Probiotics and Oral Complications of Antineoplastic Therapy in Head and Neck Cancer: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Eligibility Criteria
2.2. Sources of Information
2.3. Search Strategy
2.4. Selection of Studies
2.5. Data Collection Process and Elements
2.6. Outcomes
2.7. Risk of Bias in Individual Studies
2.8. Effect Measures
2.9. Summary of Results
2.10. Reporting Bias Assessment
2.11. Certainty Assessment
3. Results
3.1. Selection of Studies
3.2. Characteristics of the Studies
3.3. Risk of Bias in Individual Studies
3.4. Synthesis of Results by Outcomes of Interest
3.4.1. Effects of Probiotics on Oral Mucositis (OM)
3.4.2. Effects of Probiotics on Oral Candidiasis
3.4.3. Effect of Probiotics on Plaque Index and Periodontal Screening
3.4.4. Effect of Probiotics on Microbiota in Patients with Head and Neck Cancer
4. Discussion
4.1. Fungal Colonisation and Oral Candidiasis
4.2. Periodontal Health and Microbiological Balance
4.3. Future Directions
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Protocol and Registration
Abbreviations
RCT | Randomized controlled trial |
RT | Radiotherapy |
OM | Oral mucositis |
CCRT | Concurrent chemoradiotherapy |
CFU | Colony-forming units |
QT | Chemotherapy |
IMRT | Intensity-modulated radiation therapy |
D | Day |
CPITN | Community Periodontal Index of Treatment Needs |
References
- Taberna, M.; Gil Moncayo, F.; Jané-Salas, E.; Antonio, M.; Arribas, L.; Vilajosana, E.; Peralvez Torres, E.; Mesía, R. The Multidisciplinary Team (MDT) Approach and Quality of Care. Front. Oncol. 2020, 10, 85. [Google Scholar] [CrossRef] [PubMed]
- Buglione, M.; Cavagnini, R.; Di Rosario, F.; Sottocornola, L.; Maddalo, M.; Vassalli, L.; Grisanti, S.; Salgarello, S.; Orlandi, E.; Paganelli, C.; et al. Oral Toxicity Management in Head and Neck Cancer Patients Treated with Chemotherapy and Radiation: Dental Pathologies and Osteoradionecrosis (Part 1) Literature Review and Consensus Statement. Crit. Rev. Oncol. Hematol. 2016, 97, 131–142. [Google Scholar] [CrossRef]
- De Sanctis, V.; Merlotti, A.; De Felice, F.; Trignani, M.; Dell’Oca, I.; Lastrucci, L.; Molteni, M.; Frakulli, R.; Bunkheila, F.; Bacigalupo, A.; et al. Intensity Modulated Radiation Therapy and Oral Mucosa Sparing in Head and Neck Cancer Patients: A Systematic Review on Behalf of Italian Association of Radiation Oncology—Head and Neck Working Group. Crit. Rev. Oncol. Hematol. 2019, 139, 24–30. [Google Scholar] [CrossRef] [PubMed]
- Pfister, D.G.; Spencer, S.; Adelstein, D.; Adkins, D.; Anzai, Y.; Brizel, D.M.; Bruce, J.Y.; Busse, P.M.; Caudell, J.J.; Cmelak, A.J.; et al. Head and Neck Cancers, Version 2.2020. JNCCN J. Natl. Compr. Cancer Netw. 2020, 18, 873–898. [Google Scholar] [CrossRef]
- Epstein, J.B.; Barasch, A. Oral and Dental Health in Head and Neck Cancer Patients. In Cancer Treatment and Research; Springer International Publishing: Cham, Switzerland, 2018; Volume 174. [Google Scholar]
