Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Jakubauskas, M.
THE ROLE OF PROBIOTICS IN COLORECTAL CANCER LIVER METASTASES TREATMENT
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2023. pp. 85
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Leber Bettina
- Rosenkranz Alexander
- Stiegler Philipp
- Altmetrics:
- Abstract:
- Around 15-25% of patients, newly diagnosed with colorectal cancer (CRC), already have metastatic disease and it is considered to be the major cause of death. The most common site for CRC metastasis is the liver (CRCLM). Surgical CRCLM removal, is considered to be the only curative option, but only around 20% of all patients are candidates for radical treatment at the time of diagnosis. For the other 80% of these patients, the main treatment option remains systemic chemotherapy (CTx). During the administration of CTx, numerous adverse effects can occur, which can cause life-threatening conditions. Furthermore, CRCLM eventually tends to develop resistance to CTx. In such cases, novel treatment additives are necessary to better control the disease and improve patient quality of life. The increased research interest in gut health and probiotics lead to promising findings for the treatment of various clinical conditions, including data on probiotics as a tool in CRC management. Currently, there are no studies directly examining probiotic effects on CRCLM. This dissertation thesis aimed to assess the role of probiotic supplementation in CRCLM treatment. Six-week-old male Wistar rats received either a multispecies probiotic (1.2 × 109 CFU/day) or a placebo mixture. On day 14 of the experiment, rat CRC cells (CC531) were implanted under the liver capsule. On the 28th experiment day rats received FOLFOX CTx. Change in tumor volume was measured by performing micro-CT scanning. Stool samples were collected for further microbiome analysis. Additionally, immunohistochemical stainings of gut, liver and heart samples were performed. Tumor volume analysis revealed that probiotic supplementation reduces tumor growth. No synergistic effects between probiotic supplementation and FOLFOX CTx was observed. Diminished tumor growth was achieved by suppressing angiogenesis, as tumor microvascular density was significantly lower in rats receiving probiotic supplementation. Additionally, probiotics alleviated the severity and length of CTx-induced diarrhea. Furthermore, probiotics significantly reduced FOLFOX induced weight and blood albumin loss. No CTx-induced liver and heart injuries were noted upon closer blood and tissue sample inspection. In conclusion, our study was able to demonstrate that multispecies probiotic supplementation significantly inhibits CRCLM angiogenesis and decreases tumor growth. Additionally, we showed that probiotic supplementation could alleviate FOLFOX-induced intestinal mucositis symptoms and preserve both weight and blood albumin levels.