.

10. Conclusion

In conclusion, the gut microbiota plays a pivotal role in CRC pathogenesis, offering new avenues for prevention, diagnosis, and treatment. Future research should focus on standardizing microbiota analysis methods, validating microbial biomarkers in diverse populations, and integrating microbiota-based therapies into clinical practice. Collaborative efforts across disciplines will be essential to translate these findings into effective, personalized CRC treatments, ultimately improving patient outcomes and reducing the global burden of CRC.

Utilizing our understanding of microbiota presents an opportunity to enhance cancer CRC outcomes. Researchers are investigating patterns as non-invasive indicators for early CRC detection and prognosis as alternatives to conventional screening methods. Moreover, microbial-based treatments, such as probiotics and FMT, have the potential to boost treatment effectiveness and minimize the effects. These approaches can be customized for each patient according to their microbiota profile, resulting in personalized and efficient treatment plans. To realize the benefits of microbiota-based treatments for cancer (CRC), ongoing research and partnerships are vital requirements. Creating methods for microbiota studies will guarantee repeatable results, thereby easing the transition from research outcomes to practical clinical applications. Extensive verification studies across demographics are necessary to validate the effectiveness of microbiota-centered diagnosis and treatment options. Furthermore, cross-disciplinary teamwork involving scientists, medical practitioners, and data analysts is key to incorporating analysis into the care of CRC patients.

Microbiomes present a territory for the research and treatment of CRC​ because delving deeper into the connection between the microbiome and CRC and creating interventions can enhance the prevention, ​ diagnosis, and treatment of CRC​. Moving forward, this area offers prospects for progress in health and patient outcomes. Collaboration and standardization within this field are crucial for unlocking the full potential of microbiota-driven treatments, which could fundamentally change how CRC​ leads to patient outcomes.