Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial

BMC Gastroenterol. 2015 Mar 20;15:34. doi: 10.1186/s12876-015-0260-z.


Background: Colorectal liver metastases (CLM) occur frequently and postoperative intestinal infection is a common complication. Our previous study showed that probiotics could decrease the rate of infectious complications after colectomy for colorectal cancer. To determine the effects of the perioperative administration of probiotics on serum zonulin levels which is a marker of intestinal permeability and the subsequent impact on postoperative infectious complications in patients with CLM.

Methods: 150 patients with CLM were randomly divided into control group (n = 68) and probiotics group (n = 66). Probiotics and placebo were given orally for 6 days preoperatively and 10 days postoperatively to control group and probiotics group respectively. We used the local resection for metastatic tumor ,while for large tumor, the segmental hepatectomy. Postoperative outcome were recorded. Furthermore, complications in patients with normal intestinal barrier function and the relation with serum zonulin were analyzed to evaluate the impact on the liver barrier dysfunction.

Results: The incidence of infectious complications in the probiotics group was lower than control group. Analysis of CLM patients with normal postoperative intestinal barrier function paralleled with the serum zonulin level. And probiotics could also reduce the concentration of serum zonulin (P = 0.004) and plasma endotoxin (P < 0.001).

Conclusion: Perioperative probiotics treatment could reduce the serum zonulin level, the rate of postoperative septicemia and maintain the liver barrier in patients undergoing CLM surgery. we propose a new model about the regulation of probiotics to liver barrier via clinical regulatory pathway. We recommend the preoperative oral intake of probiotics combined with postoperative continued probiotics treatment in patients who undergo CLM surgery.

Trial registration: ChiCTR-TRC- 12002841 . 2012/12/21.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacterial Infections / prevention & control*
  • Cholera Toxin / blood*
  • Colorectal Neoplasms / pathology*
  • DNA, Bacterial / blood
  • Double-Blind Method
  • Endotoxins / blood
  • Female
  • Haptoglobins
  • Hepatectomy / adverse effects
  • Humans
  • Intestinal Diseases / prevention & control*
  • Intestinal Mucosa / metabolism*
  • Intraabdominal Infections / prevention & control
  • Liver Neoplasms / secondary
  • Liver Neoplasms / surgery*
  • Male
  • Middle Aged
  • Perioperative Care / methods*
  • Permeability / drug effects
  • Probiotics / administration & dosage*
  • Protein Precursors
  • Sepsis / prevention & control
  • Signal Transduction / drug effects
  • Urinary Tract Infections / prevention & control
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • DNA, Bacterial
  • Endotoxins
  • Haptoglobins
  • Protein Precursors
  • zonulin
  • Cholera Toxin
  • p38 Mitogen-Activated Protein Kinases