Characteristics of gut microbiota dysbiosis in patients with colorectal polyps

Abstract

This editorial, inspired by a recent study published in the World Journal of Gastrointestinal Oncology, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of Klebsiella, Parvimonas, and Clostridium increase, while those of Bifidobacterium and Lactobacillus decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.

Key Words: Recurrent colorectal polyps; Gut microbiota dysbiosis; Klebsiella; Probiotics; Intestinal inflammation; Microbial intervention strategy

Core Tip: This review addresses gut microbiota dysbiosis in patients with recurrent colorectal polyps, noting increased levels of Klebsiella, Parvimonas, and Clostridium and decreased levels of Bifidobacterium and Lactobacillus. This dysbiosis may promote polyp formation and recurrence by creating an inflammatory gut environment. A reduction in probiotics weakens intestinal barrier function, while an increase in pathogens further degrades the gut through their metabolic products and toxins. These changes are also observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome. Regulating the gut microbiota, particularly by increasing the use of probiotics, may restore gut health and prevent polyp recurrence. Future research should explore specific mechanisms and evaluate long-term effects.

INTRODUCTION

Recurrent colorectal polyps are a key precursor to the development of colorectal cancer, the second leading cause of cancer-related deaths worldwide[1]. Adenomatous polyps (APs) are the most common precancerous lesions of colorectal cancer, with a recurrence rate of 20%–50%[2]. Studies have shown that gut microbiota dysbiosis plays an important role in the formation and recurrence of polyps[3]. Dysbiosis is characterized by a decrease in beneficial bacteria such as Bifidobacterium and Lactobacillus and an increase in pathogenic bacteria such as Klebsiella, Sutterella, and Cronobacter[4]. This increase in pathogenic bacteria may promote the formation and recurrence of polyps by fostering an inflammatory environment in the gut[5]. Additionally, changes in the gut microbiota are associated not only with polyp recurrence but also with colorectal cancer, inflammatory bowel disease (IBD), autism spectrum disorder (ASD), and metabolic syndrome[6]. Regulating the gut microbiota, particularly by increasing the levels of probiotics and reducing the abundance of pathogenic bacteria, may help prevent polyp recurrence and promote gut health[7]. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps, and further research will help determine its efficacy and underlying mechanisms[8].