- Jensen, S.B.; Pedersen, A.M.L.; Vissink, A.; Andersen, E.; Brown, C.G.; Davies, A.N.; Dutilh, J.; Fulton, J.S.; Jankovic, L.; Lopes, N.N.F.; et al. A Systematic Review of Salivary Gland Hypofunction and Xerostomia Induced by Cancer Therapies: Prevalence, Severity and Impact on Quality of Life. Support. Care Cancer 2010, 18, 1039–1060. [Google Scholar] [CrossRef]
- Beetz, I.; Schilstra, C.; Visink, A.; Van Der Schaaf, A.; Bijl, H.P.; Van Der Laan, B.F.A.M.; Steenbakkers, R.J.H.M.; Langendijk, J.A. Role of Minor Salivary Glands in Developing Patient-Rated Xerostomia and Sticky Saliva during Day and Night. Radiother. Oncol. 2013, 109, 311–316. [Google Scholar] [CrossRef] [PubMed]
- Schuurhuis, J.M.; Stokman, M.A.; Witjes, M.J.H.; Langendijk, J.A.; Van Winkelhoff, A.J.; Vissink, A.; Spijkervet, F.K.L. Head and Neck Intensity Modulated Radiation Therapy Leads to an Increase of Opportunistic Oral Pathogens. Oral. Oncol. 2016, 58, 32–40. [Google Scholar] [CrossRef]
- Kwiatkowski, D.; Schuch, L.F.; Klaus, N.M.; Martins, M.D.; Hilgert, J.B.; Hashizume, L.N. Oral Microbiota in Head and Neck Cancer Patients during Radiotherapy: A Systematic Review. Support. Care Cancer 2025, 33, 127. [Google Scholar] [CrossRef]
- Kageyama, S.; Nagao, Y.; Ma, J.; Asakawa, M.; Yoshida, R.; Takeshita, T.; Hirosue, A.; Yamashita, Y.; Nakayama, H. Compositional Shift of Oral Microbiota Following Surgical Resection of Tongue Cancer. Front. Cell Infect. Microbiol. 2020, 10, 600884. [Google Scholar] [CrossRef]
- Radaic, A.; Ye, C.; Parks, B.; Gao, L.; Kuraji, R.; Malone, E.; Kamarajan, P.; Zhan, L.; Kapila, Y.L. Modulation of Pathogenic Oral Biofilms towards Health with Nisin Probiotic. J. Oral Microbiol. 2020, 12, 1809302. [Google Scholar] [CrossRef]
- Lin, C.W.; Chen, Y.T.; Ho, H.H.; Hsieh, P.S.; Kuo, Y.W.; Lin, J.H.; Liu, C.R.; Huang, Y.F.; Chen, C.W.; Hsu, C.H.; et al. Lozenges with Probiotic Strains Enhance Oral Immune Response and Health. Oral Dis. 2022, 28, 1723–1732. [Google Scholar] [CrossRef]
- Zhang, Q.; Shan, B.; Xu, X.; Mao, B.; Tang, X.; Zhao, J.; Zhang, H.; Cui, S.; Chen, W. Lactiplantibacillus Plantarum CCFM8724 Reduces the Amounts of Oral Pathogens and Alters the Oral Microbiota in Children With Dental Caries: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Am. Nutr. Assoc. 2022, 42, 361–370. [Google Scholar] [CrossRef] [PubMed]
- Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. Expert Consensus Document: The International Scientific Association for Probiotics and Prebiotics Consensus Statement on the Scope and Appropriate Use of the Term Probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514. [Google Scholar] [CrossRef]
- Sniffen, J.C.; McFarland, L.V.; Evans, C.T.; Goldstein, E.J.C. Choosing an Appropriate Probiotic Product for Your Patient: An Evidence-Based Practical Guide. PLoS ONE 2018, 13, e0209205. [Google Scholar] [CrossRef] [PubMed]
- López-López, A.; Camelo-Castillo, A.; Ferrer, M.D.; Simon-Soro, Á.; Mira, A. Health-Associated Niche Inhabitants as Oral Probiotics: The Case of Streptococcus Dentisani. Front. Microbiol. 2017, 8, 379. [Google Scholar] [CrossRef]
