Reduced microbial diversity in adult survivors of childhood acute lymphoblastic leukemia and microbial associations with increased immune activation

• Published in: Microbiome 2017-03, Vol.5 (1), p.35-35, Article 35
• Main Authors: Chua, Ling Ling, Rajasuriar, Reena, Azanan, Mohamad Shafiq, Abdullah, Noor Kamila, Tang, Mei San, Lee, Soo Ching, Woo, Yin Ling, Lim, Yvonne Ai Lian, Ariffin, Hany, Loke, P'ng
• Format: Article
• Language: English
• Subjects: Actinobacteria; Actinobacteria - genetics; Actinobacteria - isolation & purification; Adolescent; Adult; Anal Canal - microbiology; Bacteria - genetics; Bacteria - isolation & purification; Biodiversity; Biomarkers; C-Reactive Protein - analysis; Cancer therapies; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chemotherapy; Childhood; Corynebacterium; Deoxyribonucleic acid; Diabetes; Diabetes Mellitus, Type 2 - etiology; Disease; DNA; Dysbiosis; Feces; Genetic testing; Healthy Volunteers; HLA-DR Antigens; Homeostasis; Humans; Immune response; Immune system; Inflammation; Interleukin-6 - immunology; Leukemia; Lymphocyte Activation - immunology; Lymphocytes T; Metabolism; Metabolites; Microbiota; Obesity - etiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - microbiology; Surveillance; Survivors; Thermal cycling; Transplants & implants; Young Adult
• ISSN: 2049-2618; 2049-2618
• 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.