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BMC Complementary Medicine and Therapies

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Open Access 01-12-2023 | Breast Cancer | Research

The effects of synbiotics supplementation on reducing chemotherapy-induced side effects in women with breast cancer: a randomized placebo-controlled double-blind clinical trial

Authors: Yasaman Khazaei, Ali Basi, Maria Luz Fernandez, Hossein Foudazi, Rafat Bagherzadeh, Farzad Shidfar

Published in: BMC Complementary Medicine and Therapies | Issue 1/2023

Abstract

Background

The prevalence of breast cancer and its mortality rate are increasing rapidly among women worldwide. On other hand, the courses of chemotherapy as the main treatment for these patients are too much exhaustive and annoying. This study was designed to evaluate the use of synbiotics (probiotics + prebiotics) supplementation as a safe and inexpensive adjuvant treatment in reducing common chemotherapy side effects in women with breast cancer.

Methods

The current study was conducted on 67 women with definitive diagnosis of breast cancer who were hospitalized to receive one-day chemotherapy sessions, and met the inclusion criteria. The patients were randomly allocated to the intervention or control group to receive synbiotics or placebo, respectively. They received oral consumption of synbiotics supplements twice a day for 8 weeks. The primary outcome was the changes in severity or experience of chemotherapy complication, analyzed by intention to treat (ITT). The instruments included 7 validated questionnaires which were used to assess chemotherapy complications in the initiation, 4 weeks and 8 weeks after intervention. Dietary intake was measured by 24-h dietary recall at the beginning, week 4 and week 8. Data were analyzed by SPSS software version 24. P-value < 0.05 was considered as statistically significant.

Results

67 breast cancer patients participated in the study. 8 weeks after intervention and adjusting the confounders, the severity of chemotherapy complications including unnormal defecation (P = 0.005) and fatigue (P < 0/001) decreased significantly in the synbiotics group compared to the placebo group. Furthermore, nausea/vomiting (P = 0.015), and anorexia (P < 0.001) were decreased at the end of the study compared to the first visit, but it was not statistically significant compared to the placebo group.

Conclusions

Synbiotics supplementation during chemotherapy can potentially reduce the severity of fatigue and abnormal defecation. It can help reduce anorexia and nausea/vomiting.

Trial Registration

This study was registered in the Iranian Registry of Clinical Trials (IRCT) (registered code: IRCT20091114002709N56) (date of registration: 5/5/2021). Direct link to the trial page: https://www.irct.ir/trial/54559.

Hajji-Louati M, Cordina-Duverger E, Laouali N, Mancini F-R, Guénel P. A case–control study in France showing that a pro-inflammatory diet is associated with a higher risk of breast cancer. Sci Rep. 2021;11(1):1–10.CrossRef

Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A, Breast, Cancer—Epidemiology. Risk factors, classification, prognostic markers, and current treatment Strategies—An. Updated Rev Cancers. 2021;13(17):4287.

Isfahani P, Arefy M, Shamsaii M. Prevalence of severe depression in iranian women with breast cancer: a meta-analysis. Depression research and treatment. 2020;2020.

Iacoviello L, Bonaccio M, de Gaetano G, Donati MB, editors. Epidemiology of breast cancer, a paradigm of the common soil hypothesis. Seminars in cancer biology. Elsevier; 2021.

Kazemi A, Barati-Boldaji R, Soltani S, Mohammadipoor N, Esmaeilinezhad Z, Clark CC, et al. Intake of various food groups and risk of breast cancer: a systematic review and dose-response meta-analysis of prospective studies. Adv Nutr. 2021;12(3):809–49.PubMedCrossRef

Sadeghian M, Rahmani S, Khalesi S, Hejazi E. A review of fasting effects on the response of cancer to chemotherapy. Clin Nutr. 2021;40(4):1669–81.PubMedCrossRef

van den Berg MM, Kok DE, Posthuma L, Kamps L, Kelfkens CS, Buist N, et al. Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I–IIIB breast cancer receiving chemotherapy. Breast Cancer Res Treat. 2019;173(2):475–81.PubMedCrossRef

Rodriguez-Arrastia M, Martinez-Ortigosa A, Rueda-Ruzafa L, Folch Ayora A, Ropero-Padilla C. Probiotic supplements on oncology patients’ treatment-related side effects: a systematic review of randomized controlled trials. Int J Environ Res Public Health. 2021;18(8):4265.PubMedPubMedCentralCrossRef

Mego M, Holec V, Drgona L, Hainova K, Ciernikova S, Zajac V. Probiotic bacteria in cancer patients undergoing chemotherapy and radiation therapy. Complement Ther Med. 2013;21(6):712–23.PubMedCrossRef

10.