MICROBIOTA CHANGES IN DIFFERENT DISEASES

The formation of recurrent colorectal polyps is closely related to intestinal dysbiosis, which involves not only changes in the composition of the gut microbiota but also alterations in metabolic products and the significance of the gut under physiological and pathological conditions. The gut plays a critical role in maintaining overall health, with its barrier function, immune regulation, metabolic activities, and connections to neurological and psychological health exerting significant influence under both normal and pathological states[9]. The physical barrier formed by intestinal epithelial cells and the mucosal immune system represents the first line of defense against pathogenic invasion and maintains systemic homeostasis. When intestinal barrier function is compromised, as observed in IBD, increased intestinal permeability may trigger systemic inflammation, exacerbating disease progression[10]. Moreover, the gut microbiota plays a key role in host metabolism and immune regulation, with the production of short-chain fatty acids (SCFAs) providing energy to the intestinal epithelium, exerting anti-inflammatory effects, and protecting the barrier[11]. Certain probiotics, such as Bifidobacterium and Lactobacillus, can inhibit inflammatory responses and maintain immune homeostasis in the gut by modulating the T-cell balance[12]. Furthermore, the bidirectional communication between the gut and brain, known as the gut-brain axis, highlights the impact of the gut microbiota on neurological and psychological health. For example, dysbiosis observed in patients with ASD may affect behavior and cognitive function through the gut-brain axis[13]. Patients with metabolic syndrome exhibit significant changes in the gut microbiota, such as a decrease in beneficial bacteria and an increase in pathogenic bacteria, which are closely associated with insulin resistance and lipid metabolism abnormalities[14]. Similar dysbiosis plays a crucial role in diseases such as obesity and colorectal cancer, affecting energy metabolism and the inflammatory status[15]. Research suggests that certain pathogenic bacteria, such as Escherichia coli and Klebsiella, can produce genotoxic substances that promote the development of colorectal cancer[16]. Modulating the gut microbiota, particularly by increasing the use of probiotics and prebiotics, may have potential in the prevention and treatment of colorectal cancer and other related diseases[17]. The impact of gut dysbiosis extends beyond individual gut health and may influence overall systemic health through complex biochemical pathways, which is particularly evident in the pathological process of colorectal polyps and their recurrence[18]. Therefore, further exploration of changes in the gut microbiota in various diseases not only aids in understanding the pathogenesis of these conditions but also provides new directions for clinical interventions. Studies have shown that the following bacterial groups are significantly associated with recurrent colorectal polyps: Klebsiella, Sutterella, Cronobacter, Bifidobacterium, and Lactobacillus. Klebsiella is a gram-negative bacterium that is commonly associated with intestinal infections and antibiotic resistance. In patients with non APs or APs, the abundance of this bacterium is significantly increased, which may be one of the key factors in gut microbiota dysbiosis. These findings suggest that Klebsiella plays a potential role in the formation and recurrence of polyps[19]. Sutterella is also a gram-negative bacterium associated with intestinal inflammation and diseases. Studies have shown that the abundance of this bacterium is significantly greater in polyp patients than in healthy individuals, especially in patients with recurrent polyps. These findings indicate that Sutterella may play a role in polyp recurrence by promoting the formation of an inflammatory environment in the gut, further supporting this conclusion[20]. Cronobacter is another gram-negative bacterium that is known to be associated with foodborne diseases and infections. In polyp patients, particularly those with Aps, the abundance of Cronobacter is significantly increased. The increase in this bacterium may be related to the formation and development of polyps, suggesting its role in gut microbiota dysbiosis[21]. Bifidobacterium and Lactobacillus are two common probiotics that are generally beneficial for gut health. However, in all types of polyp patients, the levels of these two probiotics are reduced. The decrease in Bifidobacterium levels may be associated with the formation and recurrence of polyps, while the reduction in Lactobacillus further supports the role of gut microbiota dysbiosis in polyp formation[22]. A decrease in probiotic levels may weaken intestinal barrier function and increase gut inflammation, thereby promoting the formation and recurrence of polyps. These bacterial groups are closely related to gut microbiota dysbiosis and recurrent colorectal polyps. Increasing the levels of probiotics and targeting specific pathogenic bacteria may help prevent polyp recurrence and promote gut health. In addition, these bacterial groups are closely related to other diseases in the body. Table 1 below details the changes in the microbiota in different diseases[23-27].

Table 1 Relationship between gut microbiota and colorectal polyps.

Disease/microbiota	Bifidobacterium	Lactobacillus	Klebsiella	Sutterella	Cronobacter	Ref.
Colorectal cancer	Decrease	Decrease	Increase	Increase	Increase	[23,24]
Inflammatory bowel disease	Decrease	Decrease	Increase	Increase	Increase	[25]
Autism spectrum disorder	Decrease	Decrease	Increase	Increase	Increase	[26]
Metabolic syndrome	Decrease	Decrease	Increase	Increase	Increase	[27]

Colorectal cancer

Colorectal cancer is a common malignant tumor, with symptoms including abdominal pain, bloody stools, weight loss, and bowel dysfunction. Changes in the microbiota are characterized by a decrease in the abundance of probiotics such as Bifidobacterium and Lactobacillus and an increase in the abundance of pathogenic bacteria such as Klebsiella, Sutterella, and Cronobacter[28]. This dysbiosis may promote intestinal inflammation and the development and progression of cancer.

IBD

IBD includes Crohn's disease and ulcerative colitis, characterized by chronic intestinal inflammation. Symptoms include abdominal pain, diarrhea, weight loss, and fatigue. Studies have shown that the levels of Bifidobacterium and Lactobacillus decrease in IBD patients, while the levels of Klebsiella, Sutterella, and Cronobacter increase. These changes in the microbiota may lead to weakened intestinal barrier function and persistent inflammation[29].