- Seminario-Amez, M.; López-López, J.; Estrugo-Devesa, A.; Ayuso-Montero, R.; Jané-Salas, E. Probiotics and Oral Health: A Systematic Review. Med. Oral Patol. Oral Cir. Bucal 2017, 22, e282–e288. [Google Scholar] [CrossRef] [PubMed]
- Yang, B.; Li, W.; Shi, J. Preventive Effect of Probiotics on Oral Mucositis Induced by Anticancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. BMC Oral Health 2024, 24, 1159. [Google Scholar] [CrossRef]
- Higgins, J.P.T.; Altman, D.G.; Gøtzsche, P.C.; Jüni, P.; Moher, D.; Oxman, A.D.; Savović, J.; Schulz, K.F.; Weeks, L.; Sterne, J.A.C. The Cochrane Collaboration’s Tool for Assessing Risk of Bias in Randomised Trials. BMJ 2011, 343, d5928. [Google Scholar] [CrossRef]
- Lin, B.; Zhao, F.; Liu, Y.; Wu, X.; Feng, J.; Jin, X.; Yan, W.; Guo, X.; Shi, S.; Li, Z.; et al. Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy. Front. Endocrinol. 2022, 13, 834674. [Google Scholar] [CrossRef]
- Mokhtar, M.; Rismayuddin, N.A.R.; Mat Yassim, A.S.; Ahmad, H.; Abdul Wahab, R.; Dashper, S.; Arzmi, M.H. Streptococcus Salivarius K12 Inhibits Candida Albicans Aggregation, Biofilm Formation and Dimorphism. Biofouling 2021, 37, 767–776. [Google Scholar] [CrossRef]
- de Sanctis, V.; Belgioia, L.; Cante, D.; la Porta, M.R.; Caspiani, O.; Guarnaccia, R.; Argenone, A.; Muto, P.; Musio, D.; de Felice, F.; et al. Lactobacillus Brevis CD2 for Prevention of Oral Mucositis in Patients with Head and Neck Tumors: A Multicentric Randomized Study. Anticancer Res. 2019, 39, 1935–1942. [Google Scholar] [CrossRef] [PubMed]
- Jiang, C.; Wang, H.; Xia, C.; Dong, Q.; Chen, E.; Qiu, Y.; Su, Y.; Xie, H.; Zeng, L.; Kuang, J.; et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics to Reduce the Severity of Oral Mucositis Induced by Chemoradiotherapy for Patients with Nasopharyngeal Carcinoma. Cancer 2019, 125, 1081–1090. [Google Scholar] [CrossRef] [PubMed]
- Limaye, S.A.; Haddad, R.I.; Cilli, F.; Sonis, S.T.; Colevas, A.D.; Brennan, M.T.; Hu, K.S.; Murphy, B.A. Phase 1b, Multicenter, Single Blinded, Placebo-Controlled, Sequential Dose Escalation Study to Assess the Safety and Tolerability of Topically Applied AG013 in Subjects with Locally Advanced Head and Neck Cancer Receiving Induction Chemotherapy. Cancer 2013, 119, 4268–4276. [Google Scholar] [CrossRef]
- Sharma, A.; Rath, G.K.; Chaudhary, S.P.; Thakar, A.; Mohanti, B.K.; Bahadur, S. Lactobacillus Brevis CD2 Lozenges Reduce Radiation- and Chemotherapy-Induced Mucositis in Patients with Head and Neck Cancer: A Randomized Double-Blind Placebo-Controlled Study. Eur. J. Cancer 2012, 48, 875–881. [Google Scholar] [CrossRef] [PubMed]
- Mirza, M.A.; Aruna, D.; Irukulla, M. Efficacy of Bacillus Clausii UBBC—07 Spores in the Amelioration of Oral Mucositis in Head and Neck Cancer Patients Undergoing Radiation Therapy. Cancer Treat. Res. Commun. 2022, 31, 100523. [Google Scholar] [CrossRef]
- Manifar, S.; Koopaie, M.; Jahromi, Z.M.; Kolahdooz, S. Effect of Synbiotic Mouthwash on Oral Mucositis Induced by Radiotherapy in Oral Cancer Patients: A Double-Blind Randomized Clinical Trial. Support. Care Cancer 2023, 31, 31. [Google Scholar] [CrossRef]
