Key Points
Background: Why This Research Matters
Study Design and Methods
Who Participated in the Study
The Probiotic Treatment Protocol
Key Findings: Faster Bowel Recovery and Less Diarrhea
Other Postoperative Outcomes
Infectious and Non-Infectious Complications
Clinical Implications: What This Means for Patients
Study Limitations
Recommendations for Patients
Frequently Asked Questions
Source Information

Key Points

In a randomized trial of 60 colorectal cancer surgery patients, probiotics before and after surgery shortened time to first flatus and first bowel movement.
Postoperative diarrhea occurred in 27% of probiotic patients versus 53% of placebo patients, a statistically significant difference.
The probiotic combination contained Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, taken as 2 grams three times daily for 12 days.
Bacteremia was 10% with probiotics versus 30% with placebo, but this difference was not statistically significant.
Patients should talk to their surgeon before using probiotics; strains, dose, and timing matter, and results are not guaranteed.

Background: Why This Research Matters

The human gut is home to trillions of microorganisms — nearly 10 times as many as the number of cells in the human body. These gut microbes fluctuate significantly in response to various diseases, including obesity, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colorectal cancer (CRC).

When the natural balance of gut bacteria is disrupted — a condition called dysbiosis — it can have serious consequences. In cancers of the colon and rectum, dysbiosis is especially common because these tissues are directly exposed to microbes. Research has confirmed a strong link between gut microbiota imbalance and cancer progression. Several opportunistic bacteria, including Helicobacter hepaticus, Streptococcus bovis, enterotoxigenic Escherichia coli (ETEC), enterotoxigenic Bacteroides fragilis (ETBF), and Fusobacterium nucleatum, have been shown to contribute to colorectal cancer development and affect clinical prognosis.

Postoperative infection is a particularly poor indicator for surgical cancer treatment. Intestinal dysbiosis-induced bacterial translocation — where bacteria move from the gut into the bloodstream or other tissues — is considered a major driver of postoperative infection. In addition, the inappropriate use of antibiotics, chemotherapy, or even mechanical bowel preparation before surgery can worsen microecological imbalance and increase the risk of various infections.

This is where probiotics come in. Probiotics are beneficial bacteria that help sustain a healthy gut microenvironment. Their anti-infection and anti-cancer effects are thought to work through three main mechanisms:

Mutagen binding, competitive inhibition, and degradation — probiotics can bind to harmful substances and outcompete pathogenic bacteria
Enhancement of the host's innate and adaptive immunity — they help strengthen the body's natural defense systems
Stimulation of beneficial gut microbes and improvement of metabolic activity — they support a healthier microbial community

While oral probiotic administration has been suggested as beneficial for patients undergoing colorectal surgery, the specific postoperative clinical benefits remained largely unexplored before this study. The researchers designed this randomized controlled trial to evaluate whether perioperative probiotic treatment (given before and after surgery) could reduce infections and improve recovery in patients undergoing confined colorectal cancer resection.

Study Design and Methods

This was a randomized, double-blind, placebo-controlled clinical trial — considered the gold standard in medical research. "Double-blind" means that neither the patients nor the researchers knew who was receiving the actual probiotic treatment and who was receiving the placebo, eliminating bias.

The study was conducted from November 2011 to September 2012 at the Shanghai Jiao Tong University Affiliated Sixth People's Hospital in Shanghai, China. The research protocol was approved by the hospital's ethics committee, and all participants signed written informed consent. The trial was registered publicly before enrollment began (Registration number: ChiCTR-TRC-13003332).

Patients were randomly assigned in a 1:1 proportion (meaning equal chances of being in either group) according to a list of randomization numbers. A power of 80% and an alpha error of 5% were set to calculate the appropriate sample size. Statistical analysis was conducted using IBM SPSS Statistics 20.0 and GraphPad Prism 6 software.

To measure outcomes, researchers used unpaired Student's t-tests for continuous variables, Pearson's Chi-square test and Fisher's exact test for categorical variables, and Mann-Whitney U test for ordinal variables. All tests were double-tailed, and p values below 0.05 were considered statistically significant. In plain language, a p value of less than 0.05 means there is less than a 5% probability that the results occurred by chance.

Who Participated in the Study

From November 2011 to September 2012, a total of 92 patients diagnosed with sporadic colorectal cancer were initially recruited. After applying strict eligibility criteria, 13 patients were excluded — either because they refused to participate (5 patients) or because they did not meet the inclusion and exclusion criteria (8 patients).