ASD

ASD is a neurodevelopmental disorder characterized by impaired social communication, repetitive behaviors, and restricted interests. The gut microbiota of individuals with autism shows a decrease in Bifidobacterium and Lactobacillus and an increase in Klebsiella, Sutterella, and Cronobacter. These changes may be associated with intestinal dysfunction and systemic inflammation[30].

Metabolic syndrome

Metabolic syndrome includes hypertension, high blood sugar, excess abdominal fat, and abnormal cholesterol or triglyceride levels, increasing the risk of heart disease, stroke, and diabetes. In patients with metabolic syndrome, the levels of Bifidobacterium and Lactobacillus decrease, while the levels of Klebsiella, Sutterella, and Cronobacter increase. This dysbiosis may lead to increased intestinal permeability and systemic inflammation[31].

MICROBIOTA CHANGES IN DIFFERENT TYPES OF POLYPS

Studies have shown that changes in the gut microbiota in different diseases significantly impact health. In patients with colorectal cancer, the abundances of Klebsiella, Sutterella, and Cronobacter significantly increase, while those of Bifidobacterium and Lactobacillus significantly decrease[32]. This dysbiosis pattern is also observed in patients with IBD and ASD[33]. These changes suggest that the increase in pathogenic bacteria and the decrease in probiotics may promote intestinal inflammation and disease progression. Specifically, in colorectal polyps, there are significant differences in the gut microbiota composition between polyp patients and healthy individuals. The levels of Bifidobacterium and Lactobacillus are relatively higher and the levels of Klebsiella, Sutterella, and Cronobacter are relatively lower in the gut of healthy individuals, helping to maintain intestinal balance and health[34]. In contrast, the levels of Bifidobacterium and Lactobacillus are significantly lower, while the levels of Klebsiella, Sutterella, and Cronobacter are significantly higher in the gut of healthy individuals. This dysbiosis may deteriorate the intestinal environment, promoting the formation and development of polyps[35]. Even in patients who have previously had adenomas but currently have no adenomas, their gut microbiota has not fully returned to normal, showing changes similar to those in non adenomatous and APs patients. These findings suggest that targeted regulation of the gut microbiota, particularly by increasing probiotic levels and reducing the abundance of pathogenic bacteria, may help prevent polyp recurrence and promote gut health. Further studies also indicate that dysbiosis is reflected not only in the composition of the microbiota but also in the levels of metabolites. Changes in metabolites in patients with colorectal polyps include a decrease in SCFAs, such as butyrate and propionate, and an increase in amine metabolites and bile acids, which may further promote inflammation and the development of polyps. Table 2 provides a detailed description of the microbiota changes in patients with different types of colorectal polyps and healthy individuals. In healthy individuals, the gut contains high levels of probiotics (such as Bifidobacterium and Lactobacillus) and low levels of pathogenic bacteria. This balance helps maintain gut health and immune function. However, in non APs patients, probiotic levels significantly decrease, while pathogenic bacteria, especially Klebsiella, Sutterella, and Cronobacter, increase. The increase in these pathogenic bacteria may be associated with intestinal inflammation and polyp formation[36-41]. The situation in APs patients is similar to that in non APs patients, with a significant reduction in probiotic levels and an increase in pathogenic bacteria. This dysbiosis is considered an important factor in the formation and development of adenomas[42]. Studies have shown that the gut microbiota also shows similar characteristics in patients who have previously had adenomas, with decreased probiotics and increased pathogenic bacteria[43]. These changes indicate that gut microbiota dysbiosis is a significant risk factor for colorectal polyps, especially recurrent APs. Restoring probiotic levels and targeting specific pathogenic bacteria may become important strategies for preventing polyp recurrence[42,43]. By regulating the gut microbiota, particularly by increasing the abundance of probiotics such as Bifidobacterium and Lactobacillus, it is possible to help restore normal gut function, reduce inflammation, and thus lower the recurrence rate of polyps[44]. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps, and further research will help determine its efficacy and underlying mechanisms[41]. Studies have shown that different plant extracts have significant effects on regulating the gut microbiota. The extract of Salvia miltiorrhiza improves gut microbiota dysbiosis in hypertensive rats induced by a high-salt diet by regulating the Th17/Treg cell balance, significantly increasing the proportion of beneficial bacteria such as Prevotellaceae[45]. Huanglian-derived polysaccharides increase the growth of beneficial bacteria and the concentration of SCFAs, especially butyric acid, in a high-fat diet/streptozotocin-induced type 2 diabetes mouse model[46]. Phyllostachys nigra polysaccharides significantly improve the gut microbiota structure and reduce insulin resistance by regulating glucose and lipid metabolism in diabetic mice[47]. Phyllanthus emblica extract significantly alters the gut microbiota structure in high-fat diet-induced hyperlipidemic mice, increasing the proportion of specific probiotics, such as Akkermansia and Bacteroides, while reducing harmful bacteria and lowering SCFA levels[48]. These findings suggest that by balancing the gut microbiota, the symptoms of related diseases can be effectively improved, indicating potential therapeutic effects on gut microbiota dysbiosis in patients with colorectal polyps.