- Xia, C.; Jiang, C.; Li, W.; Wei, J.; Hong, H.; Li, J.; Feng, L.; Wei, H.; Xin, H.; Chen, T. A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma. Front. Immunol. 2021, 12, 618150. [Google Scholar] [CrossRef]
- Doppalapudi, R.; Vundavalli, S.; Prabhat, M. Effect of Probiotic Bacteria on Oral Candida in Head- And Neck-Radiotherapy Patients: A Randomized Clinical Trial. J. Cancer Res. Ther. 2020, 16, 470–477. [Google Scholar] [CrossRef]
- Vesty, A.; Gear, K.; Boutell, S.; Taylor, M.W.; Douglas, R.G.; Biswas, K. Randomised, Double-Blind, Placebo-Controlled Trial of Oral Probiotic Streptococcus Salivarius M18 on Head and Neck Cancer Patients Post-Radiotherapy: A Pilot Study. Sci. Rep. 2020, 10, 13201. [Google Scholar] [CrossRef]
- McGuinness, L.A.; Higgins, J.P. Risk-of-Bias VISualization (Robvis): An R Package and Shiny Web App for Visualizing Risk-of-Bias Assessments. Res. Syn. Meth. 2020, 12, 55–61. [Google Scholar] [CrossRef]
- Snydman, D.R. The Safety of Probiotics. Proc. Clin. Infect. Dis. 2008, 46, S104–S111. [Google Scholar] [CrossRef] [PubMed]
- Vera-Llonch, M.; Oster, G.; Hagiwara, M.; Sonis, S. Oral Mucositis in Patients Undergoing Radiation Treatment for Head and Neck Carcinoma. Cancer 2006, 106, 329–336. [Google Scholar] [CrossRef] [PubMed]
- Sanguineti, G.; Sormani, M.P.; Marur, S.; Gunn, G.B.; Rao, N.; Cianchetti, M.; Ricchetti, F.; McNutt, T.; Wu, B.; Forastiere, A. Effect of Radiotherapy and Chemotherapy on the Risk of Mucositis during Intensity-Modulated Radiation Therapy for Oropharyngeal Cancer. Int. J. Radiat. Oncol. Biol. Phys. 2012, 8, 235–2423. [Google Scholar] [CrossRef]
- Zhu, X.X.; Yang, X.J.; Chao, Y.L.; Zheng, H.M.; Sheng, H.F.; Liu, H.Y.; He, Y.; Zhou, H.W. The Potential Effect of Oral Microbiota in the Prediction of Mucositis During Radiotherapy for Nasopharyngeal Carcinoma. EBioMedicine 2017, 18, 23–31. [Google Scholar] [CrossRef] [PubMed]
- Gugnacki, P.; Sierko, E. Is There an Interplay between Oral Microbiome, Head and Neck Carcinoma and Radiation-Induced Oral Mucositis? Cancers 2021, 13, 5902. [Google Scholar] [CrossRef]
- Ye, Y.; Carlsson, G.; Agholme, M.B.; Wilson, J.A.L.; Roos, A.; Henriques-Normark, B.; Engstrand, L.; Modéer, T.; Pütsep, K. Oral Bacterial Community Dynamics in Paediatric Patients with Malignancies in Relation to Chemotherapy-Related Oral Mucositis: A Prospective Study. Clin. Microbiol. Infect. 2013, 19, E559–E567. [Google Scholar] [CrossRef]
- Gupta, N.; Ferreira, J.; Hong, C.H.L.; Tan, K.S. Lactobacillus Reuteri DSM 17938 and ATCC PTA 5289 Ameliorates Chemotherapy-Induced Oral Mucositis. Sci. Rep. 2020, 10, 16189. [Google Scholar] [CrossRef]
- Lalla, R.V.; Latortue, M.C.; Hong, C.H.; Ariyawardana, A.; D’Amato-Palumbo, S.; Fischer, D.J.; Martof, A.; Nicolatou-Galitis, O.; Patton, L.L.; Elting, L.S.; et al. A Systematic Review of Oral Fungal Infections in Patients Receiving Cancer Therapy. Support. Care Cancer 2010, 18, 985–992. [Google Scholar] [CrossRef]
- Epstein, J.B.; Thariat, J.; Bensadoun, R.-J.; Barasch, A.; Murphy, B.A.; Kolnick, L.; Popplewell, L.; Maghami, E. Oral Complications of Cancer and Cancer Therapy. CA Cancer J. Clin. 2012, 62, 400–422. [Google Scholar] [CrossRef]
