Assessment of the Effect of Probiotic Supplementation on Proinflammatory Mechanisms Induced by Systemic Treatment in Women With Breast Cancer

NCT07607548 | Completed

• 1 other identifier: 551/22
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The gut microbiota and its role in cancer treatment are currently the subject of intensive research. It has long been known that interactions between the microbiome and the host are responsible for the proper functioning of many physiological processes and for maintaining systemic homeostasis. Although the precise mechanisms underlying these interactions remain unclear, they appear to have a significant impact on the development and treatment of various diseases, including cancer. One of the crucial functions regulated by the gut microbiota is the body's immune response. The appropriate quantitative and qualitative composition of the gut microbiota supports the maintenance of a critical balance between pro- and anti-inflammatory processes. Even a slight disruption of this balance can lead to systemic metabolic and biochemical changes, affecting the overall condition of the body and its systems. Chemotherapy and immunotherapy are standard treatment protocols for cancer patients, including those with breast cancer. Despite their proven role in prolonging remission and improving patient survival, their effectiveness remains limited. Regardless of the regimen, the use of cytotoxic drugs does not fully prevent metastasis. In women with breast cancer, the risk of local recurrence or distant metastasis-primarily to the bones, lungs, and liver-is approximately 30% and increases over time following the initial diagnosis. Although the risk of cancer recurrence in this group is largely influenced by the baseline characteristics of the tumor, increasing attention is being paid to the immune response to treatment. The effectiveness of anticancer therapies depends not only on the response of cancer cells but also on the condition of the entire organism, particularly the host's immune system. Recent studies indicate that chemotherapy induces a systemic inflammatory state that may persist long after treatment completion. Prolonged inflammation, along with increased levels of chemoattractants, cytokines, and metalloproteinases, creates an environment conducive to cancer progression and metastasis. Therefore, it is increasingly suggested that chemotherapy-induced chronic inflammation may be a significant factor limiting therapeutic effectiveness. Although the precise mechanisms underlying inflammation during chemotherapy are not fully understood, a growing body of evidence points to a key role of the gut microbiota in this process. Cytotoxic drugs used during chemotherapy disrupt both the quantitative and qualitative composition of the gut microbiota, leading to dysbiosis. Dysbiosis is associated with the overgrowth of pathogenic species and alterations in the profile of microbial metabolites, often favoring those that negatively affect the intestinal barrier. Consequently, inflammation of the intestinal mucosa and increased intestinal permeability are observed during chemotherapy. Bacterial components, collectively known as pathogen-associated molecular patterns (PAMPs), can enter the bloodstream through the compromised intestinal barrier, triggering immune cell activation and systemic inflammation. An important link between the gut microbiota and progressive inflammation involves Toll-like receptors (TLRs), particularly TLR4, which is expressed on the surface of monocytes and recognizes, among other ligands, lipopolysaccharide (LPS) produced by Gram-negative bacteria. This interaction activates transcription factors such as Nuclear factor-κB (NF-κB), leading to the expression of genes involved in the immune response, including pro-inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and Cyclooxygenase-2 (COX-2). These cytokines promote tumor progression and metastasis both directly, by acting on cancer cells, and indirectly, by enhancing cell proliferation and angiogenesis. Several studies have reported increased expression and activity of TLR4 in various types of cancer, including breast cancer. Animal model studies have shown that blocking TLR4 reduces tumor metastasis and significantly decreases invasiveness. Therefore, inhibition of TLR4 signaling appears to be a promising therapeutic strategy for counteracting metastasis and chemoresistance. Probiotic therapy may contribute to this effect, as it has been shown to downregulate TLR4 expression and reduce levels of pro-tumor inflammatory mediators. The aim of this study is to evaluate the impact of probiotic therapy on immunological, biochemical, morphological, and anthropometric parameters in a group of women with breast cancer undergoing chemotherapy or immunotherapy. The study will include two visits: one before treatment initiation and another eight weeks later. The main hypothesis is that probiotic supplementation will reduce inflammation associated with systemic breast cancer treatment.

