Enterococcal autoprobiotics in the complex treatment of colorectal cancer patient receiving chemotherapy: Two case reports and review of literature

Abstract

BACKGROUND

According to the literature, significant disorders of gut microbiota are consistently observed in patients with colorectal cancer (CRC). Disorders of gut microbiota composition are manifesting clinically as abdominal pain, dyspeptic symptoms (such as rumbling, bloating, and altered bowel habits, including both constipation and diarrhea), and overall reduced quality of life. Also, negative changes in the microbiota may be associated with a more frequent development of postoperative complications and complications during chemotherapy.

CASE SUMMARY

Two patients with CRC underwent surgery (laparoscopic left hemicolectomy) and were prescribed chemotherapy regimen consisted of cisplatin, leucovorin, and fluorouracil. Along with prescribed chemotherapy patients took autoprobiotic enterococci. A fecal sample was collected for autoprobiotic preparation, ensuring that the patient had not taken antibiotics, probiotic supplements, or probiotic-containing foods for at least 10 days. An autoprobiotic contained an indigenous strain of Enterococcus faecium (E. faecium) was formulated. The patients received the autoprobiotic strain E. faecium (liquid form with a concentration of 8 Lg CFU/mL) orally at a dose of 50 mL twice daily during 10 days, regardless of meal times, from the first day of cytostatic treatment, throughout the first course of chemotherapy. As a result, autoprobiotic intake improved patient well-being and prevent side effects associated with the use of cytostatics.

CONCLUSION

The use of autoprobiotics in the treatment of CRC is a promising area to reduce the risks of postoperative complications, increase the tolerability of the basic chemotherapeutic regimen, as well as improve the quality of life.

Key Words: Microbiota; Autoprobiotics; Enterococcus spp.; Gut dysbiosis; Colorectal cancer; Case report

Core Tip: The use of individualized autoprobiotic strains of indigenous enterococci can be recommended for postoperative colorectal cancer (CRC) patients undergoing chemotherapy to reduce the risk of postoperative complications, enhance treatment efficacy and tolerability, and improve overall quality of life. Moreover, restoring gut microbiota homeostasis may help lower the risk of CRC recurrence by reducing pro-carcinogenic inflammation associated with gut dysbiosis.

INTRODUCTION

According to the literature, significant disorders of gut microbiota are consistently observed in patients with colorectal cancer (CRC)[1-3]. Disorders of gut microbiota composition are manifesting clinically as abdominal pain, dyspeptic symptoms (such as rumbling, bloating, and altered bowel habits, including both constipation and diarrhea), and overall reduced quality of life[4,5]. Also, negative changes in the microbiota may be associated with a more frequent development of postoperative complications and complications during chemotherapy[6].

This study aims to describe clinical cases demonstrating the application of personalized therapy using indigenous enterococcal strains in a CRC patient following surgery and during chemotherapy. The focus is on the restoration of gut microbiota, improvement of digestive function, and overall enhancement of patient quality of life.

CASE PRESENTATION

Chief complaints

Case 1: The 47-year-old male patient diagnosed with CRC was admitted to the hospital on July 25, 2023, 4 weeks after CRC surgery. Patient was prescribed chemotherapy consisted of cisplatin, leucovorin, and fluorouracil. Chief complains are abdominal pain (2 points on a 10-point scale), diarrhea (2-3 times a day) and sometimes constipation (for two days without stools), dyspepsia (rumbling and bloating).

Case 2: The 54-year-old male patient diagnosed with CRC was admitted to the hospital on November 13, 2023, 4 weeks after CRC surgery. Patient was prescribed chemotherapy consisted of cisplatin, leucovorin, and fluorouracil. Chief complains are abdominal pain (4 points on a 10-point scale), diarrhea (2-3 times a day) and dyspepsia (bloating).

History of present illness

Case 1: These complaints were started in March 2023 and were more severe: Abdominal pain (6 points on a 10-point scale), diarrhea (3-6 times a day) or constipation (for two-three days without stools with sometimes ribbon-like feces after that), dyspepsia (severe rumbling and bloating). Improving in complaints was associated with the operation but the complaints were not completely relief.