- Sardi, J.C.O.; Almeida, A.M.F.; Mendes Giannini, M.J.S. New Antimicrobial Therapies Used against Fungi Present in Subgingival Sites—A Brief Review. Arch. Oral Biol. 2011, 56, 951–959. [Google Scholar] [CrossRef]
- Jørgensen, M.R.; Kragelund, C.; Jensen, P.Ø.; Keller, M.K.; Twetman, S. Probiotic Lactobacillus Reuteri Has Antifungal Effects on Oral Candida Species in Vitro. J. Oral Microbiol. 2017, 9, 1274582. [Google Scholar] [CrossRef] [PubMed]
- Ishikawa, K.H.; Mayer, M.P.A.; Miyazima, T.Y.; Matsubara, V.H.; Silva, E.G.; Paula, C.R.; Campos, T.T.; Nakamae, A.E.M. A Multispecies Probiotic Reduces Oral Candida Colonization in Denture Wearers. J. Prosthodont. 2015, 24, 194–199. [Google Scholar] [CrossRef]
- Keller, M.K.; Kragelund, C. Randomized Pilot Study on Probiotic Effects on Recurrent Candidiasis in Oral Lichen Planus Patients. Oral. Dis. 2018, 24, 1107–1114. [Google Scholar] [CrossRef] [PubMed]
- Hatakka, K.; Ahola, A.J.; Yli-Knuuttila, H.; Richardson, M.; Poussa, T.; Meurman, J.H.; Korpela, R. Probiotics Reduce the Prevalence of Oral Candida in the Elderly a Randomized Controlled Trial. J. Dent. Res. 2007, 86, 125–130. [Google Scholar] [CrossRef] [PubMed]
- Minić, I.; Pejčić, A.; Bradić-Vasić, M. Effect of the Local Probiotics in the Therapy of Periodontitis A Randomized Prospective Study. Int. J. Dent. Hyg. 2022, 20, 401–407. [Google Scholar] [CrossRef]
- Teughels, W.; Durukan, A.; Ozcelik, O.; Pauwels, M.; Quirynen, M.; Haytac, M.C. Clinical and Microbiological Effects of Lactobacillus Reuteri Probiotics in the Treatment of Chronic Periodontitis: A Randomized Placebo-Controlled Study. J. Clin. Periodontol. 2013, 40, 1025–1035. [Google Scholar] [CrossRef]
- Invernici, M.M.; Salvador, S.L.; Silva, P.H.F.; Soares, M.S.M.; Casarin, R.; Palioto, D.B.; Souza, S.L.S.; Taba, M.; Novaes, A.B.; Furlaneto, F.A.C.; et al. Effects of Bifidobacterium Probiotic on the Treatment of Chronic Periodontitis: A Randomized Clinical Trial. J. Clin. Periodontol. 2018, 45, 1198–1210. [Google Scholar] [CrossRef]
- Kang, M.S.; Lee, D.S.; Lee, S.A.; Kim, M.S.; Nam, S.H. Effects of Probiotic Bacterium Weissella Cibaria CMU on Periodontal Health and Microbiota: A Randomised, Double-Blind, Placebo-Controlled Trial. BMC Oral Health 2020, 20, 243. [Google Scholar] [CrossRef]
- Montero, E.; Iniesta, M.; Rodrigo, M.; Marín, M.J.; Figuero, E.; Herrera, D.; Sanz, M. Clinical and Microbiological Effects of the Adjunctive Use of Probiotics in the Treatment of Gingivitis: A Randomized Controlled Clinical Trial. J. Clin. Periodontol. 2017, 44, 708–716. [Google Scholar] [CrossRef]
- Pudgar, P.; Povšič, K.; Čuk, K.; Seme, K.; Petelin, M.; Gašperšič, R. Probiotic Strains of Lactobacillus Brevis and Lactobacillus Plantarum as Adjunct to Non-Surgical Periodontal Therapy: 3-Month Results of a Randomized Controlled Clinical Trial. Clin. Oral Investig. 2021, 25, 1411–1422. [Google Scholar] [CrossRef]
