Gut microbiome immaturity and childhood acute lymphoblastic leukaemia

Abstract

Acute lymphoblastic leukaemia (ALL) is the most common cancer of childhood. Here, we map emerging evidence suggesting that children with ALL at the time of diagnosis may have a delayed maturation of the gut microbiome compared with healthy children. This finding may be associated with early-life epidemiological factors previously identified as risk indicators for childhood ALL, including caesarean section birth, diminished breast feeding and paucity of social contacts. The consistently observed deficiency in short-chain fatty-acid-producing bacterial taxa in children with ALL has the potential to promote dysregulated immune responses and to, ultimately, increase the risk of transformation of preleukaemic clones in response to common infectious triggers. These data endorse the concept that a microbiome deficit in early life may contribute to the development of the major subtypes of childhood ALL and encourage the notion of risk-reducing microbiome-targeted intervention in the future.

Exclusive Breastfeeding Duration and Risk of Childhood Cancers

“…In this register-based cohort study, we found that longer duration of exclusive breastfeeding (ie, for a period of at least 3 months) was associated with reduced risk of childhood BCP-ALL. This finding is consistent with emerging investigations implicating early gut microbiome maturation in childhood BCP-ALL pathogenesis . To inform future preemptive interventions, additional studies should investigate the biologic mechanisms underlying the observed association.…”

“…This finding is consistent with emerging investigations implicating early gut microbiome maturation in childhood BCP-ALL pathogenesis. 16,17,30…”

“…The association between breastfeeding and childhood BCP-ALL risk, if determined to be causal, could be mediated by preventing this immunologic dysregulation . Specifically, breastfeeding provides passive protection against infections and inflammation through antibody transmission and anti-inflammatory properties and also directly influences the shaping of the infant’s gut microbiome, important for immune system maturation …”

“…The role of gut microbiome maturation in childhood ALL pathogenesis and the potential for gut microbiome–targeted preemptive interventions has recently gained increasing attention . Several studies have shown that children with ALL have alterations of their gut microbiome at diagnosis compared with healthy peers .…”

“…Moreover, in these predisposed mice, leukemia development could be triggered by the destruction of the gut microbiome with antibiotics, even in the absence of infectious stimuli . It has therefore been suggested that suboptimal enrichment and delayed maturation of the gut microbiome may increase BCP-ALL risk in children born with preleukemic cells …”