Abstract
From immunology to neuroscience, interactions between the microbiome and host are increasingly appreciated as potent drivers of health and disease. Epidemiological studies previously identified compelling correlations between perinatal microbiome insults and neurobehavioral outcomes, the mechanistic details of which are just beginning to take shape thanks to germ-free and antibiotics-based animal models. This review summarizes parallel developments from clinical and preclinical research that suggest neuroactive roles for gut bacteria and their metabolites. We also examine the nascent field of microbiome-microglia crosstalk research, which includes pharmacological and genetic strategies to inform functional capabilities of microglia in response to microbial programming. Finally, we address an emerging hypothesis behind neurodevelopmental disorders, which implicates microbiome dysbiosis in the atypical programming of neuroimmune cells, namely microglia.
Highlights
The various microbial ecosystems (“microbiota”) and their component genes (“microbiomes”) existing on and within the host body are increasingly recognized as significant contributors to a functional host immune system
The latter interaction is especially critical in early development, as the colonization of the infant gut with an initial inoculum of maternal microbiota primes the neonatal peripheral immune system [4, 5]
Developmental shifts in gut microbial composition align with milestones in brain development, such as neuronal migration and proliferation, myelination, and synaptic pruning (Figure 2). These developmental correlations do not necessarily indicate a causal relationship, strong evidence from experimental models using germ-free (GF) and antibiotictreated rodents showed that the complete absence or severe reduction of gut microbiota, respectively, resulted in altered brain chemistry, transcriptional changes, and atypical behaviors compared to controls [18, 26, 27]
Summary
The various microbial ecosystems (“microbiota”) and their component genes (“microbiomes”) existing on and within the host body are increasingly recognized as significant contributors to a functional host immune system. In the gut, where microbial density is the highest, some of these functions include forming a physical barrier against infection by pathogenic microbes, acting as a bioreactor for digestion and nutrient absorption, and sensitizing the host immune system [3]. The latter interaction is especially critical in early development, as the colonization of the infant gut with an initial inoculum of maternal microbiota primes the neonatal peripheral immune system [4, 5]
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