Two-generation mouse model reflecting human microbiota

We used a two-generation HMA mouse model in which dams were colonized with human feces from three groups of infants (n = 19, samples collected during the first 8 weeks of life). In two of the groups, all infants had a strong hereditary risk for allergic disease (n = 12), but only 6 of them developed allergy before 2 years of age. In the third group, which was used as a control, none of the infants had allergic heredity or developed allergy (n = 7). Microbiota trajectories were followed from inoculation to mouse offspring, and metabolic profiles were monitored in several intestinal organs as well as in the serum of the murine offspring.

Microbiota composition and metabolome patterns persist across generations

The human microbiota adapted to the murine host but still presented distinct compositional features, reflecting the original inoculated samples. These microbial differences were mirrored in the mouse offspring metabolome, with group-associated patterns in sphingolipids, acylcarnitines and tryptophan metabolites. Furthermore, the metabolic profiles of the mouse offspring aligned with those observed in fecal water preparations from the corresponding human infant fecal samples.

Microbiota and metabolism reflect allergy risk groups

Our findings highlight the significant impact of early-life microbiota on the host metabolome and show that our two-generation HMA model is suitable for studying microbiota‒metabolome relationships relevant to humans. The differences in microbiota‒metabolome relations between individuals who develop or do not develop allergic disease suggest that an allergic predisposition might be more multifaceted than previously believed.

Illustration: Ymke De Jong