Case 2: These complaints were started in July 2023 and were more severe: Abdominal pain (7 points on a 10-point scale), diarrhea (4-5 times a day), dyspepsia (severe bloating). Improving in symptoms was associated with the operation but complains were not completely relief.

History of past illness

Case 1: In March 2023, the patient experienced abdominal pain, diarrhea (3-6 times a day) or constipation (for two-three days without stools with sometimes ribbon-like feces after that), dyspepsia (severe rumbling and bloating). Patient was observed in April-May 2023 via computed tomography (CT), colonoscopy and gastroscopy. CRC 2 cm in diameter was revealed in sigmoid colon; biopsy was taken (low-grade adenocarcinoma) with metastases in regional lymphatic nodes by CT with contrasting. On June 19, 2023 the patient underwent laparoscopic left hemicolectomy and regional lymphatic nodes dissection. Postoperative pathology confirms adenocarcinoma of the sigmoid colon (low-grade) and metastatic tumor cells were detected in 10 of 14 resected lymph nodes (T3N2M0). Adjuvant chemotherapy regimen consisted of cisplatin, leucovorin, and fluorouracil was initiated as eight cycles in 4 weeks after surgery.

Case 2: In July 2023, the patient experienced abdominal pain, diarrhea (4-5 times a day), dyspepsia (severe bloating). Patient was observed in July-August 2023 via CT, colonoscopy and gastroscopy. CRC 2.4 cm in diameter was revealed in sigmoid colon; biopsy was taken (high-grade adenocarcinoma) with metastases in regional lymphatic nodes by CT with contrasting. On October 10, 2023 the patient underwent laparoscopic left hemicolectomy and regional lymphatic nodes dissection. Postoperative pathology confirms adenocarcinoma of the sigmoid colon (high-grade) and metastatic tumor cells were detected in 12 of 15 resected lymph nodes (T3N2M0). Adjuvant chemotherapy regimen consisted of cisplatin, leucovorin, and fluorouracil was initiated as eight cycles in 4 weeks after surgery.

Personal and family history

Case 1: The patient has a healthy lifestyle with no significant occupational or social issues, non-smoker, non-alcohol consumer. No significant genetic disorders or chronic illnesses, also family history of malignant tumors, were reported in the family.

Case 2: The patient has an unhealthy lifestyle (patient is smoker, alcohol consumer-2-3 drinks per week) with no other significant occupational or social issues. No significant genetic disorders or chronic illnesses, also family history of malignant tumors, were reported in the family.

Physical examination

Case 1: On physical examination, the vital signs were as follows: Body temperature, 36.7 °C; blood pressure, 120/74 mmHg; heart rate, 84 beats per min; respiratory rate, 18 breaths per minute. Palpation of the abdomen revealed no soreness. The liver and spleen were not enlarged.

Before and after the autoprobiotic regimen, the following validated questionnaires were completed: The Gastrointestinal Symptom Rating Scale (GSRS) to assess abdominal pain, dyspeptic symptoms and stool; the SF-36 quality of life questionnaire.

The GSRS questionnaire consists of 15 questions, which are converted into 5 scales: Abdominal pain, reflux syndrome, diarrheal syndrome, dyspeptic syndrome, constipation syndrome, and there is also a scoring process on the scale of the total measurement. Complaints concerning the patient in the week preceding the completion of the questionnaire are taken into account. The indicators for each question range from 1 to 7, higher values correspond to more pronounced symptoms of gastroenterological pathology and a lower quality of life[7].

The SF-36 health survey is a widely utilized instrument for assessing overall health status across eight domains: Physical functioning, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each domain is scored on a scale from 0 to 100 points, with higher scores indicating a more favorable health state[8,9].

Case 2: On physical examination, the vital signs were as follows: Body temperature, 36.8 °C; blood pressure, 130/80 mmHg; heart rate, 74 beats per minute; respiratory rate, 20 breaths per minute. Palpation of the abdomen revealed no soreness. The liver and spleen were not enlarged.

Before and after the autoprobiotic regimen, the following validated questionnaires were completed: GSRS to assess abdominal pain, dyspeptic symptoms and stool; the SF-36 quality of life questionnaire.