Dos Reis SA, da Conceição LL, Siqueira NP, Rosa DD, da Silva LL. Maria do Carmo GP. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res. 2017;37:1–19.PubMedCrossRef

11.

Golkhalkhali B, Rajandram R, Paliany AS, Ho GF, Wan Ishak WZ, Johari CS, et al. Strain-specific probiotic (microbial cell preparation) and omega‐3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial. Asia‐Pacific J Clin Oncol. 2018;14(3):179–91.CrossRef

12.

Lee J-Y, Chu S-H, Jeon JY, Lee M-K, Park J-H, Lee D-C, et al. Effects of 12 weeks of probiotic supplementation on quality of life in colorectal cancer survivors: a double-blind, randomized, placebo-controlled trial. Dig Liver Disease. 2014;46(12):1126–32.CrossRef

13.

Reyna-Figueroa J, Barrón-Calvillo E, García-Parra C, Galindo-Delgado P, Contreras-Ochoa C, Lagunas-Martínez A, et al. Probiotic supplementation decreases chemotherapy-induced gastrointestinal side effects in patients with acute leukemia. J Pediatr Hematol Oncol. 2019;41(6):468–72.PubMedCrossRef

14.

Lages PC, Generoso SV, Correia MIT. Postoperative symbiotic in patients with head and neck cancer: a double-blind randomised trial. Br J Nutr. 2018;119(2):190–5.PubMedCrossRef

15.

Status WP. The use and interpretation of anthropometry: report of a World Health Organization (WHO) expert committee. Geneva, Switzerland: World Health Organization; 1995.

16.

Aadahl M, Jørgensen T. Validation of a new self-report instrument for measuring physical activity. Med Sci Sports Exerc. 2003;35(7):1196–202.PubMedCrossRef

17.

Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920–4.PubMedCrossRef

18.

Rhodes VA, Watson PM, Johnson MH, editors. Association of chemotherapy related nausea and vomiting with pretreatment anxiety. Oncology Nursing Forum; 1986.

19.

Haghighat S, Akbari ME, Holakouei K, Rahimi A, Montazeri A. Factors predicting fatigue in breast cancer patients. Support Care Cancer. 2003;11(8):533–8.PubMedCrossRef

20.

Momayyezi M, Fallahzadeh H, Farzaneh F, Momayyezi M. Iranian version of cancer-related fatigue questionnaire: construction and validation. Zahedan J Res Med Sci. 2018;20(12).

21.

Bandani-Susan B, Montazeri A, Haghighizadeh MH, Araban M. The effect of mobile health educational intervention on body image and fatigue in breast cancer survivors: a randomized controlled trial. Ir J Med Sci (1971-). 2021:1–7.

22.

Tabrizi FM, Alizadeh S. Cancer related fatigue in breast cancer survivors: in correlation to demographic factors. Maedica. 2017;12(2):106.PubMedPubMedCentral

23.

Khosravi M, Sadighi S, Moradi S, Zendehdel K. Persian-McGill pain questionnaire; translation, adaptation and reliability in cancer patients: a brief report. Tehran Univ Med J. 2013;71(1).

24.

Goudarzian AH, Jafari A, Beik S, Bagheri Nesami M. Are religious coping and pain perception related together? Assessment in iranian cancer patients. J Relig Health. 2018;57(6):2108–17.PubMedCrossRef

25.

Gelhorn HL, Gries KS, Speck RM, Duus EM, Bourne RK, Aggarwal D, et al. Comprehensive validation of the functional assessment of anorexia/cachexia therapy (FAACT) anorexia/cachexia subscale (A/CS) in lung cancer patients with involuntary weight loss. Qual Life Res. 2019;28(6):1641–53.PubMedCrossRef

26.