- Pelekos, G.; Ho, S.N.; Acharya, A.; Leung, W.K.; McGrath, C. A Double-Blind, Paralleled-Arm, Placebo-Controlled and Randomized Clinical Trial of the Effectiveness of Probiotics as an Adjunct in Periodontal Care. J. Clin. Periodontol. 2019, 46, 1217–1227. [Google Scholar] [CrossRef] [PubMed]
Author, Year, Country | Study Design | Participants/Treatment | Probiotic Intervention | Evaluation/Outcome |
---|---|---|---|---|
de Sanctis et al., 2019, Italy [22] | Phase III RCT, open-label, multicentre | n = 68; age ≥ 18; 1:1 allocation; chemoradiotherapy or biological agent + RT | L. brevis CD2 (2 × 109 CFU, 6 lozenges/day from day 1 of RT to 1 week after); control: sodium bicarbonate mouthwash | No benefit of L. brevis CD2 in reducing severe OM |
Jiang et al., 2019, China [23] | RCT, double-blind, placebo-controlled | n = 99; age 18–70; 2:1 allocation; CCRT for nasopharyngeal carcinoma | B. longum, L. lactis, E. faecium (3 capsules/day during treatment); control: placebo | Significant reduction in OM incidence |
Limaye et al., 2013, USA [24] | RCT, single-blind, placebo-controlled | n = 25; mean age 54; 5:2 allocation; induction chemotherapy | AG013 mouthwash (L. lactis recombinant); 1/3/6 times daily, days 1–14 of cycle 2 (induction QT) | 35% decrease in OM days in probiotic group |
Sharma et al., 2012, India [25] | RCT, double-blind, placebo-controlled | n = 200; mean age 50; 1:1 allocation; chemoradiotherapy | L. brevis CD2 (2 × 109 CFU, 6 lozenges/day); from day 1 to 1-week post-treatment | Significant reduction in grade III–IV OM |
Mirza et al., 2022, India [26] | RCT, double-blind, placebo-controlled | n = 46; age 30–60; 1:1 allocation; radiotherapy | Bacillus clausii (2 × 109 spores, oral suspension, twice/day for 30 days); control: placebo | Grade ≥ 3 OM: 33% (probiotic) vs. 67% (placebo) |
Doppalapudi et al., 2020, India [29] | RCT, 3-arm trial | n = 86; age 24–80; radiotherapy | L. acidophilus, L. rhamnosus, B. longum, S. boulardii; probiotic sachets 3×/day, 30 days; control: antifungal, probiotics and antifungals | Reduction in C. albicans in probiotic and combo groups |
Vesty et al., 2020, New Zealand [30] | RCT, double-blind, placebo-controlled (pilot) | n = 13; age 40–70; 1:1 allocation; radiotherapy | S. salivarius M18 (3.5 × 109 CFU, 1 lozenge/day for 4 weeks) | No significant change in microbiota; slight improvement in periodontal scores |
Manifar et al., 2023, Iran [27] | RCT, double-blind, placebo-controlled | n = 64; age 20–70; 1:1 allocation; IMRT | Symbiotic mouthwash (Bifidobacterium, Lactobacillus, Streptococcus + prebiotic); 3×/day; day from 1 of RT to 1 week after | Significant reduction in OM severity |
Xia et al., 2021, China [28] | Phase II RCT, placebo-controlled | n = 77; age 18–70; 1:1 allocation; CCRT | Modified strains: L. plantarum, B. animalis, L. rhamnosus, L. acidophilus; (1 capsule/day, during treatment) | Reduction in OM severity; improved immunity and microbiota balance |
Author, Year, Country | Evaluation Focus | Key Results |
---|---|---|
Jiang et al., 2019, China [23] | Effect of probiotics on oral mucositis | Significant reduction in grades 2–3 OM (p < 0.0001) |