Laboratory examinations

Case 1: No abnormality was found in routine blood and urine analyses. Before and after the autoprobiotic regimen gut microbiota analysis (real-time polymerase chain reaction) was performed. Initial gut microbiota disorders were characterized by increasing of total bacterial mass, Escherichia coli population, Bacteroides spp. and some of opportunistic bacteria (Proteus vulgaris/mirabilis and Enterobacter spp.); low level of Lactobacillus spp., Bifidobacterium spp.; absence of Faecalibacterium prausnitzii and Enterococcus spp. may be explained not due to the actual absence of these microorganisms, but rather the limitation of the method, which does not detect the number of microorganisms less than 10³ CFU/g.

Case 2: No clinically significant abnormalities were found in routine blood and urine analyses. Before and after the autoprobiotic regimen gut microbiota analysis (real-time polymerase chain reaction) was performed. Initial gut microbiota disorders were characterized by increasing of total bacterial mass, Escherichia coli population, Bacteroides spp. and some of opportunistic bacteria (Enterobacter spp.); low level of Lactobacillus spp., Bifidobacterium spp.; at the same the absence of Enterococcus spp. may be explained not by the absence of these microorganisms in the feces, but by the limitation of the method, when the number of microorganisms less than 10³ is not detected.

Imaging examinations

Case 1: Histological examination confirms adenocarcinoma of the sigmoid colon (low-grade) and metastatic tumor cells were detected in 10 of 14 resected lymph nodes.

Case 2: Histological examination confirms adenocarcinoma of the sigmoid colon (high-grade) and metastatic tumor cells were detected in 12 of 15 resected lymph nodes.

FINAL DIAGNOSIS

Case 1

A diagnosis of CRC was made.

Case 2

A diagnosis of CRC was made.

TREATMENT

Case 1

With a prescribed chemotherapy patient took autoprobiotic treatment. A fecal sample was collected for autoprobiotic preparation, ensuring that the patient had not taken antibiotics, probiotic supplements, or probiotic-containing foods for at least 10 days. Based on this sample, an autoprobiotic preparation containing an indigenous strain of Enterococcus faecium (E. faecium) was formulated. The patient received the autoprobiotic strain E. faecium orally at a dose of 50 mL twice daily, regardless of meal times, throughout the course of chemotherapy. Chemotherapy consisted of cisplatin, leucovorin, and fluorouracil, with the autoprobiotic administered from the first day of cytostatics treatment. The preparation was in a liquid form with a concentration of 8 Lg CFU/mL, and the treatment with autoprobiotic lasted 10 days.

Case 2

With a prescribed chemotherapy patient took autoprobiotic treatment. A fecal sample was collected for autoprobiotic preparation, ensuring that the patient had not taken antibiotics, probiotic supplements, or probiotic-containing foods for at least 10 days. Based on this sample, an autoprobiotic preparation containing an indigenous strain of E. faecium was prepared. The patient received the autoprobiotic strain E. faecium orally at a dose of 50 mL twice daily, regardless of meal times throughout the course of chemotherapy. Chemotherapy consisted of cisplatin, leucovorin, and fluorouracil, with the autoprobiotic administered from the first day of cytostatics treatment. The preparation was in a liquid form with a concentration of 8 Lg CFU/mL, and the duration of autoprobiotic course lasted 10 days.

OUTCOME AND FOLLOW-UP

Case 1

Based on patient-reported outcomes by GSRS questionnaire, the autoprobiotic supplementation alleviated dyspeptic symptoms, prevented severe diarrhea, and maintained stool frequency at no more than three times per day despite ongoing chemotherapy (Table 1).

Table 1 Gastrointestinal Symptom Rating Scale results before and after intake of indigenous non-pathogenic Enterococcus faecium strain in a colorectal cancer 47-year-old patient.

Parameters/results, point	Abdominal pain	Reflux	Diarrhea	Dyspepsia	Constipation
Baseline (AP1)	1	1	4	3	1
Post-treatment (AP2)	0	0	1	1	0

AP1: Scores before autoprobiotic therapy; AP2: Scores after autoprobiotic therapy.

