关键词: Chemotherapy Intestinal microbiota Intestinal mucositis Probiotics Radiotherapy

Mesh : Humans Probiotics / administration & dosage Male Middle Aged Quality of Life Female Neoplasms / drug therapy Gastrointestinal Microbiome / physiology Aged COVID-19 Diarrhea / microbiology Cohort Studies Adult Feces / microbiology Mucositis Antineoplastic Agents / adverse effects

来  源:   DOI:10.1007/s10787-024-01503-1   PDF(Pubmed)

Abstract:
BACKGROUND: The efficacy of cancer treatments has links to the intestinal microbiome. Mucositis is a dose-limiting intestinal pro-inflammatory side effect of cancer treatments, that increases the risk of diarrhoea, mucositis, and in severe cases, febrile neutropenia.
METHODS: The effect of cancer treatments on Quality of Life (QoL) was assessed using the FACT C questionnaire that included patient wellbeing and gut adverse symptoms (e.g. diarrhoea). Participants rated faecal samples via the Bristol Stool Chart. In addition, bacterial DNA was extracted from faecal samples, sequenced, and taxonomically examined. The incidence / severity of neutropenia was assessed with white blood cell and neutrophil counts. Circulating SCFAs and plasma lipopolysaccharide (LPS) endotoxin levels were recorded and correlated to intestinal mucositis.
RESULTS: Improvement in bowel function, with reduction in constipation and or diarrhoea or absence of significant disturbance to bowel function was recorded in 85% of the participants. One participant developed febrile neutropenia and two developed bowel toxicity during the study, that was unrelated to the test formulation. No significant changes in microbiota alpha- and beta-diversity at the phylum and species levels respectively from baseline to end of study treatment was observed. None of the participants had raised plasma-endotoxin levels from baseline to the first and subsequent treatment cycles for their cancers. Probiotics in this cohort were deemed safe and tolerable. Significant improvement in emotional QoL scores (p = 0.015) was reported with increased number of chemotherapy cycles. In a related observational study of exceptional responders to chemotherapy, participants were found to have had a high intake of fruits, vegetables, and fibre possibly indicative of a more balanced intestinal microbiota.
CONCLUSIONS: A multi-strain probiotic formulation was safe and tolerated in this chronically ill cohort that were undergoing oncological treatment. The probiotic formulation alleviated diarrhoea, constipation and maintained stool consistency/frequency during the multiple treatments with chemotherapy and radiotherapy. Intestinal dysbiosis that is characterised by decreased microbial diversity and increased pro-inflammatory species was not observed. Probiotic supplementation may have helped reduce dysbiosis during cancer treatments. These improvements may have been critical with the observation that emotional wellbeing was significantly improved from baseline. Hence albeit that the study had limitations, the probiotic intervention provided adjunctive treatment support to the patients. What is of scientifically plausible interest is that probiotics have a long association historically with human hosts and as such ratify their inclusion offering a significant adjunctive therapeutic potential. Future studies warrant larger sample sizes, control groups and should limit recruitment to a largely homogenous group of patients.
摘要:
背景:癌症治疗的疗效与肠道微生物有关。粘膜炎是癌症治疗的剂量限制性肠道促炎副作用,这增加了腹泻的风险,粘膜炎,在严重的情况下,发热性中性粒细胞减少症.
方法:使用FACTC问卷评估癌症治疗对生活质量(QoL)的影响,问卷包括患者健康和肠道不良症状(如腹泻)。参与者通过布里斯托尔凳子图对粪便样本进行评级。此外,从粪便样本中提取细菌DNA,测序,并进行了分类学检查。用白细胞和中性粒细胞计数评估中性粒细胞减少症的发生率/严重程度。记录循环SCFA和血浆脂多糖(LPS)内毒素水平,并与肠粘膜炎相关。
结果:肠功能改善,在85%的参与者中,观察到便秘和/或腹泻减少或肠道功能无明显紊乱.在研究期间,一名参与者出现了发热性中性粒细胞减少症,两名参与者出现了肠毒性,这与测试配方无关。从基线到研究治疗结束,在门和物种水平上分别没有观察到微生物群α和β多样性的显着变化。没有参与者从基线到第一个和随后的癌症治疗周期的血浆内毒素水平升高。该队列中的益生菌被认为是安全和可耐受的。据报道,随着化疗周期数的增加,情绪QoL评分显着改善(p=0.015)。在一项关于化疗异常反应者的相关观察研究中,参与者被发现有大量的水果摄入量,蔬菜,和纤维可能表明肠道微生物群更加平衡。
结论:在接受肿瘤治疗的慢性病患者队列中,多菌株益生菌制剂是安全和耐受的。益生菌制剂缓解腹泻,在化疗和放疗的多种治疗期间,便秘和保持大便稠度/频率。未观察到以微生物多样性减少和促炎物种增加为特征的肠道菌群失调。益生菌补充剂可能有助于减少癌症治疗期间的生态失调。这些改善可能是至关重要的,因为观察到情绪健康从基线显着改善。因此,尽管这项研究有局限性,益生菌干预为患者提供了辅助治疗支持.科学上合理的兴趣是益生菌在历史上与人类宿主有着长期的联系,因此批准了它们的加入,从而提供了显着的辅助治疗潜力。未来的研究需要更大的样本量,对照组,应将招募限制在基本上同质的患者组中。
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