Abstract
This review focuses on the current evidence that maternal dietary and gut bacterial exposures during pregnancy influence the developing fetal immune system and subsequent offspring asthma. Part 1 addresses exposure to a farm environment, antibiotics, and prebiotic and probiotic supplementation that together indicate the importance of bacterial experience in immune programming and offspring asthma. Part 2 outlines proposed mechanisms to explain these associations including bacterial exposure of the fetoplacental unit; immunoglobulin-related transplacental transport of gut bacterial components; cytokine signaling producing fetomaternal immune alignment; and immune programming via metabolites produced by gut bacteria. Part 3 focuses on the interplay between diet, gut bacteria, and bacterial metabolites. Maternal diet influences fecal bacterial composition, with dietary microbiota-accessible carbohydrates (MACs) selecting short-chain fatty acid (SCFA)-producing bacteria. Current evidence from mouse models indicates an association between increased maternal dietary MACs, SCFA exposure during pregnancy, and reduced offspring asthma that is, at least in part, mediated by the induction of regulatory T lymphocytes in the fetal lung. Part 4 discusses considerations for future studies investigating maternal diet-by-microbiome determinants of offspring asthma including the challenge of measuring dietary MAC intake; limitations of the existing measures of the gut microbiome composition and metabolic activity; measures of SCFA exposure; and the complexities of childhood respiratory health assessment.
Highlights
The human microbiome and its host form a complex symbiosis, and the gut microbiome is the primary interface for this relationship, harboring the most diverse array of microorganisms found in the human body [1]
We identified a single prospective study that examined the relationship between maternal fecal bacteria and offspring asthma as its primary outcome
There is evidence that antenatal interaction between maternal diet, gut bacteria, bacterial metabolites, and the developing fetal immune system influence offspring asthma. These associations have been linked, providing evidence that dietary MACs select a gut bacterial composition that produces increased SCFAs. These SCFAs influence T lymphocytes in the developing fetal immune system to produce a tolerogenic state that is associated with reduced risk of offspring wheeze and asthma
Summary
The human microbiome and its host form a complex symbiosis, and the gut microbiome is the primary interface for this relationship, harboring the most diverse array of microorganisms found in the human body [1]. Short-chain fatty acids (SCFAs) are the major metabolite produced by the gut bacteria from MACs. There is compelling evidence from mouse models linking variations in maternal dietary intake of MACs, gut bacteria, and SCFA production in the development of offspring asthma. There is compelling evidence from mouse models linking variations in maternal dietary intake of MACs, gut bacteria, and SCFA production in the development of offspring asthma These findings are yet to be confirmed in human studies. The aims of this review are to assess the current evidence regarding the influence of maternal dietary MACs and gut bacterial exposures during pregnancy on the developing fetal immune system and subsequent offspring asthma and discuss the considerations for future studies in this emerging field
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