The patient reported good tolerance to chemotherapy. No significant elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, signs of mucositis, or persistent diarrhea exceeding three episodes per day were observed throughout the treatment. On the third day of chemotherapy, the patient experienced diarrhea (3-5 episodes per day), transient visual field narrowing (lasting one hour), abdominal rumbling, and bloating. These symptoms resolved spontaneously and were attributed to chemotherapy-related side effects. Additionally, mild nausea developed on the third day of autoprobiotic intake but resolved without intervention after two days. During the second chemotherapy cycle, which was administered without autoprobiotic support, the patient developed severe diarrhea (15-20 episodes per day), abdominal pain, and mucositis on the second day of treatment, requiring hospitalization for stabilization (Tables 2 and 3).

Table 2 SF-36 quality of life questionnaire results before and after intake of indigenous non-pathogenic Enterococcus faecium strain in a colorectal cancer 47-year-old patient.

Parameters/results, point	Baseline (AP1)	Post-treatment (AP2)
Physical functioning	77	95
Role physical	48	86
Bodily pain	54	70
General health	49	63
Vitality	49	64
Social functioning	59	84
Role emotional	57	80
Mental health	57	68

AP1: Scores before autoprobiotic therapy; AP2: Scores after autoprobiotic therapy.

Table 3 Results of real-time polymerase chain reaction for fecal microbiota composition before and after intake of indigenous non-pathogenic Enterococcus faecium strain in a colorectal cancer 47-year-old patient.

Parameters/results, point	Baseline (AP1)	Post-treatment (AP2)	Normal ranges
Total bacterial mass	3 × 1013	108	≤ 1012
Lactobacillus spp.	< 105	< 105	107-108
Bifidobacterium spp.	2 × 108	< 105	109-1010
Escherichia coli	2 × 109	108	107-108
Bacteroides spp.	3 × 1013	9 × 106	109-1012
Faecalibacterium prausnitzii	Not detected	2 × 106	108-1011
Bacteroides thetaomicron	Not detected	Not detected	≤ 1012
Akkermansia muciniphila	Not detected	Not detected	≤ 1011
Enterococcus spp.1	Not detected	Not detected	≤ 108
Escherichia coli enteropathogenic	Not detected	Not detected	≤ 104
Klebsiella pneumoniae	Not detected	Not detected	≤ 104
Klebsiella oxytoca	Not detected	Not detected	≤ 104
Candida spp.	Not detected	Not detected	≤ 104
Staphylococcus aureus	Not detected	Not detected	≤ 104
Clostridium difficile	Not detected	Not detected	Not detected
Clostridium perfringens	Not detected	Not detected	Not detected
Proteus vulgaris/mirabilis	1010	Not detected	≤ 104
Citrobacter spp.	Not detected	Not detected	≤ 104
Enterobacter spp.	8 × 108	Not detected	≤ 104
Fusobacterium nucleatum	Not detected	Not detected	Not detected
Parvimonas micra	Not detected	Not detected	Not detected
Salmonella spp.	Not detected	Not detected	Not detected
Shigella spp.	Not detected	Not detected	Not detected
Bacteroides fragilis group/Faecalibacterium prausnitzii ratio	> 100	4, 5	0.01-100

¹Absence of Enterococcus spp. may be explained not by the absence of these microorganisms in the feces, but by the limitation of the method, when the number of microorganisms less than 10³ is not detected. AP1: Scores before autoprobiotic therapy; AP2: Scores after autoprobiotic therapy.

This clinical case highlights the high efficacy of indigenous E. faecium in prevention the severity and frequency of chemotherapy-related side effects, emphasizing the critical role of gut microbiota modulation in patients with CRC.

Case 2

The co-administration of the autoprobiotic strain with the first chemotherapy cycle helped maintain digestive system stability during treatment. No statistically significant worsening was observed in gastrointestinal symptoms, as assessed by the GSRS questionnaire. Additionally, quality of life improvements was recorded using the SF-36 questionnaire (Tables 4 and 5).

Table 4 Gastrointestinal Symptom Rating Scale results before and after intake of indigenous non-pathogenic Enterococcus faecium strain in a colorectal cancer 54-year-old patient.

