Effects of probiotics on chemotherapy in patients with lung cancer

Abstract

Chemotherapy damages the intestinal mucosa, causing adverse gastrointestinal reactions. Clostridium butyricum (C. butyricum) reduces the incidence of diarrhea in digestive diseases, including inflammatory bowel disease. Therefore, the aim of the present study was to investigate the role of C. butyricum in patients undergoing chemotherapy. A total of 41 participants with lung cancer were enrolled, and divided into the C. butyricum (CB) or placebo group using 1:1 randomization to obtain 20 CB and 21 placebo participants. On the first and last day of the 3-week intervention, blood and stool samples were collected and analyzed. To analyze stool flora, 16S ribosomal RNA sequencing was performed. The incidence of chemotherapy-induced diarrhea was lower in the CB group compared with the placebo group. The lymphocyte count and platelet/lymphocyte ratio (PLR) was markedly altered between the two groups. Neutrophil/lymphocyte ratio (NLR) and PLR decreased within the CB group. At week 3, the lymphocyte/monocyte ratio (LMR) was higher in the CB group compared with the placebo group. Alterations in lymphocyte subsets and immunoglobulin levels were not significantly different. Albumin (ALB) level and weight did not differ significantly between the two groups. At 3 weeks the total flora diversity did not decrease in either group. Phyla in the CB group varied slightly, while the proportion of Firmicutes in the placebo group decreased significantly. No statistically significant difference was observed between the two groups, though the genera producing short-chain fatty acids tended to increase, and the pathogenic genera tended to decrease in the CB group, which was almost the opposite of the observation in the placebo group. Operational taxonomy unit analysis revealed a notable increase in beneficial flora, including the Clostridium and Lactobacillus genera of the CB group, compared with the placebo group. The present study highlighted that C. butyricum reduced chemotherapy-induced diarrhea in patients with lung cancer, reduced the systemic inflammatory response system and encouraged homeostatic maintenance.

Keywords: chemotherapy; intestinal microflora; probiotic; systemic inflammatory response.

Figure 1.

Flow chart of study. Patients with lung cancer were randomly divided at a 1:1 ratio to receive CB or the placebo treatment. Blood and stool specimens were collected at baseline. From the baseline onward, CB or the placebo was administered at a dose of three tablets/day, three times per day, for a total of 3 weeks. After 3 weeks, blood and stool samples were collected again. CB, Clostridium butyricum.

Figure 2.

Peripheral blood routine and systemic inflammatory response indicators. (A) Significant differences were identified in LYM between the two groups. NLR decreased significantly in the CB group. At week 3, LMR was significantly higher in the CB group compared the placebo group. (B) PLR decreased significantly in the CB group. (C) The changes of LYM between two groups demonstated significant difference. (D) The changes of PLR between two groups demonstrated significant difference. NEU, neutrophil; LYM, lymphocyte; MON, monocyte; PLT, platelet; NLR, neutrophil lymphocyte ratio; PLR, platelet/lymphocyte ratio; LMR, lymphocyte/monocyte ratio; CB, Clostridium butyricum. *P<0.05.

Figure 3.

Rarefaction curve. Curves tended to plateau as the number of sequencing events increased, suggesting that the samples were completely sequenced. OTU, operational taxonomy unit.

Figure 4.

Diversity indexes. (A) Shannon and (B) Chao indexes. The differences between groups and time points were compared, and no significant differences were indicated. The change between groups was also not significantly different. CB, Clostridium butyricum.

Figure 5.

PCoA analysis. PCoA analysis on OTU levels at (A) baseline and (B) week 3. PC1 and PC2 indicates the two most important factors impacting the grouping. No significant impact was identified to the grouping at the two time points. T1: CB group at baseline; T2: CB group at week 3. C1: placebo group at baseline; C2: placebo group at week 3. CB, Clostridium butyricum; PCoA, principal coordinates analysis; OTU, operational taxonomy unit. PC, principal coordinates; C, control; T, treatment.

Figure 6.

Differences in phylum level in the (A) CB and (B) placebo groups at two time points. Four primary phyla were identified. The proportion of phyla altered in the CB group, while the proportion of Firmicutes decreased significantly in the placebo group. CB, Clostridium butyricum; C, control; T, treatment.

Figure 7.

Genus differences in the CB and placebo groups. No significant difference was observed in either group. However, the most beneficial genera including Faecalibacterium, Lactobacillus, Clostridum, Blautia and Roseburia were elevated in number. The pathogenic bacteria Escherichia/Shigella decreased in the CB group, and increased in the placebo group. CB, Clostridium butyricum.