Sharma et al., 2012, India [25] | Effect of probiotics on oral mucositis | Reduced incidence of grade 3–4 OM (p = 0.001) |
Limaye et al., 2013, USA [24] | Effect of probiotics on oral mucositis | 35% reduction in OM days in probiotic group |
de Sanctis et al., 2019, Italy [22] | Effect of probiotics on oral mucositis | No significant difference (p = 0.974) |
Mirza et al., 2022, India [26] | Effect of probiotics on oral mucositis | Reduced grade ≥ 3 OM: 43% vs. 68%; p < 0.05 |
Manifar et al., 2023, Iran [27] | Effect of probiotics on oral mucositis | Significant reduction in grade 3 OM (p < 0.001) |
Xia et al., 2021, China [28] | Effect of probiotics on oral mucositis | Lower OM severity across all grades (p < 0.01) |
Doppalapudi et al., 2020, India [29] | Effect on oral candidiasis | Reduced Candida counts in probiotic and combination groups (p < 0.01) |
Vesty et al., 2020, New Zealand [30] | Effect on periodontal status and microbiota | No significant change in plaque or CPITN; microbiota remained stable (p > 0.05) |
Jiang et al., 2019, China [23] | Effect on gut microbiota | Probiotic group showed restored diversity, similar to healthy controls |
Xia et al., 2021, China [28] | Effect on gut microbiota | Improved microbial balance post-probiotic intervention |
Subgroup Category | Number of Studies | Comment |
---|---|---|
Radiotherapy only | 4 | Heterogeneous probiotic formulations |
Chemoradiotherapy | 3 | Different treatment protocols and dosing schedules |
Probiotics containing L. brevis | 2 | Differences in clinical context, treatment protocols, and timing of administration |
High risk of bias | 5 | Issues with allocation concealment and reporting consistency |
Low risk of bias | 2 | Consistent results; both included in the meta-analysis |
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Pereira-Riveros, T.; Jané-Salas, E.; López-López, J.; Saka-Herran, C.; Linares-Galiana, I.; Vinuesa-Aumedes, T. Probiotics and Oral Complications of Antineoplastic Therapy in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Dent. J. 2025, 13, 254. https://doi.org/10.3390/dj13060254
Pereira-Riveros T, Jané-Salas E, López-López J, Saka-Herran C, Linares-Galiana I, Vinuesa-Aumedes T. Probiotics and Oral Complications of Antineoplastic Therapy in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Dentistry Journal. 2025; 13(6):254. https://doi.org/10.3390/dj13060254
Chicago/Turabian StylePereira-Riveros, Tanya, Enric Jané-Salas, José López-López, Constanza Saka-Herran, Isabel Linares-Galiana, and Teresa Vinuesa-Aumedes. 2025. "Probiotics and Oral Complications of Antineoplastic Therapy in Head and Neck Cancer: A Systematic Review and Meta-Analysis" Dentistry Journal 13, no. 6: 254. https://doi.org/10.3390/dj13060254
APA StylePereira-Riveros, T., Jané-Salas, E., López-López, J., Saka-Herran, C., Linares-Galiana, I., & Vinuesa-Aumedes, T. (2025). Probiotics and Oral Complications of Antineoplastic Therapy in Head and Neck Cancer: A Systematic Review and Meta-Analysis. Dentistry Journal, 13(6), 254. https://doi.org/10.3390/dj13060254