Parameters/results, point	Abdominal pain	Reflux	Diarrhea	Dyspepsia	Constipation
Baseline (AP1)	2	1	3	4	0
Post-treatment (AP2)	0	0	0	1	1

AP1: Scores before autoprobiotic therapy; AP2: Scores after autoprobiotic therapy.

Table 5 SF-36 quality of life questionnaire results before and after intake of indigenous non-pathogenic Enterococcus faecium strain in a colorectal cancer 54-year-old patient.

Parameters/results, point	Baseline (AP1)	Post-treatment (AP2)
Physical functioning	75	92
Role physical	51	84
Bodily pain	53	77
General health	52	68
Vitality	50	67
Social functioning	56	83
Role emotional	57	82
Mental health	55	73

AP1: Scores before autoprobiotic therapy; AP2: Scores after autoprobiotic therapy.

The patient reported good tolerance to chemotherapy. No clinically significant elevation in ALT or AST levels (greater than twice the upper normal limit), severe mucositis, or persistent diarrhea (more than three episodes per day over consecutive days) was observed. Abdominal pain was not reported. Real-time PCR analysis of the fecal microbiota composition revealed significant improvements following autoprobiotic administration (Table 6).

Table 6 Results of real-time polymerase chain reaction for fecal microbiota composition before and after intake of indigenous non-pathogenic Enterococcus faecium strain in a colorectal cancer 54-year-old patient.

Parameters/results, point	Baseline (AP1)	Post-treatment (AP2)	Normal ranges
Total bacterial mass	2 × 1012	7 × 1011	≤ 1012
Lactobacillus spp.	< 105	< 105	107-108
Bifidobacterium spp.	6 × 108	109	109-1010
Escherichia coli	2 × 108	108	107-108
Bacteroides spp.	2 × 1012	7 × 1011	109-1012
Faecalibacterium prausnitzii	109	3 × 109	108-1011
Bacteroides thetaomicron	109	3 × 105	≤ 1012
Akkermansia muciniphila	Not detected	Not detected	≤ 1011
Enterococcus spp.1	Not detected	Not detected	≤ 108
Escherichia coli enteropathogenic	Not detected	Not detected	≤ 104
Klebsiella pneumoniae	Not detected	Not detected	≤ 104
Klebsiella oxytoca	Not detected	Not detected	≤ 104
Candida spp.	Not detected	Not detected	≤ 104
Staphylococcus aureus	Not detected	Not detected	≤ 104
Clostridium difficile	Not detected	Not detected	Not detected
Clostridium perfringens	Not detected	Not detected	Not detected
Proteus vulgaris/mirabilis	Not detected	Not detected	≤ 104
Citrobacter spp.	Not detected	Not detected	≤ 104
Enterobacter spp.	7 × 105	Not detected	≤ 104
Fusobacterium nucleatum	Not detected	Not detected	Not detected
Parvimonas micra	Not detected	Not detected	Not detected
Salmonella spp.	Not detected	Not detected	Not detected
Shigella spp.	Not detected	Not detected	Not detected
Bacteroides fragilis group/Faecalibacterium prausnitzii ratio	2000	233	0.01-100

¹Absence of Enterococcus spp. may be explained not by the absence of these microorganisms in the feces, but by the limitation of the method, when the number of microorganisms less than 10³ is not detected. AP1: Scores before autoprobiotic therapy; AP2: Scores after autoprobiotic therapy.

This clinical case highlights the effectiveness of a personalized approach using an individual strain of indigenous non-pathogenic E. faecium as part of a comprehensive therapy to mitigate chemotherapy-associated complications in CRC patients. The autoprobiotic E. faecium demonstrated high efficacy in preventing adverse effects induced by cytostatic agents, further emphasizing the importance of microbiota correction in CRC management.