Conditions

Breast Cancer; Probiotic Therapy

Keywords

systemic treatment; inflammation

Outcome Measures

Primary Outcomes (5)

• Changes in serum levels of Tumor Necrosis Factor α (TNFα)

  Baseline, 8 week

• Changes in serum levels of interleukin-6 (IL-6)

  Baseline, 8 week

• Changes in serum levels of high-specific C-reactive protein (hsCRP)

  Baseline, 8 week

• Changes in Toll-like receptor 4 (TLR) expression on the surface of monocytes

  Baseline, 8 week

• Changes in the intracellular expression of cyclooxygenase 2 (COX-2)

  Baseline, 8 week

Secondary Outcomes (17)

• Changes in the concentration of lymphocytes

  Baseline, 8 week

• Changes in the concentration of leukocytes

  Baseline, 8 week

• Changes in the concentration of monocytes

  Baseline, 8 week

• Changes in the concentration of neutrophils

  Baseline, 8 week

• Changes in the concentration of erythrocytes

  Baseline, 8 week

Study Arms (2)

Probiotic supplementation

EXPERIMENTAL

Dietary Supplement: Probiotic

Placebo supplementation

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Probiotic DIETARY_SUPPLEMENT

The probiotic contained the Lactiplantibacillus plantarum 299v. It was prepared by Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland; probiotic capsules manufacturer - Institute Rosell-Lallemand, Montreal, Canada; Lactiplantibacillus plantarum 299v strain owner - Probi AB, Lund, Sweden. Placebo supplementation began on the day of chemotherapy initiation, according to the following regimen: 1 capsule/day in the first week (1 x 1010 colony-forming unit (CFU)), and 2 capsules/day in the following weeks (2 x 1010 CFU). The supplementation period lasted eight weeks.

Probiotic supplementation

Placebo DIETARY_SUPPLEMENT

The placebo contained crystalline cellulose powder. It was prepared by Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland.. Placebo supplementation began on the day of chemotherapy initiation and lasted eight weeks.

Placebo supplementation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• first-time chemotherapy
• written consent to participate in the research
• no antibiotic and probiotic therapy in the last 3 months

You may not qualify if:

• serious comorbidities (chronic renal failure, diabetes, autoimmune diseasese, unstable coronary artery disease or other cancers)
• previous history of cancer
• smoking cigarettes or using other stimulants
• another probiotic supplementation
• qualification for another type of treatment - surgery or hormone therapy

Sponsors & Collaborators

• Poznan University of Medical Sciences: lead
• Sanprobi Sp. z o.o., Sp. k., Szczecin, Poland: collaborator

Study Sites (1)

Greater Poland Cancer Centre

Poznan, 61-866, Poland

Location

Related Publications (19)

• Yang X, Fu Y, Liu J, Ren HY. Impact of probiotics on toll-like receptor 4 expression in an experimental model of ulcerative colitis. J Huazhong Univ Sci Technolog Med Sci. 2013 Oct;33(5):661-665. doi: 10.1007/s11596-013-1177-9. Epub 2013 Oct 20.

  PMID: 24142717 BACKGROUND

• Khademalhosseini M, Arababadi MK. Toll-like receptor 4 and breast cancer: an updated systematic review. Breast Cancer. 2019 May;26(3):265-271. doi: 10.1007/s12282-018-00935-2. Epub 2018 Dec 12.

  PMID: 30543015 BACKGROUND

• Ahmed A, Redmond HP, Wang JH. Links between Toll-like receptor 4 and breast cancer. Oncoimmunology. 2013 Feb 1;2(2):e22945. doi: 10.4161/onci.22945.

  PMID: 23526132 BACKGROUND

• Yiu JH, Dorweiler B, Woo CW. Interaction between gut microbiota and toll-like receptor: from immunity to metabolism. J Mol Med (Berl). 2017 Jan;95(1):13-20. doi: 10.1007/s00109-016-1474-4. Epub 2016 Sep 17.

  PMID: 27639584 BACKGROUND

• Velloso LA, Folli F, Saad MJ. TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation. Endocr Rev. 2015 Jun;36(3):245-71. doi: 10.1210/er.2014-1100. Epub 2015 Mar 26.

  PMID: 25811237 BACKGROUND

• Ge Y, Wang X, Guo Y, Yan J, Abuduwaili A, Aximujiang K, Yan J, Wu M. Gut microbiota influence tumor development and Alter interactions with the human immune system. J Exp Clin Cancer Res. 2021 Jan 25;40(1):42. doi: 10.1186/s13046-021-01845-6.

  PMID: 33494784 BACKGROUND

• Secombe KR, Coller JK, Gibson RJ, Wardill HR, Bowen JM. The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy-induced gastrointestinal toxicity. Int J Cancer. 2019 May 15;144(10):2365-2376. doi: 10.1002/ijc.31836. Epub 2018 Oct 1.

