Early life antibiotic‐driven changes in microbiota enhance susceptibility to allergic asthma

Abstract

Allergic asthma rates have increased steadily in developed countries, arguing for an environmental aetiology. To assess the influence of gut microbiota on experimental murine allergic asthma, we treated neonatal mice with clinical doses of two widely used antibiotics—streptomycin and vancomycin—and evaluated resulting shifts in resident flora and subsequent susceptibility to allergic asthma. Streptomycin treatment had little effect on the microbiota and on disease, whereas vancomycin reduced microbial diversity, shifted the composition of the bacterial population and enhanced disease severity. Neither antibiotic had a significant effect when administered to adult mice. Consistent with the ‘hygiene hypothesis’, our data support a neonatal, microbiota‐driven, specific increase in susceptibility to experimental murine allergic asthma.

Commensal bacteria protect against food allergen sensitization

“…1E, no treatment, NT) were absent in fecal samples obtained from Abx-treated mice and were replaced instead by Lactobacillaceae (Fig. 1E), consistent with another recent report (13).…”

The Progress of Food Allergy Concept, Classifications and Diagnosis

“…[ [41][42] Administration of defined commensal microbiota, such as Clostridia species and Bactericides fragilis, or short-chain fatty acids (microbiota-derived products) to GF mice induced Treg cells [40,[43][44] and reduced allergic sensitization, [40] supporting the notion that intestinal commensal microbiota promote Treg cells and limit allergic responses to foods. Il4raF709 mice carrying a gain-of-function mutation in IL-4 receptor a-chain, which are susceptible to allergic sensitization and anaphylaxis, [45][46] exhibit an altered gut Microbiota signature from that seen in control mice.…”

“…While germ-free (GF) conditions are almost impossible in human studies, limiting the types of analysis that can be performed, a role for commensal microbiota in promoting oral tolerance has been clearly defined by using gnotobiotic mice, in which reconstitution of GF mice with well-characterized communities of microbiota or defined bacteria has been performed. Numbers of CD41Foxp31 Treg cells are reduced in antibiotic-treated mice or GF mice, [40][41] which exhibit a prides position toward allergic sensitization.…”

Reciprocity in Microbiome and Immune System Interactions and its Implications in Disease and Health

“…In an allergic disease mouse model, intestinal microbiota, particularly during early infancy, play a critical role in regulating immune responses to avoid atopy. In this respect, administration of antibiotics in neonatal mice changes the composition of the bacterial population and exacerbates experimental murine allergic asthma [57]. An inverse relation between Helicobacter pylori presence in human stomach and allergic asthma has been proposed [58].…”

“…A mixture of clostridia species induces IL-10 producing Tregs in the colonic lamina propria of germ free mice that is independent from MyD88 signaling pathway [1]. The effect of MyD88 pathway in microbiota-mediated modulation of immune response has been described by using MyD88 knockout mice [57]. To add another layer to the complexity of microbiomehost interactions, a deficiency in TLR or MyD88 signaling pathway in mice by itself could alter the composition of gut microbiota that secondarily affects immune system.…”