Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2H5, Canada.
Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, T6G 1Z2, Canada.
BMC Med. 2023 May 11;21(1):178. doi: 10.1186/s12916-023-02751-8.
Early-stage breast cancer patients treated with chemotherapy risk the development of metabolic disease and weight gain, which can result in increased morbidity and reduced quality of life in survivorship. We aimed to analyze changes within the gastrointestinal microbiome of early-stage breast cancer patients treated with and without chemotherapy to investigate a potential relationship between dysbiosis, a systemic inflammatory response, and resultant anthropomorphic changes.
We undertook an a priori analysis of serially collected stool and plasma samples from 40 patients with early-stage breast cancer who underwent adjuvant endocrine therapy only, adjuvant chemotherapy only, or both. Gut microbiota were assessed by metagenomic comparison of stool samples following deep sequencing. Inflammatory biomarkers were evaluated by proteomic analysis of plasma and measurement of fecal calprotectin. Body composition was investigated by dual-energy X-ray absorptiometry to determine biomass indices.
As opposed to treatment with endocrine therapy only, chemotherapy resulted in statistically and clinically significant weight gain and an increase in the android to gynoid ratio of fat distribution. Patients treated with chemotherapy gained an average of 0.15% total mass per month, as opposed to a significantly different loss of 0.19% in those patients who received endocrine-only therapy. Concurrently, a twofold increase in fecal calprotectin occurred after chemotherapy that is indicative of interferon-dependent inflammation and evidence of colonic inflammation. These anthropomorphic and inflammatory changes occurred in concert with a chemotherapy-dependent effect on the gut microbiome as evidenced by a reduction in both the abundance and variety of microbial species.
We confirm the association of chemotherapy treatment with weight gain and potential deleterious anthropometric changes and suggest that alterations of bacterial flora may contribute to these phenomena through the induction of systemic inflammation. Consequently, the gut microbiome may be a future target for intervention in preventing chemotherapy-dependent anthropometric changes.
接受化疗的早期乳腺癌患者有发生代谢疾病和体重增加的风险，这会导致发病率增加和生存质量降低。我们旨在分析接受和未接受化疗的早期乳腺癌患者胃肠道微生物组的变化，以研究肠道菌群失调、全身炎症反应与由此导致的人体测量学变化之间的潜在关系。
我们对 40 例接受辅助内分泌治疗、辅助化疗或两者联合治疗的早期乳腺癌患者的连续采集的粪便和血浆样本进行了预先分析。通过对粪便样本进行深度测序比较，评估肠道微生物群。通过对血浆进行蛋白质组分析和粪便钙卫蛋白的测量来评估炎症生物标志物。通过双能 X 射线吸收法测定身体成分，以确定生物量指数。
与仅接受内分泌治疗相比，化疗导致体重出现统计学和临床意义上的显著增加，脂肪分布的男性型到女性型比例增加。接受化疗的患者平均每月增加 0.15%的总质量，而仅接受内分泌治疗的患者则明显减少 0.19%。同时，化疗后粪便钙卫蛋白增加了两倍，这表明存在干扰素依赖性炎症和结肠炎症的证据。这些人体测量学和炎症变化与化疗对肠道微生物组的影响一致，表现为微生物种类的丰度和多样性均减少。
我们证实了化疗治疗与体重增加和潜在有害的人体测量变化之间的关联，并表明细菌菌群的改变可能通过诱导全身炎症导致这些现象。因此，肠道微生物组可能是预防化疗相关人体测量变化的未来干预靶点。