DISCUSSION

Oncological diseases, including malignant tumors of the gastrointestinal tract (GI), rank among the leading causes of worldwide mortality. Disorders of gut microbiota composition are present in majority of patients with digestive system malignancies, manifesting clinically as abdominal pain, dyspeptic symptoms (such as rumbling, bloating, and altered bowel habits, including both constipation and diarrhea), and overall reduced quality of life. According to the literature, significant disorders of gut microbiota are consistently observed in patients with CRC. A meta-analysis by Wu et al[1] demonstrated a reduction in microbial diversity and an increased prevalence of specific taxa in CRC patients. Of particular interest is the frequent overgrown of genera such as Fusobacterium, Peptostreptococcus, Bacteroides, Eubacterium, Prevotella, Clostridium, and Campylobacter, as well as members of the Enterobacteriaceae family[1]. A strong correlation has been established between CRC and the elevated of specific bacterial species amount, including Bacteroides fragilis, Fusobacterium nucleatum, Streptococcus spp., Parvimonas micra, Peptostreptococcus stomatis, and Enterobacter spp.[2-4]. Moreover, pathogenic Escherichia coli[5], Enterococcus faecalis[6], mucolytic bacteria such as Akkermansia muciniphila[10], and cholesterol synthesis inducers like Peptostreptococcus anaerobius, which stimulate colonocyte proliferation[11], play critical roles in CRC pathogenesis. Conversely, certain bacterial genera, including Collinsella, Slackia, Faecalibacterium, and Roseburia, exhibit anti-carcinogenic properties, highlighting the complex interplay between the gut microbiota and CRC development[12-15].

Surgical intervention combined with antibacterial therapy often leads to pronounced physiological consequences, as evidenced by significant alterations in clinical and laboratory parameters, as well as disruptions in gut microbiota composition. These microbial shifts create a predisposition for severe complications, including abdominal sepsis, pseudomembranous colitis, antibiotic-associated dysbiosis, nonspecific colitis, and mucositis, among others[16-18]. Postoperative complications can arise both from the mechanical aspects of surgery and from infectious processes. Also, to prevent tumor progression, continued treatment with cytostatic agents (than also have many adverse effects and complications) remains essential. When chemotherapy is administered, its affects gut microbiota and negatively changes an overall patient health. A significant proportion of chemotherapy-related adverse effects stem from its impact not only on tumor cells but also on gut microbiota, exacerbating dysbiosis—a condition already prevalent in oncological pathology[19]. Furthermore, quality of life is negatively affected by the psychological disorders after CRC diagnosis, with an increased risk of anxiety and depressive disorders, both of which are associated with gut dysbiosis. One of the most critical adverse effects of chemotherapy in CRC patients is intestinal mucositis. Notably, gut microbiota plays a direct role in the pathogenesis of mucositis, highlighting its complex involvement in treatment-related complications[20,21].

To prevent chemotherapy-induced dysbiosis and support gut microbiota recovery, patients require targeted therapeutic interventions. The beneficial role of such treatments in restoring microbiota disrupted by cytostatics has been demonstrated in multiple studies, both in laboratory animals and clinical settings[22-25]. Early correction of gut microbiota disturbances is strongly recommended, as it not only reduces colonic inflammation and accelerates the recovery of gastrointestinal motility but also alleviates chemotherapy-associated dyspepsia, ultimately improving the quality of life for CRC patients. Probiotic bacteria, including Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus, Lactobacillus plantarum 299v, L. plantarum, L. casei, Bifidobacterium spp. (particularly B. longum), and Saccharomyces cerevisiae, have demonstrated antitumor protective mechanisms[26-30]. Role of probiotics Akkermansia muciniphila in the progression or inhibition of CRC has not yet been determined. By the results of some studies, a decrease in the number of A. muciniphila was associated with severe CRC symptoms and A. muciniphila improves the effect of antitumor immunity[31]. But another studies suggested that A. muciniphila level in gut was higher or increased in CRC patients compared to healthy individuals, inflammation and tumorigenesis in the gut might promoted by A. muciniphila[32].

The anticancer efficacy of probiotics is attributed to their ability to inhibit pathogenic bacteria colonization of the gut mucosa, enhance barrier functions, stimulate mucin production, and promote tight junction protein expression. Additionally, probiotics modulate immune homeostasis by promoting Treg-cell proliferation, regulating pro-inflammatory cytokine production, and inducing apoptosis in cancer cells[33]. The use of probiotics is recommended as part of the comprehensive management of CRC patients at all stages, including the perioperative and long-term postoperative periods, as well as during and after chemotherapy and radiotherapy[16,34,35].