Table 2 Changes in microbiota in patients with different types of colorectal polyps and healthy individuals.

Microbiota/disease state	Healthy individuals	Non-adenomatous polyp patients	Adenomatous polyp patients	Previous adenoma patients (currently no adenoma)	Ref.
Bifidobacterium	High	Decreased	Decreased	Decreased	[36]
Lactobacillus	High	Decreased	Decreased	Decreased	[37]
Klebsiella	Low	Increased	Increased	Increased	[38]
Sutterella	Low	Increased	Increased	Increased	[39]
Cronobacter	Low	Increased	Increased	Increased	[40]

METABOLITE CHANGES

Studies have shown that gut microbiota dysbiosis manifests not only in microbial composition but also in significant differences in metabolite levels. Changes in metabolites in colorectal polyp patients are particularly prominent and involve key metabolites such as SCFAs, vitamin synthesis metabolites, bile acids, and amine metabolites. Specifically, in the gut of healthy individuals, the levels of SCFAs such as butyrate and propionate are high, and these metabolites play important roles in maintaining gut health and reducing inflammation. However, in non APs and APs patients, the levels of butyrate and propionate significantly decrease, indicating weakened anti-inflammatory and barrier functions of the gut[49-51]. Additionally, the levels of bile acids such as deoxycholic acid significantly increase in polyp patients, further promoting the formation of an inflammatory environment in the gut. This change is particularly evident in APs patients. In contrast, patients who previously had adenomas but currently have no adenomas have partially restored normal metabolite levels, but their bile acid and amine metabolite levels are still higher than those of healthy individuals, suggesting long-term effects of dysbiosis[49-51]. Amine metabolites such as cadaverine and histamine also increase in polyp patients, further exacerbating the pathological state of the gut[52]. In summary, these changes in metabolites not only deepen our understanding of the role of gut microbiota dysbiosis in polyp formation but also provide new directions for future prevention and treatment strategies. The following table details the changes in metabolites in patients with different types of colorectal polyps and in healthy individuals. These changes indicate that dysbiosis is reflected not only in the composition of the microbiota but also in significant differences in metabolite levels. Changes in metabolites in colorectal polyp patients include decreases in SCFAs such as butyrate and propionate and increases in amine metabolites and bile acids. These changes may further promote inflammation and the development of polyps. Specifically, butyrate and propionate levels are increased in healthy individuals. Table 3 provides a detailed description of the metabolite changes in patients with different types of colorectal polyps and healthy individuals. These changes indicate that dysbiosis is reflected not only in the composition of the microbiota but also in significant differences in metabolite levels. Changes in metabolites in colorectal polyp patients include decreases in SCFAs such as butyrate and propionate and increases in amine metabolites and bile acids. These changes may further promote inflammation and the development of polyps. Specifically, butyrate and propionate levels are increased in healthy individuals, and these metabolites help maintain gut health and reduce inflammation[53-56]. However, in non APs and APs patients, butyrate and propionate levels are significantly decreased, indicating a weakened intestinal barrier function and anti-inflammatory capacity[57,58]. Additionally, the levels of deoxycholic acid and amine metabolites in these patients increase, further exacerbating intestinal inflammation and the development of polyps[59]. Even in patients who previously had adenomas but currently have no adenomas, their metabolite levels have not fully returned to normal, showing changes similar to those in non adenomatous and APs patients. These findings suggest that the impact of dysbiosis may be long-term and that restoring normal microbiota and metabolite levels may require more time[60]. Overall, these findings emphasize the importance of targeted regulation of the gut microbiota and metabolites. Increasing the levels of probiotics such as Bifidobacterium and Lactobacillus, reducing the abundance of pathogenic bacteria such as Klebsiella, Sutterella, and Cronobacter, and restoring the levels of SCFAs while reducing harmful metabolites may help prevent the recurrence of colorectal polyps and promote overall gut health.

