Maternal Lactobacillus johnsonii Supplementation Is Associated with Altered Offspring Cecal Microbiome and Reduced Cockroach Allergen-Induced Airway Responses in Mice

Background: Early-life microbial exposures shape immune maturation and can influence later susceptibility to allergic airway disease. While probiotics can modulate host immunity, determining whether maternal probiotic supplementation alone promotes changes in offspring microbiomes and the immune functions that reduce allergic disease remains incompletely defined. Methods: Female mice were gavaged with Lactobacillus johnsonii (Lj) daily for 7 days prior to mating, and then twice weekly until delivery. Offspring were sensitized and challenged with cockroach allergen (CRA), beginning at 5 weeks of age, for 3 weeks to initiate asthmatic-type responses. Airway physiology (methacholine-induced airway hyperreactivity; AHR), lung-mucus-related gene expression (Muc5ac, Gob5), and lymph node restimulation responses were assessed. Results: Offspring from Lj-supplemented dams exhibited reduced AHR and decreased induction of Muc5ac and Gob5 following the final CRA challenge, accompanied by diminished Th cell cytokine production upon lymph node restimulation. Maternal Lj supplementation produced a significant shift in offspring cecal microbiome structure at 5 weeks, including altered phylum-level composition and a discrete set of significantly changed OTUs, including Akkermansia. PICRUSt2 analyses predicted coordinated differences in microbial metabolic potential across multiple pathways, consistent with functional reprogramming of the gut microbiome. Bone marrow dendritic cells (BMDC) derived from adult offspring of Lj-supplemented dams showed attenuated inflammatory programming after RSV or TLR7 stimulation, with reduced expression of innate immune cytokines compared to PBS-supplemented dams. Conclusions: The relatively long-term effects were associated with reduced allergic airway disease severity, supporting maternal probiotic supplementation as a potential strategy to lower offsprings’ risk of allergic airway pathology.