Despite their widespread use, conventional probiotics are not always effective in the postoperative period or in reducing the adverse effects of chemotherapy. This may be attributed to the low persistence of foreign probiotic strains in the host microbiota, influenced by colonization resistance and their rapid elimination from the gastrointestinal tract within 3-5 days. In some cases, probiotics may even induce adverse effects, such as acidosis, dyspepsia, and infectious complications[36]. Additionally, the criteria for personalized selecting an optimal probiotic strain remain unclear. To correction chemotherapy-induced dysbiosis in CRC patients and ensure a more personalized approach to probiotic therapy, the use of autoprobiotics should be considered[37]. Autoprobiotic bacterial strains are derived from an individual's own microbiota and are specifically designed to restore their microbial ecology. Since immunological tolerance to indigenous microbial strains is established early in life, these bacteria integrate seamlessly with the host microbiota without triggering immune conflicts[38]. This allows autoprobiotics to persist longer in the gut and exert more substantial therapeutic effects than commercially available probiotics. The use of autoprobiotics as a personalized functional food product represents a novel therapeutic strategy with several advantages over conventional probiotics. One of the key benefits of indigenous non-pathogenic Enterococcus strains is their biocompatibility with the host microbiota, adaptation to the gut environment, minimal immunological burden, and positive effects on digestion, as well as immune, endocrine, and nervous system functions. These benefits have been demonstrated in experimental dysbiosis models and in pilot clinical studies involving patients with irritable bowel syndrome, metabolic syndrome, CRC post-surgical therapy, axial spondyloarthritis, and Parkinson’s disease[38-44].

We chose Enterococcus spp. for two important reasons: (1) Enterococci belong to the family of lactic acid bacteria colonizing both the large and small intestines of the human body and can be found in everybody’s microbiota; and (2) These bacteria were more effective in our previous experiments, when comparing the effects of indigenous enterococci, lactobacilli, bifidobacteria, and their mixtures on models of experimental dysbiosis and on the cell culture[38]. In addition, these bacteria can be easily cultivated and do not die as quickly as bifidobacteria or lactobacilli in the presence of oxygen. Genetic studies of enterococci revealed that probiotic strains selected for human consumption are quite different from clinical isolates by the organization of their genomes, the presence (or absence) of virulence genes, and the presence (or absence) of antibiotic resistance genes[45]. Not all enterococcal strains are the same when it comes to considering their potential pathogenicity. Modern techniques and available molecular tools make the selection of a strain without any putative virulent factors quite simple.

The presence of gastroenterological complaints (abdominal pain, stool disorders and bloating) may be due to incomplete restoration of bowel function after surgery. The improvement of the gut microbiota after the use of autoprobiotic enterococci in these cases contributes not only to better tolerability of chemotherapy. But also the relief of complaints.

Based on the information provided, also when compare dyspeptic symptoms before and after chemotherapy, it can be stated that patients taking autoprobiotics during chemotherapy did not experience the severe complications that they experience according to the literature if they do not take autoprobiotics. Also we can see that in case report 1: While taking autoprobiotics, there were no symptoms that the first patient experienced without taking them during chemotherapy. For a more accurate assessment of the effectiveness of autoprobiotics, expanded studies are needed to include more patients and divide them into a study group and a comparison group to assess the differences between the groups. For these clinical cases interleukins level was not assessment. We plane to include cytokine biomarkers [e.g., tumor necrosis factor-α, interleukin (IL)-8, IL-10, IL-1β, IL-6, IL-18] to link changes in the microbiota with clinical advances in the future studies.

CONCLUSION

The use of individualized autoprobiotic strains of indigenous non-pathogenic enterococci can be recommended for postoperative CRC patients undergoing chemotherapy to reduce the risk of postoperative complications, enhance treatment efficacy and tolerability, and improve overall quality of life. Moreover, restoring gut microbiota content may help lower the risk of CRC recurrence by reducing pro-carcinogenic inflammation associated with gut dysbiosis.