Of the 79 remaining participants, 37 were randomly assigned to the placebo (control) group and 42 to the probiotics group. However, 7 patients in the placebo group and 12 patients in the probiotics group could not complete the study due to unexecuted or discontinued intervention. The final analysis included 60 eligible patients, with exactly 30 patients in each group.

The study had specific inclusion and exclusion criteria to ensure patient safety and reliable results:

Inclusion criteria:

Age between 25 and 80 years
Receiving confined colorectal cancer resection operation
Able to tolerate curative surgery
Diagnosed with sporadic colorectal cancer by biopsy examination and family history data collection
No evidence of cancer metastasis
Voluntary participation with written informed consent

Exclusion criteria:

Age younger than 25 or older than 80 years
Co-occurrence of other gastroenterological diseases (such as inflammatory bowel disease)
Co-existence of other malignant neoplasms (other types of cancer)
Severe cardiovascular or cerebrovascular diseases that could not tolerate radical surgery
Distant metastasis
Recent use of probiotics, prebiotics, or synbiotics
Recent infection or recent antibiotic use
Emergency surgery or laparoscopic surgery
Neoadjuvant chemotherapy, radiotherapy, or biotherapy before surgery
Evidence of immunodeficiency
Pregnancy

The two groups were very similar at the start of the study. There were no statistically significant differences between the placebo and probiotics groups in terms of gender (p = 0.604), age (p = 0.567), body mass index or BMI (p = 0.895), tumor location (p = 0.855), TNM cancer stage (p = 0.771), or tumor differentiation (p = 0.707).

Specifically, the placebo group had 18 females and 12 males with a mean age of 62.17 ± 11.06 years and an average BMI of 22.07 ± 1.70 kg/m². The probiotics group had 15 females and 15 males with a mean age of 63.90 ± 12.25 years and an average BMI of 22.13 ± 1.77 kg/m².

Preoperative blood tests also showed no significant differences between the two groups for white blood cell count (p = 0.437), hemoglobin (p = 0.371), albumin (p = 0.216), creatinine (p = 0.345), glucose (p = 0.858), triglyceride (p = 0.353), or total cholesterol (p = 0.530). This homogeneity confirmed that the baseline characteristics of the two groups were well matched.

The Probiotic Treatment Protocol

Patients in the probiotics group received a combined probiotic product called Bifico (manufactured by Sine Pharmaceuticals, Shanghai, China), which contained three recognized medicinal bacterial strains:

Bifidobacterium longum (at least 1.0 × 10⁷ colony-forming units per gram)
Lactobacillus acidophilus (at least 1.0 × 10⁷ cfu/g)
Enterococcus faecalis (at least 1.0 × 10⁷ cfu/g)

The dose was 2 grams taken orally three times daily (2g, po, tid) for 12 consecutive days — specifically 5 days before surgery and 7 days after colorectal cancer resection. When oral administration was not feasible on the first day after surgery, the probiotics were given through a gastric tube (gastric gavage). Patients in the placebo group received an identical-looking powder containing maltodextrin and sucrose, with no live probiotics.

Both the probiotic and placebo products were packaged identically and stored at a controlled temperature of 2°C to 8°C. All researchers and patients remained blinded to the treatment assignments throughout the entire intervention period.

All patients received the same standard care:

Conventional rehydration therapy without additional nutritional supplements
A low-residue diet one day before surgery
3 liters of polyethylene glycol electrolyte solution the night before surgery for bowel preparation
One dose of Cefoxitin (an antibiotic) 30 minutes before surgery
Ongoing antibiotics after surgery if intraperitoneal drainage had not been removed or if the patient developed a fever above 38.5°C
All patients underwent open colorectal surgery performed by the same surgeon

Key Findings: Faster Bowel Recovery and Less Diarrhea

The study produced two statistically significant findings that point to meaningful clinical benefits of perioperative probiotics.

1. Faster return of bowel function:

Days to first flatus (passing gas): 3.63 days in the placebo group versus 3.27 days in the probiotics group (p = 0.0274) — a statistically significant improvement
Days to first defecation (bowel movement): 4.53 days in the placebo group versus 3.87 days in the probiotics group (p = 0.0268) — also statistically significant

This means patients taking probiotics regained normal bowel function roughly 9 to 15 hours earlier on average than those taking placebo. For context, a p value of 0.0274 means there is only about a 2.7% probability that this difference occurred by random chance.

