Alcohol consumption during pregnancy differentially affects the fecal microbiota of dams and offspring

Abstract

Microbiota imbalances are linked to inflammation and disease, as well as neurodevelopmental conditions where they may contribute to behavioral, physiological, and central nervous system dysfunction. By contrast, the role of the microbiota in Fetal Alcohol Spectrum Disorder (FASD), the group of neurodevelopmental conditions that can occur following prenatal alcohol exposure (PAE), has not received similar attention. Here we utilized a rodent model of alcohol consumption during pregnancy to characterize the impact of alcohol on the microbiota of dam-offspring dyads. Overall, bacterial diversity decreased in alcohol-consuming dams and community composition differed from that of controls in alcohol-consuming dams and their offspring. Bacterial taxa and predicted biochemical pathway composition were also altered with alcohol consumption/exposure; however, there was minimal overlap between the changes in dams and offspring. These findings illuminate the potential importance of the microbiota in the pathophysiology of FASD and support investigation into novel microbiota-based interventions.

Figure 1

Bacterial richness and evenness (α-diversity). Boxplots displaying the Shannon index (α-diversity) for dams (A) and offspring (B). *p < 0.05; A alcohol, PAE prenatal alcohol exposure, C control. A dams: n = 20; C dams = 24; PAE offspring: n = 22; C offspring: n = 25.

Figure 2

Bacterial community structure (β-diversity). Non-metric multidimensional scaling (NMDS) plots of Bray–Curtis dissimilarity with ellipsoids representing 95% confidence intervals for dams (A) and offspring (B). ***p < 0.001; A alcohol, PAE prenatal alcohol exposure, C control. A dams: n = 20; C dams = 24; PAE offspring: n = 23; C offspring: n = 26.

Figure 3

Relative abundance of bacterial taxa. Relative abundance plots of the 15 most abundant bacterial genera for dams (A) and offspring (B). All other genera shown as other (grey). PAE prenatal alcohol exposure. A dams: n = 20; C dams = 24; PAE offspring: n = 23; C offspring: n = 26.

Figure 4

Impact of alcohol consumption and PAE on bacterial clades. Linear discriminant analysis of effect size (LEfSe), with the cladogram representing the complete taxonomy (from phylum to species). Purple shading indicates a taxon that is enriched in alcohol consuming dams (A) or PAE offspring (B), whereas orange shading indicates a taxon that is decreased in alcohol consuming dams (A) or PAE offspring (B). Yellow circles indicate a taxon that does not differ in relative abundance between treatments. A alcohol, PAE prenatal alcohol exposure, C control, A dams: n = 20; C dams = 24; PAE offspring: n = 23; C offspring: n = 26.

Figure 5

Comparison of the overlap in shared ASVs between dyads. The percentage of ASVs that were shared between dam and offspring dyads, by treatment group. ***p < 0.001. A alcohol, PAE prenatal alcohol exposure, C control, Control dam—control offspring dyads: n = 22; Alcohol-consuming dam—PAE offspring: n = 17.

Figure 6

Predicted metabolic pathway composition (β-diversity). Non-metric multidimensional scaling (NMDS) plots of Bray–Curtis dissimilarity in two dimensions with ellipsoids representing 95% confidence intervals for dams (A) and offspring (B). *p < 0.05; ***p < 0.001; A alcohol, PAE prenatal alcohol exposure, C control; A dams: n = 20; C dams = 24; PAE offspring: n = 23; C offspring: n = 26.

Figure 7

Differential abundance between treatments in predicted metabolic pathways. DESeq2 identifying predicted pathways that were significantly different with alcohol consumption (A) or exposure (B). Orange dots indicate decreases and purple dots indicate increases in alcohol consuming dams compared to controls (A) or PAE offspring compared to controls (B), respectively, with the size of the dot being proportional to the log2fold change in differential expression. Blue (controls) and red (alcohol consuming or PAE) dots represent the relative abundance of each pathway, for animals in which it was present. A and PAE samples were ordered based on maternal average alcohol consumption from GD7–14 (highest on the left to lowest on the right). A alcohol, PAE prenatal alcohol exposure, C control; A dams: n = 20, C dams = 24; PAE offspring: n = 23; C offspring: n = 26.