Abstract
Microbial colonization of the gut early in life is crucial for the development of the immune and nervous systems, as well as influencing metabolism and weight gain. While early life exposure to antibiotics can cause microbial dysbiosis, prebiotics are non-digestible substrates that selectively promote the growth of beneficial gut microbiota. Our objective was to examine the effects of dietary prebiotic administration on the consequences of maternal antibiotic intake on offspring body weight, behavior, and neuroimmune responses later in life. Sprague-Dawley rat dams were given low-dose penicillin (LDP), prebiotic fiber (10% oligofructose), or both, during the third week of pregnancy and throughout lactation. Anxiety-like behavior, weight gain, body composition, cecal microbiota composition, and microglial responses to lipopolysaccharide (LPS) were assessed in offspring. Male and female prebiotic offspring had lower body weight compared to antibiotic offspring. Maternal antibiotic exposure resulted in lasting effects on select offspring microbiota including a lower relative abundance of Streptococcus, Lactococcus, and Eubacterium at 10 weeks of age. Maternal antibiotic use impaired microglial response to LPS in the hypothalamus compared to control, and this phenotype was reversed with prebiotic. Prebiotic fiber warrants further investigation as an adjunct to antibiotic use during pregnancy.
Highlights
The establishment and development of the infant gut microbiota is a dynamic and complex process affected by perinatal conditions including maternal diet, mode of delivery, and antibiotic exposure [1,2]
We have previously found that prebiotic use in rats during pregnancy was associated with improved fertility and weight loss [23]; to our knowledge there are no studies that have examined whether prebiotics can improve microbiota-gut-brain axis function in conjunction with maternal antibiotic use
There was a significant effect of time (p = 0.0001), diet (p = 0.004), and time × diet (p = 0.0019) for body weight
Summary
The establishment and development of the infant gut microbiota is a dynamic and complex process affected by perinatal conditions including maternal diet, mode of delivery, and antibiotic exposure [1,2]. Transfer of microbiota to an infant via vertical transmission from the mother influences the development of the immune system, which in turn impacts brain development and function [3,4,5]. While the exact mechanisms by which microbial dysbiosis alters brain function remain to be elucidated, the pathways mediating these effects are part of the microbiota-gut-brain axis [7]. Microglia-mediated synaptic pruning has been shown to be altered following antibiotic exposure in mice, leading to deficits in fear extinction learning, which could only be reversed by selective re-establishment of the microbiota before weaning [9]. Supplementation with the prebiotic fiber, oligofructose-enriched inulin, was shown to improve age-related impairment of microglia, as well as reduce anxiety-like behavior and improve learning in young adult mice [10]
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