Researchers at China's Jiangxi Cancer Hospital and Nanchang University conducted a double-blind RCT to assess the impact of a probiotic combination on oral mucositis, a common and unpreventable complication nasopharyngeal carcinoma patients experience when undergoing concurrent radiochemotherapy (CCRT).
Probiotics versus placebo
They recruited 99 patients with locally advanced nasopharyngeal carcinoma who were undergoing CCRT and randomly assigned them to receive either a probiotic combination or placebo during radiochemotherapy, with the incidence of severe oral mucositis (grade 3 or higher) the primary outcome of the study.
The probiotic combination, Bifico, was provided by Shanghai Sine Pharmaceutical Co., and contained Bifidobacterium longum, Lactobacillus lactis and Enterococcus faecium.
Subsequently, the researchers reported that the patients who had been administered the probiotic combination experienced a significant reduction in the severity of oral mucositis: the incidences of the different grades of oral mucositis in the supplemented group and placebo group were recorded as 12.07% and 0% (grade 0), 55.17% and 0% (grade 1), 17.24% and 54.29% (grade 2), and 15.52% and 45.71%, respectively.
At the same time, while CCRT reduced the patients immune cell count drastically, probiotic supplementation was shown to have "markedly lowered" the reduction rates of these cells: CD3+ T cell reduction fell from 69.72% to 45.49%, CD4+ T cell reduction from 76.59% to 52.85%, and CD8+ T cell reduction from 62.94% to 29.76% after CCRT.
Furthermore, high throughput sequencing results indicated that CCRT had led to a disturbance in the patients' intestinal diversity after CCRT, but only those in the supplemented group experienced a restoration in microbial diversity to healthy levels.
The researchers wrote: "B. longum, L. lactis, and E. faecium have the potential to be the backbone of cancer therapy and to be used in cancer care in the future.
"Evidence has indicated that exposure to probiotics boosts the initiation of memory T and B cells, adaptive immunity and the immune system, and corrects the microbial-based education of immune cells, which may affect the production of immunoglobulin A."
They added that the patients who had taken the probiotic combination saw 'significantly enhanced' T-cell numbers, compared to those in the placebo group. This meant greater immunity by way of CD3+ T cells, which are crucial to cell-mediated immunity.
Additionally, CD8+ T cells help to modulate immune responses to pathogens and tumour cells by directing overall immune responses and by killing cancer cells, as well as infected and otherwise damaged cells.
Following the gut
The researchers had also monitored dynamic intestinal microbiota changes, and found that Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria "constituted the dominant phyla and accounted for a majority of the total sequencing numbers" in both the probiotic and placebo groups.
According to earlier research, Firmicutes comprise the largest portion of human gut microbiota, and is linked to energy resorption and possibly, the onset of diabetes and obesity.
In addition, Bacteroidetes' presence in the human intestinal tract is closely connected to nutritional modulation and adverse effects of chemotherapy.
The researchers further reported that the probiotic combination used in the study "greatly enhanced the efficacy and reduced the toxicity of chemotherapeutic agents and radiotherapy by sustaining the bacterial homeostasis of the intestines".
Conclusions on the combination
The study's results led them to write that supplementation with a probiotic combination of Bifidobacterium longum, Lactobacillus lactis and Enterococcus faecium could effectively reduce radiochemotherapy-induced intestinal microbial disturbances, and improve patients’ capacity for food digestion, absorption, energy production, and immunity, either directly or indirectly.
This could in turn lead to a lowered incidence and severity of oral mucositis in nasopharyngeal carcinoma patients.
In conclusion, the researchers wrote: "For the first time, this study indicated that the probiotic combination had significantly enhanced the immunity of patients, reduced oral mucositis, and was beneficial for restoring microbial diversity after the end of CCRT.
"Therefore, this randomised clinical trial shows the benefits of oral probiotics for preventing oral mucositis in patients with cancer during radiochemotherapy.
"Future studies should be performed for the optimisation of the dose and regimen with a larger group of patients, and animal experiments should be performed to explore the potential mechanisms that underlie its sound effect."
"A Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics to Reduce the Severity of Oral Mucositis Induced by Chemoradiotherapy for Patients With Nasopharyngeal Carcinoma"
Authors: Chunling Jiang, et al.