Table 3 Metabolite changes in patients with different types of colorectal polyps and healthy individuals.

Metabolites/disease state	Healthy individuals	Non-adenomatous polyp patients	Adenomatous polyp patients	Previous adenoma patients (currently no adenoma)	Ref.
SCFAs
Butyrate	High	Significantly decreased	Significantly decreased	Restored to near normal levels, but lower than healthy individuals	[53]
Propionate	High	decreased	Decreased	Partially restored, but still lower than healthy individuals	[53]
Vitamin synthesis metabolites
Vitamin B complex	High	No significant change	No significant change	No significant change	[54]
Bile acids
Deoxycholic acid	Normal levels	Increased	Significantly Increased	Partially restored, but still higher than healthy individuals	[55]
Amine metabolites
Cadaverine, histamine	Normal levels	No significant change	Increased	Decreased, but still higher than healthy individuals	[56]

SCFAs: Short-chain fatty acids.

This study investigated the characteristics of gut microbiota dysbiosis in patients with recurrent colorectal polyps and further analyzed the broad impact of this dysbiosis on other systemic diseases. The results demonstrate that the gut microbiota plays a crucial role in host health and the development of various diseases. Specifically, gut dysbiosis is not only significant in digestive system diseases but also has far-reaching effects on multiple conditions, including ASD, metabolic syndrome, and neurodegenerative diseases. These findings provide new perspectives on the relationship between the gut microbiota and various diseases and offer important references for future clinical treatment strategies. In patients with recurrent colorectal polyps, gut dysbiosis is characterized by a significant increase in pathogenic bacteria abundance and a marked decrease in probiotic levels. This dysbiosis may promote the formation and recurrence of polyps through multiple mechanisms. The overgrowth of pathogenic bacteria, such as Klebsiella and Clostridium species, can disrupt intestinal barrier function, leading to local inflammatory responses. This inflammatory response not only directly damages intestinal epithelial cells but also promotes polyp growth and increases the risk of carcinogenesis by inducing a chronic inflammatory environment[61,62]. Additionally, the metabolic products of the gut microbiota play crucial roles in regulating the tumor microenvironment. For example, SCFAs produced by certain pathogenic bacteria can regulate host immune responses and directly participate in polyp formation and progression by influencing gene expression in intestinal epithelial cells[63]. However, the impact of gut dysbiosis extends far beyond colorectal polyps or other digestive system diseases. In recent years, increasing research has revealed the central role of the gut microbiota in various systemic diseases. Particularly in ASD, patients often exhibit significant gut microbiota dysbiosis, which is closely related to their neurobehavioral abnormalities. Patients with ASD exhibit a significantly reduced gut microbiota diversity, a general decrease in probiotic levels, and an increased abundance of potential pathogens such as Clostridium and Bacteroides species. This dysbiosis is not only associated with digestive system symptoms but may also affect central nervous system function through the “gut-brain axis”, contributing to the core symptoms of ASD, such as social deficits and behavioral abnormalities[64,65]. Specifically, studies suggest that a reduction in SCFA levels in ASD patients may exacerbate neuroinflammation, which is a significant factor leading to cognitive impairment in these patients[66]. In metabolic syndrome, the impact of gut dysbiosis is profound. Metabolic syndrome involves obesity, diabetes, and cardiovascular diseases, and it has a complex pathogenesis. Research shows that the ratio of Firmicutes to Bacteroidetes is significantly imbalanced in the gut of obese patients, leading to increased energy intake efficiency and fat storage[67]. This dysbiosis may also trigger systemic inflammatory responses by increasing intestinal