Randomised, double-blind, placebo-controlled trial of oral probiotic Streptococcus salivarius M18 on head and neck cancer patients post-radiotherapy: a pilot study

Abstract

Xerostomia detrimentally affects the oral health of many head and neck cancer patients who undergo radiotherapy. Its sequelae become an ongoing burden for patients that often manifest as periodontal disease and dental decay. Bacteria play a major role in the pathogenesis of these conditions and here we explore the use of an oral probiotic to beneficially modulate the oral bacterial community postradiotherapy. In this pilot study, a four-week intervention with oral probiotic lozenges containing Streptococcus salivarius M18 was trialled in seven patients. Post-intervention changes in oral health and in the composition of the plaque and saliva bacterial communities were compared with six patients in a placebo group. An improvement in periodontal screening and plaque index scores was observed in both groups after the intervention period. The oral probiotic lozenges did not significantly impact bacterial community composition or diversity, nor did the probiotic lozenges increase the relative sequence abundance of ZOTU_1 (the probiotic-associated sequence assigned to S. salivarius) detected in the samples. Network analyses suggest negative interactions occurred between ZOTU_1 and species from the periopathogenic genera Campylobacter, Fretibacterium, Selenomonas and Treponema but further investigation is required to more fully understand the beneficial properties of this oral probiotic. Head and neck cancer describes a group of malignant tumours that often require radiotherapy as part of the treatment approach. Due to the close proximity of the salivary glands to the radiation portal, many head and neck cancer patients sustain permanent radiation-induced damage to the salivary glands during radiotherapy 1,2. Subsequently, salivary gland function is reduced, resulting in chronic hyposalivation and xerostomia (dry mouth) that causes considerable discomfort, compromises mastication and speech, increases the risk of oral health complications and decreases the quality of life for many patients 1,3,4. Hyposalivation and loss of salivary buffering capacity lead to a decrease in the pH of saliva and a shift to acidogenic and cariogenic bacteria, including an increase the in abundance of Streptococcus mutans and Lactobacillus spp. 5-7. These effects, combined with a decrease in the mechanical flushing mechanism of saliva to reduce plaque build-up, leave patients prone to post-radiotherapy gingivitis, periodontal disease and rampant dental decay 2,3,8. Oral probiotics, primarily those containing lactobacilli, have been successfully shown to decrease the abundance of periopathogens in sub-and supra-gingival plaque, significantly improve plaque index and periodontal

Probiotic Supplements on Oncology Patients’ Treatment-Related Side Effects: A Systematic Review of Randomized Controlled Trials

“…Two of these studies used a single probiotic strain, S. salivarius M18 and L. casei LC9018 respectively, and the remaining study used a combination of L. acidophilus , L. rhamnosus , B. longum, and Saccharomycesboulardii . In line with the findings of Shao and collaborators (2014) [ 38 ], not only did Doppalapudi and collaborators (2020) [ 42 ] and Vesty and collaborators (2020) [ 41 ] observe clinical improvements driven by probiotic-induced changes in the oral microbiota but also a potential mechanism to improve these performance status-related side effects throughout other modulating host immune response and microbial interactions. Having said that, only one study [ 43 ] assessed the effect of probiotics in malignant pleural effusion, which is one of the most common complications in lung cancer.…”

“…Concerning to the impact of probiotics in patients’ general well-being and activities of daily life, three trials (15%) evaluated their effects over a 4-week treatment period [ 41 , 42 , 43 ]. Two of these studies used a single probiotic strain, S. salivarius M18 and L. casei LC9018 respectively, and the remaining study used a combination of L. acidophilus , L. rhamnosus , B. longum, and Saccharomycesboulardii .…”

“…On the other hand, oral mucositis and oral health stand as one of the most treated side effects as they significantly reduce the patients’ quality of life [ 60 ]. In that matter, probiotics such as B. longum (BCMC02120, BB-536), L. lactis BCMC12451, E. faecium , and L. brevis CD2 have shown to reduce the incidence of severe oral mucositis by promoting the growth and protection of the bacterial flora and, as a result, decreasing the number of adverse effects, severity, and incidence of mucositis [ 20 , 40 , 41 , 42 ]. These findings are in agreement with those of Vesty and collaborators (2020) [ 41 ], who identified that using S. salivarius M18 improved patients’ quality of life by reducing the number of oral infections (candidiasis) and adverse effects (mucositis, diarrhea) that these patients experienced after their treatments.…”

Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions

“…While these lesions usually resolve within a few weeks, they are reportedly painful and can be so severe as to disrupt HNC treatment regimens [ 11 ]. In addition to decreased volume, changes in saliva quality (e.g., pH, protein composition, consistency) affect the buffering capacity and digestive functions of saliva, as well as the composition of oral microbiota [ 27 , 28 , 29 , 30 ].…”

“…Unfortunately, current management strategies are inadequate, relying on transient symptom relief afforded by artificial saliva products [ 41 , 42 ] or sialagogues that promote saliva production from residual acinar cells, as discussed in the therapeutics section of the present review [ 15 ]. However, there are some promising strategies for RT-induced salivary gland dysfunction, such as recently evaluated oral probiotic lozenges [ 30 ]. We will discuss novel therapies being investigated for radioprotection or salivary gland regeneration at the end of this review.…”