University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Microbiome. 2017 Mar 20;5(1):35. doi: 10.1186/s40168-017-0250-1.
Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) have health problems that persist or develop years after cessation of therapy. These late effects include chronic inflammation-related comorbidities such as obesity and type 2 diabetes, but the underlying cause is poorly understood.
We compared the anal microbiota composition of adult survivors of childhood ALL (N = 73) with healthy control subjects (N = 61). We identified an altered community with reduced microbial diversity in cancer survivors, who also exhibit signs of immune dysregulation including increased T cell activation and chronic inflammation. The bacterial community among cancer survivors was enriched for Actinobacteria (e.g. genus Corynebacterium) and depleted of Faecalibacterium, correlating with plasma concentrations of IL-6 and CRP and HLA-DR+CD4+ and HLA-DR+CD8+ T cells, which are established markers of inflammation and immune activation.
We demonstrated a relationship between microbial dysbiosis and immune dysregulation in adult ALL survivors. These observations suggest that interventions that could restore microbial diversity may ameliorate chronic inflammation and, consequently, development of late effects of childhood cancer survivors.
儿童癌症（如急性淋巴细胞白血病，ALL）的成年幸存者在治疗停止多年后仍存在或出现健康问题。这些晚期效应包括与慢性炎症相关的合并症，如肥胖症和 2 型糖尿病，但根本原因尚不清楚。
我们比较了 73 名 ALL 儿童成年幸存者和 61 名健康对照者的肛门微生物群组成。我们发现癌症幸存者的微生物多样性降低，群落发生改变，并且存在免疫失调的迹象，包括 T 细胞激活和慢性炎症增加。癌症幸存者的细菌群落富含放线菌（例如棒状杆菌属），而 Faecalibacterium 减少，与 IL-6 和 CRP 以及 HLA-DR+CD4+和 HLA-DR+CD8+T 细胞的血浆浓度相关，这些都是炎症和免疫激活的既定标志物。
我们证明了成人 ALL 幸存者中微生物失调与免疫失调之间存在关系。这些观察结果表明，恢复微生物多样性的干预措施可能会改善慢性炎症，从而改善儿童癌症幸存者的晚期效应。
