The interplay between the microbiota and host in health and disease is being extensively studied and the field is expanding exponentially. The microbiota is in symbiosis with its host and, especially during early life, actively influences the development of the host immune system. Disturbances of the gut microbiota during this window of opportunity can alter the microbial metabolism to an extent that it affects the host development for years thereafter. Dysbiosis or shifts in gut microbial composition have been shown to correlate with childhood allergy and asthma development. Together, these observations suggest that the microbiota is one of the driving forces for immune development and long-term memory.

In Paper I, we showed that early-life immune and gut microbiota signatures are associated with allergic asthma in young adulthood. By only selecting individuals who were genetically prone to become allergic, we could limit genetic variability and study the association of the early-life microbiota with young adulthood allergic asthma. Microbial composition development during the first 2 years of life differed between individuals who had developed allergic asthma in young adulthood compared to those who did not. Additionally, at age 2, we observed different immunological patterns in both dendritic cells and in peripheral blood mononuclear cells (PBMCs) transcriptomic profiles, with increased RNA processing and reduced immune pathway activity. Interestingly, these differences were less pronounced at 20 years of age, once asthma had developed, pointing to early life as a critical period during which microbiota-immune interactions may influence later asthma risk.

In Paper II, we connected specific gut microbial compositions with murine metabolic profiles linking the microbes with the host phenotype. Allergy-associated microbiota (AAM) fecal water stimulation induced inflammatory immune responses in PBMCs, while non-allergy associated microbiota (non-AAM) fecal water stimulation induced regulatory pathways. After transplanting the human early-life allergy associated and non-allergy associated fecal matter into germ-free mice, different metabolic patterns were observed in the intestine and distant organs. Increased levels of long acylcarnitines and sphingolipids were associated with the AAM transplanted mice, while non-AAM mice had higher levels of tryptophan and its derivatives. Our results suggest that the metabolites produced by non-AAM have a regulating, anti-inflammatory effect both in vitro and in vivo, despite adaptions in the microbial composition due to change of host environment.

In Paper III, we focused on isolating the microbiota from any host factors by developing a cost-efficient anaerobic bioreactor for culturing of complex microbial communities derived from intestinal samples. We managed to preserve the majority of the original microbial diversity and were able to establish a stable community to test the influence of antibiotic treatment on the dynamics. The magnitude of the perturbation by the antibiotic treatment depended on the original composition.

In summary, this work provides a glimpse into different ways of studying the gut microbiota-host associations and dynamics in relation to allergy and asthma.