2. Significantly lower incidence of diarrhea:

Diarrhea occurred in 26.67% (8 out of 30) of patients in the probiotics group compared to 53.33% (16 out of 30) in the placebo group (p = 0.0352)

In other words, patients taking probiotics were approximately half as likely to experience postoperative diarrhea. Since diarrhea increases the risk of malnutrition, infectious complications, and prolonged hospitalization in colorectal cancer surgery patients, this finding carries important clinical weight.

The relatively high overall rate of diarrhea in both groups may be attributed to the open surgical procedure used in this study and the high proportion of left-sided colorectal carcinomas among participants.

Infectious and Non-Infectious Complications

The study tracked both infectious and non-infectious complications using strict clinical definitions. Here is what they found.

Infectious complications:

Bacteremia (bacteria in the bloodstream): The incidence was 10% (3 out of 30) in the probiotics group compared to 30% (9 out of 30) in the placebo group. Although this difference was notable, it did not quite reach statistical significance (p = 0.0528). This means there is a 5.28% probability the difference was due to chance — just slightly above the 5% threshold for statistical significance.
Wound infection: 3.33% (1 out of 30) in each group, p = 1.000 — no difference
Pneumonia: 16.67% (5 out of 30) in the placebo group vs. 10.00% (3 out of 30) in the probiotics group, p = 0.704 — not statistically significant
Urinary tract infection: 6.67% (2 out of 30) in each group, p = 0.605 — no difference

Non-infectious complications:

Anastomotic leakage (leakage at the surgical connection site): 1 incident in the placebo group vs. 1 incident in the probiotics group, p = 1.000 — no difference
Diarrhea: 53.33% (16 out of 30) in the placebo group vs. 26.67% (8 out of 30) in the probiotics group, p = 0.0352 — the only non-infectious complication with a statistically significant difference
Abdominal distension: 43.33% (13 out of 30) in the placebo group vs. 30.00% (9 out of 30) in the probiotics group, p = 0.284 — not statistically significant

Importantly, no drug side effects and no deaths (mortality) occurred in either group during the study.

Clinical Implications: What This Means for Patients

The researchers concluded that perioperative probiotic administration may help patients undergoing confined colorectal cancer resection achieve faster recovery of bowel function and a lower incidence of diarrhea. The slight reduction in bacteremia (from 30% in the placebo group to 10% in the probiotics group) also suggests that probiotics could be clinically valuable in reducing short-term infectious complications such as bacteremia or even gut-origin sepsis, although this finding did not reach statistical significance in this study.

These findings align with several previous studies that have assessed the benefits of maintaining intestinal microbiota balance with perioperative probiotic treatment in patients undergoing biliary cancer surgery, pancreaticoduodenectomy, liver transplantation, and coloproctectomy. One of the authors' earlier studies also confirmed the anti-inflammatory effects, immune regulation, and gut barrier protection of this combined probiotics formula in an interleukin-10 deficient mice model and Caco-2 cell line.

The improvement in bowel function recovery likely stems from the effects of the combined probiotics on host physiology, including metabolism, intestinal function, bone homeostasis, and even emotion and behavior. Postoperative gastrointestinal symptoms like diarrhea increase the risk of malnutrition, infectious complications, and longer hospital stays in colorectal cancer surgery patients, so reducing diarrhea is a meaningful clinical win.

It is important to note, however, that a previous review study by Peitsidou and colleagues did not advocate combining beneficial microecologics with mechanical bowel preparation in colorectal cancer surgery patients. More research with larger patient cohorts and longer probiotic use is needed to confirm these results.

Study Limitations

Every clinical study has limitations, and the authors were transparent about two key ones:

Short duration of probiotic use: The probiotic treatment was given for only 12 consecutive days (5 days before and 7 days after surgery). A longer course might produce different or more pronounced effects.
No continued probiotic administration after hospital discharge: Patients did not continue taking probiotics once they left the hospital. The authors noted that follow-up studies would be appropriate to assess whether long-term probiotic use benefits patients who subsequently undergo chemotherapy.

Additional considerations include the small sample size (only 30 patients per group) and that the study was conducted at a single hospital in China. All patients received open surgery from a single surgeon, which helps standardize the procedure but may limit generalizability to other surgical approaches, such as laparoscopic surgery.