Blauwhoff-Buskermolen S, Ruijgrok C, Ostelo RW, de Vet HC, Verheul HM, de van der Schueren MA, et al. The assessment of anorexia in patients with cancer: cut-off values for the FAACT–A/CS and the VAS for appetite. Support Care Cancer. 2016;24(2):661–6.PubMedCrossRef

27.

Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.PubMedCrossRef

28.

Farrahi Moghaddam J, Nakhaee N, Sheibani V, Garrusi B, Amirkafi A. Reliability and validity of the Persian version of the Pittsburgh Sleep Quality Index (PSQI-P). Sleep and Breathing. 2012;16(1):79–82.PubMedCrossRef

29.

Abdali N, Nobahar M, Ghorbani R. Evaluation of emotional intelligence, sleep quality, and fatigue among iranian medical, nursing, and paramedical students: a cross-sectional study. Qatar Med J. 2020;2019(3):15.CrossRef

30.

Dadfar M, Kalibatseva Z, Lester D. Reliability and validity of the Farsi version of the Patient Health Questionnaire-9 (PHQ-9) with iranian psychiatric outpatients. Trends in Psychiatry and Psychotherapy. 2018;40:144–51.PubMedCrossRef

31.

Khamseh ME, Baradaran HR, Javanbakht A, Mirghorbani M, Yadollahi Z, Malek M. Comparison of the CES-D and PHQ-9 depression scales in people with type 2 diabetes in Tehran, Iran. BMC Psychiatry. 2011;11(1):1–6.CrossRef

32.

Omani-Samani R, Maroufizadeh S, Almasi-Hashiani A, Amini P. Prevalence of depression and its determinant factors among infertile patients in Iran based on the PHQ-9. Middle East Fertility Society Journal. 2018;23(4):460–3.CrossRef

33.

Saneei Totmaj A, Haghighat S, Jaberzadeh S, Navaei M, Vafa S, Janani L, et al. The Effects of Synbiotic supplementation on serum anti-inflammatory factors in the survivors of breast Cancer with Lymphedema following a low calorie Diet: a Randomized, Double-Blind, clinical trial. Nutr Cancer. 2022;74(3):869–81.PubMedCrossRef

34.

Vafa S, Haghighat S, Janani L, Totmaj AS, Navaei M, Amirinejad A, et al. The effects of synbiotic supplementation on serum inflammatory markers and edema volume in breast cancer survivors with lymphedema. EXCLI J. 2020;19:1.PubMedPubMedCentral

35.

Vafa S, Zarrati M, Malakootinejad M, Totmaj AS, Zayeri F, Salehi M, et al. Calorie restriction and synbiotics effect on quality of life and edema reduction in breast cancer-related lymphedema, a clinical trial. The Breast. 2020;54:37–45.PubMedPubMedCentralCrossRef

36.

Eslami M, Yousefi B, Kokhaei P, Hemati M, Nejad ZR, Arabkari V, et al. Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol. 2019;234(10):17127–43.PubMedCrossRef

37.

Polakowski CB, Kato M, Preti VB, Schieferdecker MEM, Campos ACL. Impact of the preoperative use of synbiotics in colorectal cancer patients: a prospective, randomized, double-blind, placebo-controlled study. Nutrition. 2019;58:40–6.PubMedCrossRef

38.

Lu D, Yan J, Liu F, Ding P, Chen B, Lu Y, et al. Probiotics in preventing and treating chemotherapy-induced diarrhea: a meta-analysis. Asia Pac J Clin Nutr. 2019;28(4):701–10.PubMed

39.

Linn YH, Thu KK, Win NHH. Effect of Probiotics for the Prevention of Acute Radiation-Induced Diarrhoea among Cervical Cancer Patients: a Randomized double-blind placebo-controlled study. Probiotics and Antimicrobial Proteins. 2019;11(2):638–47.PubMedCrossRef

40.

Wardill HR, Van Sebille YZA, Ciorba MA, Bowen JM. Prophylactic probiotics for cancer therapy-induced diarrhoea: a meta-analysis. Curr Opin Support Palliat Care. 2018;12(2):187–97.PubMedCrossRef

41.

