Early Infancy Microbial and Metabolic Alterations Affect Risk of Childhood Asthma

Marie-Claire Arrieta, Leah T. Stiemsma, Pedro A. Dimitriu, Lisa Thorson, Shannon Russell,Sophie Yurist-Doutsch, Boris Kuzeljevic, Matthew J. Gold, Heidi M. Britton, Diana L. Lefebvre,Padmaja Subbarao, Piush Mandhane, Allan Becker, Kelly M. McNagny, Malcolm R. Sears, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, Stuart E. Turvey and B. Brett Finlay

(from left to right) Dr. Brett Finlay, Dr. Marie-Claire Arrieta, Leah Stiemsma, and Dr. Stuart Turvey

(From left to right) Dr. Brett Finlay, Dr. Marie-Claire Arrieta, Leah Stiemsma, and Dr. Stuart Turvey

Asthma currently affects over 300 million people worldwide and is the most prevalent childhood disease. Research in mice suggests an early life critical window in which disturbances to the gut microbiota are most influential in shaping the immune system and potentially biasing it toward the development of hypersensitivities. In our recent publication in Science Translational Medicine, we translated some of these findings into humans. We selected 319 one-year-old children from the Canadian Healthy Infant Longitudinal Development (CHILD) Study for microbiome analysis and supported a link between early life gut microbial dysbiosis (dysbiosis before 3-months of age), characterized by reductions in four bacterial genera—Faecalibacterium, Lachnospira, Veillonella, and Rothia (FLVR)—and an increased risk to develop asthma. This reduction in FLVR was accompanied by a reduction in the fecal short chain fatty acid, acetate, and shifts in the production of microbial-derived metabolites in urine. Further, moving from correlation to causation, we showed that inoculation of germ free mice with FLVR ameliorated airway inflammation in their adult progeny, suggesting a protective role of these bacteria against lung inflammation. Ultimately, these results increase the potential for microbe-based therapeutics as a preventative measure against asthma and atopic disease development in children.