permeability, further exacerbating the symptoms of metabolic syndrome[68]. Even with lifestyle interventions such as dietary control or exercise, these gut microbiota characteristics may persist long-term in patients, indicating the long-term role of the gut microbiota in metabolic syndrome[69]. The role of gut dysbiosis in neurodegenerative diseases has also garnered significant attention in recent years. Patients with Alzheimer's disease and Parkinson's disease exhibit significantly reduced gut microbiota diversity, along with the proliferation of pathogenic bacteria and a decrease in probiotics. Gut dysbiosis may affect central nervous system health through multiple pathways. It may disrupt the blood-brain barrier, increasing the likelihood of harmful metabolites such as lipopolysaccharides entering the brain, thereby triggering neuroinflammation[70,71]. Chronic inflammation in the gut caused by dysbiosis may further affect brain neuron function through systemic circulation, ultimately exacerbating the progression of neurodegenerative diseases[72]. These findings underscore the central role of the gut microbiota in host health. Gut dysbiosis not only affects the digestive system but also influences overall health through complex biochemical signaling pathways. The chronic inflammation and metabolic disorders triggered by gut dysbiosis not only exacerbate disease progression but also may play a critical role in the early stages of disease onset. Therefore, targeted interventions that modulate the gut microbiota, such as probiotic supplementation, prebiotic application, or fecal microbiota transplantation, may offer new strategies for preventing and treating various diseases. However, the long-term effects and safety of these interventions need to be validated through larger-scale clinical studies.

CONCLUSION

Studies have shown that gut microbiota dysbiosis is a significant characteristic in patients with recurrent colorectal polyps. Specifically, the abundances of Klebsiella, Sutterella, and Cronobacter increase, while those of Bifidobacterium and Lactobacillus significantly decrease. This dysbiosis may promote the formation and recurrence of polyps by fostering an inflammatory environment in the gut. In the gut of colorectal polyp patients, a reduction in probiotics such as Bifidobacterium and Lactobacillus weakens intestinal barrier function, leading to increased inflammatory responses in the gut. Conversely, the increase in pathogenic bacteria such as Klebsiella, Sutterella, and Cronobacter may further deteriorate the gut environment through their metabolic products and toxic factors, promoting the growth and recurrence of polyps. Similar changes in the microbiota have also been observed in patients with colorectal cancer, IBD, ASD, and metabolic syndrome. The increase in pathogenic bacteria and decrease in probiotics in these diseases further support the important role of dysbiosis in disease progression. Specifically, Klebsiella is associated with intestinal infections and antibiotic resistance, Sutterella is closely linked to intestinal inflammation and diseases, and Cronobacter is known to be associated with foodborne diseases and infections. Future research should further explore the specific mechanisms of the gut microbiota and metabolites, develop personalized microbial intervention plans, and evaluate the long-term effects of gut microbiota regulation on the prevention of polyp recurrence. These studies will provide more effective prevention and treatment strategies for clinical practice and will further advance the treatment of colorectal polyps and related diseases. Regulating the gut microbiota, particularly by increasing the levels of probiotics such as Bifidobacterium and Lactobacillus, may help restore gut health and prevent the recurrence of polyps. This microbial intervention strategy holds potential not only for patients with colorectal polyps but also for the treatment of other related diseases. In summary, regulating the gut microbiota and restoring a healthy balance are key strategies for the prevention and treatment of colorectal polyps and related diseases.