Kwon H, Chae SH, Jung HJ, Shin HM, Ban O-H, Yang J, et al. The effect of probiotics supplementation in postoperative cancer patients: a prospective pilot study. Annals of Surgical Treatment and Research. 2021;101(5):281–90.PubMedPubMedCentralCrossRef

42.

Liu J, Huang XE. Efficacy of Bifidobacterium tetragenous viable bacteria tablets for cancer patients with functional constipation. Asian Pac J cancer Prevention: APJCP. 2014;15(23):10241–4.CrossRef

43.

Du SX, Jia YR, Ren SQ, Gong XJ, Tang H, Wan-Shui W, et al. The protective effects of Bacillus licheniformis preparation on gastrointestinal disorders and inflammation induced by radiotherapy in pediatric patients with central nervous system tumor. Adv Med Sci. 2018;63(1):134–9.PubMedCrossRef

44.

Amitay EL, Carr PR, Gies A, Laetsch DC, Brenner H. Probiotic/synbiotic treatment and postoperative complications in colorectal cancer patients: systematic review and meta-analysis of randomized controlled trials. Clin Translational Gastroenterol. 2020;11(12).

45.

Araújo MM, Montalvão-Sousa TM, Teixeira PC, Figueiredo ACMG, Botelho PB. The effect of probiotics on postsurgical complications in patients with colorectal cancer: a systematic review and meta-analysis. Nutr Rev. 2023;81(5):493–510.PubMedCrossRef

46.

Chudzik A, Orzyłowska A, Rola R, Stanisz GJ, Probiotics. Prebiotics and Postbiotics on Mitigation of Depression Symptoms: Modulation of the Brain-Gut-Microbiome Axis. Biomolecules. 2021;11(7).

47.

Jordan KR, Loman BR, Bailey MT, Pyter LM. Gut microbiota-immune‐brain interactions in chemotherapy‐associated behavioral comorbidities. Cancer. 2018;124(20):3990–9.PubMedCrossRef

48.

Lee SH, Cho DY, Lee SH, Han KS, Yang SW, Kim JH, et al. A Randomized Clinical Trial of Synbiotics in Irritable Bowel Syndrome: dose-dependent Effects on gastrointestinal symptoms and fatigue. Korean J Family Med. 2019;40(1):2–8.CrossRef

49.

Roman P, Carrillo-Trabalón F, Sánchez-Labraca N, Cañadas F, Estévez AF, Cardona D. Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review. Beneficial Microbes. 2018;9(4):603–11.PubMedCrossRef

50.

Davoodabadi A, Rohani SH, Hajian A. Effects of the oral probiotics to control pain and stress disorders of cyclical mastalgia associated with fibrocystic breast changes; a randomised controlled trial. Int J Surg Open. 2021;33:100358.CrossRef

51.

Inglis JE, Lin P-J, Kerns SL, Kleckner IR, Kleckner AS, Castillo DA, et al. Nutritional interventions for treating cancer-related fatigue: a qualitative review. Nutr Cancer. 2019;71(1):21–40.PubMedPubMedCentralCrossRef

52.

Childs DS, Jatoi A. A hunger for hunger: a review of palliative therapies for cancer-associated anorexia. Annals of Palliative Medicine. 2019;8(1):50.PubMedCrossRef

53.

Ezeoke CC, Morley JE. Pathophysiology of anorexia in the cancer cachexia syndrome. J cachexia Sarcopenia Muscle. 2015;6(4):287–302.PubMedPubMedCentralCrossRef

54.

Yeom E, Yu K. Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia. Exp Mol Med. 2022;54(4):426–32.PubMedPubMedCentralCrossRef

55.

Anukam KC, Osazuwa EO, Reid G. Improved appetite of pregnant rats and increased birth weight of newborns following feeding with probiotic Lactobacillus rhamnosus GR-1 and L. fermentum RC-14. J Appl Res. 2005;5(1):46–52.

56.