  PMID: 30155890 BACKGROUND

• Montassier E, Gastinne T, Vangay P, Al-Ghalith GA, Bruley des Varannes S, Massart S, Moreau P, Potel G, de La Cochetiere MF, Batard E, Knights D. Chemotherapy-driven dysbiosis in the intestinal microbiome. Aliment Pharmacol Ther. 2015 Sep;42(5):515-28. doi: 10.1111/apt.13302. Epub 2015 Jul 6.

  PMID: 26147207 BACKGROUND

• Wei L, Wen XS, Xian CJ. Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways. Int J Mol Sci. 2021 Aug 31;22(17):9474. doi: 10.3390/ijms22179474.

  PMID: 34502383 BACKGROUND

• Oh B, Boyle F, Pavlakis N, Clarke S, Guminski A, Eade T, Lamoury G, Carroll S, Morgia M, Kneebone A, Hruby G, Stevens M, Liu W, Corless B, Molloy M, Libermann T, Rosenthal D, Back M. Emerging Evidence of the Gut Microbiome in Chemotherapy: A Clinical Review. Front Oncol. 2021 Sep 16;11:706331. doi: 10.3389/fonc.2021.706331. eCollection 2021.

  PMID: 34604043 BACKGROUND

• Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020 Jun;30(6):492-506. doi: 10.1038/s41422-020-0332-7. Epub 2020 May 20.

  PMID: 32433595 BACKGROUND

• Lee KA, Luong MK, Shaw H, Nathan P, Bataille V, Spector TD. The gut microbiome: what the oncologist ought to know. Br J Cancer. 2021 Oct;125(9):1197-1209. doi: 10.1038/s41416-021-01467-x. Epub 2021 Jul 14.

  PMID: 34262150 BACKGROUND

• Cheng WY, Wu CY, Yu J. The role of gut microbiota in cancer treatment: friend or foe? Gut. 2020 Oct;69(10):1867-1876. doi: 10.1136/gutjnl-2020-321153. Epub 2020 Aug 5.

  PMID: 32759302 BACKGROUND

• Edwardson DW, Boudreau J, Mapletoft J, Lanner C, Kovala AT, Parissenti AM. Inflammatory cytokine production in tumor cells upon chemotherapy drug exposure or upon selection for drug resistance. PLoS One. 2017 Sep 15;12(9):e0183662. doi: 10.1371/journal.pone.0183662. eCollection 2017.

  PMID: 28915246 BACKGROUND

• Xu MM, Pu Y, Zhang Y, Fu YX. The Role of Adaptive Immunity in the Efficacy of Targeted Cancer Therapies. Trends Immunol. 2016 Feb;37(2):141-153. doi: 10.1016/j.it.2015.12.007. Epub 2016 Jan 7.

  PMID: 26778079 BACKGROUND

• Brown T, Sykes D, Allen AR. Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System. Biomedicines. 2021 Feb 13;9(2):189. doi: 10.3390/biomedicines9020189.

  PMID: 33668580 BACKGROUND

• Gartung A, Yang J, Sukhatme VP, Bielenberg DR, Fernandes D, Chang J, Schmidt BA, Hwang SH, Zurakowski D, Huang S, Kieran MW, Hammock BD, Panigrahy D. Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2/sEH inhibitor. Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1698-1703. doi: 10.1073/pnas.1803999116. Epub 2019 Jan 15.

  PMID: 30647111 BACKGROUND

• Cheung YT, Ng T, Shwe M, Ho HK, Foo KM, Cham MT, Lee JA, Fan G, Tan YP, Yong WS, Madhukumar P, Loo SK, Ang SF, Wong M, Chay WY, Ooi WS, Dent RA, Yap YS, Ng R, Chan A. Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study. Ann Oncol. 2015 Jul;26(7):1446-51. doi: 10.1093/annonc/mdv206. Epub 2015 Apr 28.

  PMID: 25922060 BACKGROUND

• Grant CV, Loman BR, Bailey MT, Pyter LM. Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice. Brain Behav Immun. 2021 Jul;95:401-412. doi: 10.1016/j.bbi.2021.04.014. Epub 2021 Apr 22.

  PMID: 33895287 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms; Inflammation

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: May 26, 2026
• Study Start: October 18, 2022
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: May 26, 2026

Record last verified: 2026-02

Locations

PL (1)