General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz, Austria.
Faculty of Medicine, Vilnius University, M. K. Ciurlionio str. 21, 03101 Vilnius, Lithuania.
Nutrients. 2023 Feb 23;15(5):1117. doi: 10.3390/nu15051117.
The use of chemotherapeutic agents is of paramount importance when treating colorectal cancer (CRC). Unfortunately, one of the most frequent chemotherapy (CTx) side effects is intestinal mucositis (IM), which may present with several clinical symptoms such as nausea, bloating, vomiting, pain, and diarrhea and even can result in life-threatening complications. There is a focused scientific effort towards developing new therapies to prevent and treat IM. The aim of this study was to assess the outcomes of probiotic supplementation on CTx-induced IM in a CRC liver metastasis rat model. Six-week-old male Wistar rats received either a multispecies probiotic or placebo mixture. On the 28th experiment day, rats received FOLFOX CTx, and afterwards, the severity of diarrhea was evaluated twice daily. Stool samples were collected for further microbiome analysis. Additionally, immunohistochemical stainings of ileum and colon samples with were performed with MPO, Ki67, and Caspase-3 antibodies. Probiotic supplementation alleviates the severity and length of CTx-induced diarrhea. Additionally, probiotics significantly reduced FOLFOX-induced weight and blood albumin loss. Furthermore, probiotic supplementation mitigated CTx-induced histological changes in the gut and promoted intestinal cell regeneration. This study shows that multispecies probiotic supplementation attenuates FOLFOX-induced IM symptoms by inhibiting apoptosis and promoting intestinal cell proliferation.
在治疗结直肠癌(CRC)时,化疗药物的使用至关重要。不幸的是,最常见的化疗(CTx)副作用之一是肠黏膜炎(IM),其可能出现多种临床症状,如恶心、腹胀、呕吐、疼痛和腹泻,甚至可能导致危及生命的并发症。目前,科学界正在集中精力开发新的疗法来预防和治疗 IM。本研究旨在评估益生菌补充剂对 CRC 肝转移大鼠模型中 CTx 诱导的 IM 的治疗效果。六周龄雄性 Wistar 大鼠接受多菌种益生菌或安慰剂混合物处理。在第 28 天实验日,大鼠接受 FOLFOX CTx,之后每天评估两次腹泻严重程度。收集粪便样本进行进一步的微生物组分析。此外,还对回肠和结肠样本进行 MPO、Ki67 和 Caspase-3 抗体的免疫组织化学染色。益生菌补充剂可减轻 CTx 诱导的腹泻的严重程度和持续时间。此外,益生菌显著降低了 FOLFOX 引起的体重和血液白蛋白损失。此外,益生菌补充剂减轻了 CTx 诱导的肠道组织学变化,并促进了肠道细胞再生。本研究表明,多菌种益生菌补充剂通过抑制细胞凋亡和促进肠道细胞增殖来减轻 FOLFOX 诱导的 IM 症状。