This study is one of the highest quality I've ever reviewed in Evidence eMended (now approaching its 6th anniversary). Paradoxically, it has no immediate value to clinicians. It's still worthy of attention from pediatric healthcare providers, however, so keep reading.
Source: Arrieta M-C, Stiemsma LT, Dinitriu, et al. Early infancy microbial and metabolic alterations affect risk of childhood asthma.Sci Transl Med. 2015;7(307):307ra152; doi:10.1126/scitranslmed.aab2271. See AAP Grand Rounds commentary by Dr. Daniel Lesser (subscription required).
PICO Question: Among healthy infants, do those at risk of developing asthma have altered gut microbiota?
Question type: Descriptive
Study design: Case-control
This study represents an enormous amount of work. Clearly the authors avoided the "least publishable unit" dictum that many academicians employ to pad their cv's. The research is really a 3-parter: 1) a nested case control study of 319 children who underwent gut microbiome analysis to determine associations with atopy and wheezing; 2) an animal study, using replacement therapy with bacteria identified in the first study, to look at effects on lung inflammation; and 3) a test-tube study looking at how these organisms might be affecting development of lung inflammation.
The children being tested were enrolled through the Canadian Healthy Infant Longitudinal Development (CHILD) Study, which has a goal to identify genetic and environmental causes of allergy and asthma. The nested case control study examined the intestinal microbiome of infants in 4 groups: controls without positive atopy testing or wheezing episodes by a year of age (n=74), children with atopy only (n=87), wheezing only (n=136), and both atopy and wheezing (n=22). If you're not too familiar with what is meant by microbiome, check out a review by the authors of this study, or the NIH Human Microbiome Project. The authors of this extensive study found an association between 3 month old children in the atopy plus wheeze group and decreased amounts of 4 bacteria in the intestinal microbiome studied at 3 months of age. This quartet of bacteria is labelled FLVR for Faecalibacterium, Lachnospira, Veillonella, and Rothia species.
Then, the authors went further to look into potential biologic plausibility of this association. They fed germ-free mice with either a fecal sample from one atopy/wheezing infant or with the same fecal sample supplemented with FLVR bacteria. Looking at the subsequent offspring of these adult mice, they found a high degree of inflammatory airway response in the offspring of mice who received just the fecal sample, compared to those who also received the FLVR supplementation. They concluded that FLVR could ameliorate mouse lung inflammation in this experimental model.
The third portion of the study tried to examine how this association might be explained functionally, looking at fecal biochemical parameters and a very complex (i.e. beyond my understanding, even with my infectious disease background) series of analyses to infer changes in intestinal metabolic pathways, aka the metabolome.
In combination, the second and third components of this study lend credence to the findings of the case-control study. In answer to the question posed in the title of this postin: no, we are a long way from developing a new type of probiotic to counter environmental cofactors in development of asthma. However, this study suggests further investigation of FLVR organisms and the intestinal microbiome might lead to a completely novel approach to asthma and allergy prevention for infants.