Recommendations for Patients

Based on this research, here are some practical considerations for patients preparing for colorectal cancer surgery:

Talk to your surgeon about probiotics. Ask whether a specific probiotic formulation might be appropriate in your case. This study used a specific combination of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis taken as 2 grams three times daily, starting 5 days before surgery and continuing 7 days after.
Not all probiotics are created equal. The bacteria strains, dosage, and timing matter. This study used a medicinal combination product with at least 1.0 × 10⁷ colony-forming units per gram of each strain. Over-the-counter probiotic supplements may not replicate these results.
Never start probiotics without your doctor's approval. Some patients were excluded from this trial, including those with immunodeficiency, recent infections, recent antibiotic use, or those who had recently taken other probiotic products. Safety comes first.
Expect faster bowel recovery. If you take probiotics before and after colorectal surgery, your bowel function may return slightly earlier — about half a day sooner for gas and bowel movements based on these findings.
Be aware of the diarrhea benefit. The most striking result was the halving of postoperative diarrhea rates (from 53% down to 27%). This could mean less discomfort and a lower risk of malnutrition and complications.
Remember that results are not guaranteed. This was a small study, and several measures (such as hospital stay length and overall complication rates) did not show statistically significant improvements. Discuss with your healthcare team whether probiotics are right for your specific situation.

Always remember that this is one clinical trial among a growing body of research. Patients should discuss any supplement use, including probiotics, with their surgical and oncology care teams before the procedure. The same principle applies to all aspects of colorectal cancer treatment — decisions should be individualized, informed, and made in partnership with qualified medical professionals.

Frequently Asked Questions

What did this clinical trial test?

This randomized, double-blind, placebo-controlled trial in China tested whether a specific probiotic combination taken 5 days before and 7 days after colorectal cancer surgery could improve recovery. Sixty patients completed the study, with 30 receiving probiotics and 30 receiving placebo. Key outcomes were bowel function recovery and complication rates.

Who was eligible to participate in the trial?

Patients were between 25 and 80 years old and scheduled for confined colorectal cancer resection due to sporadic colorectal cancer, without metastasis. They had to tolerate curative surgery and provide written informed consent. Exclusion criteria included other gastrointestinal diseases, other cancers, severe heart or brain disease, recent antibiotic use, pregnancy, and immune deficiency.

What probiotic product and dose were used?

The probiotics group received a product called Bifico containing three strains: Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis, each at least 1.0 × 10⁷ colony-forming units per gram. The dose was 2 grams taken three times daily for 12 days — starting 5 days before surgery and continuing 7 days after.

Did probiotics reduce infections or other complications?

There was a noticeable but not statistically significant reduction in bacteremia: 10% in the probiotics group versus 30% in the placebo group. No differences were seen for wound infections, pneumonia, urinary tract infections, or anastomotic leakage. No deaths or drug side effects occurred in either group.

Are there study limitations I should know about?

Yes. The trial enrolled only 60 patients at one hospital, and all had open surgery from a single surgeon. Probiotics were given for only 12 days, with no continued use after discharge. More research with larger groups and longer treatment is needed to confirm these findings and see if benefits extend to other surgical approaches.

Source Information

Original Article Title: perioperative probiotics treatment for colorectal cancer-

Authors: Yongzhi Yang, Yang Xia, Hongqi Chen, Leiming Hong, Junlan Feng, Jun Yang, Zhe Yang, Chenzhang Shi, Wen Wu, Renyuan Gao, Qing Wei, Huanlong Qin, and Yanlei Ma (These authors contributed equally: Yongzhi Yang, Yang Xia)

Corresponding Authors: Huanlong Qin, Yanlei Ma, and Qing Wei

Publication: Oncotarget, Vol. 7, No. 7, pages 8432-8438

Dates: Received August 03, 2015; Accepted January 13, 2016; Published January 27, 2016

Funding: This work was supported by grants from the National Natural Science Foundation of China (No.81230057; No.81472262; No.81372615), the National High Technology Research and Development Program (863 Program; Grant No. 2014AA020803), the National Science and Technology Major Projects (2013ZX09103003-16), and the Shanghai Health System Outstanding Young Talent Training Plan (No. XYQ2013118).

Trial Registration: ChiCTR-TRC-13003332 (www.chictr.org)

Affiliated Institutions: Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University; Department of Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Department of Pathology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.

This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not constitute medical advice. Patients should consult their healthcare providers regarding any treatment decisions.

Can Probiotics Improve Recovery After Colorectal Cancer Surgery? What a Clinical Trial Found

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