Giorgia G, Elia C, Andrea P, Cinzia C, Stefania S, Ana R, et al. Effects of Lactogen 13, a new probiotic preparation, on gut microbiota and endocrine signals controlling growth and appetite of Oreochromis niloticus juveniles. Microb Ecol. 2018;76(4):1063–74.CrossRef

57.

Lutfi E, Basili D, Falcinelli S, Morillas L, Carnevali O, Capilla E, et al. The probiotic Lactobacillus rhamnosus mimics the dark-driven regulation of appetite markers and melatonin receptors’ expression in zebrafish (Danio rerio) larvae: understanding the role of the gut microbiome. Comp Biochem Physiol B: Biochem Mol Biol. 2021;256:110634.PubMedCrossRef

58.

An JM, Kang EA, Han Y-M, Oh JY, Lee DY, Choi SH, et al. Dietary intake of probiotic kimchi ameliorated IL-6-driven cancer cachexia. J Clin Biochem Nutr. 2019;65(2):109–17.PubMedPubMedCentralCrossRef

59.

Gröbner EM, Zeiler M, Fischmeister FPS, Kollndorfer K, Schmelz S, Schneider A, et al. The effects of probiotics administration on the gut microbiome in adolescents with anorexia nervosa—A study protocol for a longitudinal, double-blind, randomized, placebo‐controlled trial. Eur Eat Disorders Rev. 2022;30(1):61–74.CrossRef

60.

Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015:392.

61.

Kazemi A, Noorbala A, Djafarian K. Effect of probiotic and prebiotic versus placebo on appetite in patients with major depressive disorder: post hoc analysis of a randomised clinical trial. J Hum Nutr Dietetics. 2020;33(1):56–65.CrossRef

62.

Ali AM, Ali EM, Ahmed ME, Hendawy AO. Targeting gut microbiome and the recovery of muscle loss Associated with Cancer (Cachexia): an overview of the possible effect of Bee Products. Medico-legal Update. 2021;21(2).

63.

Bowen JM, Stringer AM, Gibson RJ, Yeoh AS, Hannam S, Keefe DM. VSL# 3 probiotic treatment reduces chemotherapy-induced diarrhoea and weight loss. Cancer Biol Ther. 2007;6(9):1445–50.CrossRef

64.

Yuan K-T, Yu H-L, Feng W-D, Chong P, Yang T, Xue C-L, et al. Bifidobacterium infantis has a beneficial effect on 5-fluorouracil-induced intestinal mucositis in rats. Beneficial Microbes. 2015;6(1):113–8.PubMedCrossRef

65.

Miknevicius P, Zulpaite R, Leber B, Strupas K, Stiegler P, Schemmer P. The impact of probiotics on intestinal mucositis during chemotherapy for colorectal cancer: a comprehensive review of animal studies. Int J Mol Sci. 2021;22(17):9347.PubMedPubMedCentralCrossRef

66.

Jiang C, Wang H, Xia C, Dong Q, Chen E, Qiu Y, 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(7):1081–90.PubMedCrossRef

67.

Tang Y, Wu Y, Huang Z, Dong W, Deng Y, Wang F, et al. Administration of probiotic mixture DM# 1 ameliorated 5-fluorouracil–induced intestinal mucositis and dysbiosis in rats. Nutrition. 2017;33:96–104.PubMedCrossRef

68.

Tian Y, Li M, Song W, Jiang R, Li YQ. Effects of probiotics on chemotherapy in patients with lung cancer. Oncol Lett. 2019;17(3):2836–48.PubMedPubMedCentral

Title: The effects of synbiotics supplementation on reducing chemotherapy-induced side effects in women with breast cancer: a randomized placebo-controlled double-blind clinical trial
Authors: Yasaman Khazaei
Ali Basi
Maria Luz Fernandez
Hossein Foudazi
Rafat Bagherzadeh
Farzad Shidfar
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Probiotics
Nausea
Vomiting
Published in: BMC Complementary Medicine and Therapies / Issue 1/2023
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-023-04165-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The effects of synbiotics supplementation on reducing chemotherapy-induced side effects in women with breast cancer: a randomized placebo-controlled double-blind clinical trial

Abstract

Background

Methods

Results

Conclusions

Trial Registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial Registration

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