Reduced microbial diversity in adult survivors of childhood acute lymphoblastic leukemia and microbial associations with increased immune activation.
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.
University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Ling Ling
LL
Chua
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. reena@um.edu.my.|Centre of Excellence for Research in AIDS (CERIA), University of Malaya, 50603, Kuala Lumpur, Malaysia. reena@um.edu.my.|The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia. reena@um.edu.my.
Reena
R
Rajasuriar
University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia.|Department of Pediatric, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Mohamad Shafiq
MS
Azanan
Centre of Excellence for Research in AIDS (CERIA), University of Malaya, 50603, Kuala Lumpur, Malaysia.
Noor Kamila
NK
Abdullah
Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY, 10016, USA.
Mei San
MS
Tang
Centre of Excellence for Research in AIDS (CERIA), University of Malaya, 50603, Kuala Lumpur, Malaysia.|Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Soo Ching
SC
Lee
University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia.|Centre of Excellence for Research in AIDS (CERIA), University of Malaya, 50603, Kuala Lumpur, Malaysia.|Department of Obstetrics and Gynecology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Yin Ling
YL
Woo
Centre of Excellence for Research in AIDS (CERIA), University of Malaya, 50603, Kuala Lumpur, Malaysia.|Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Yvonne Ai Lian
YA
Lim
University Malaya Cancer Research Institute, University of Malaya, 50603, Kuala Lumpur, Malaysia. hany@ummc.edu.my.|Department of Pediatric, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. hany@ummc.edu.my.
Hany
H
Ariffin
Departments of Microbiology and Medicine, New York University School of Medicine, New York, NY, 10016, USA. png.loke@nyumc.org.
P'ng
P
Loke
D039903:Actinobacteria / Q000235:genetics / Q000302:isolation & purification; D000293:Adolescent; D000328:Adult; D001003:Anal Canal / Q000382:microbiology; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D044822:Biodiversity; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D064806:Dysbiosis; D006684:HLA-DR Antigens; D064368:Healthy Volunteers; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D064307:Microbiota; D009765:Obesity / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D017741:Survivors; D055815:Young Adult
D015415:Biomarkers; D006684:HLA-DR Antigens; D015850:Interleukin-6; D002097:C-Reactive Protein
Acute lymphoblastic leukemia; Adult survivors of childhood cancer; Alpha diversity; Immune activation; Inflammation; Microbiome; Microbiota dysbiosis