Healthy infants harbor intestinal bacteria that protect against food allergy

Abstract

There has been a striking generational increase in life-threatening food allergies in Westernized societies 1 , 2 One hypothesis to explain this rising prevalence is that 21 st century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early life alterations may be particularly detrimental. 3 , 4 To better understand how commensal bacteria regulate food allergy in humans we colonized germ free (GF) mice with feces from healthy or cow’s milk allergic (CMA) infants 5 . We show here that GF mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow’s milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transciptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a Clostridial species, Anaerostipes caccae , that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy.

Recent developments and highlights in food allergy

“…[97][98][99] Several recent studies have demonstrated that colonization of mice with fecal microbiota from food-allergic children does not protect the animals from food allergy, whereas colonization with microbiota from healthy children was protective. 100,101 While these studies and others suggest that multiple mechanisms might be involved, including but not limited to altered IgA reactivity, induction of regulatory cell subsets, or modification of epithelial metabolism, the consistent important finding is that the intestinal microbiome regulates allergic responses to dietary antigens and targeting the microbiome might be therapeutically effective in food allergy.…”

‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

“…Finally, antibiotic treatment of neonatal mice enhances the susceptibility towards food allergen sensitization and experimental psoriasis . Also in humans, exposure to microbial constituents protects children from asthma development and specific bacterial species have been identified and shown to protect from food allergy . Conversely, early‐life antibiotic treatment alters the metabolome through alteration of the microbiota and increases the risk of obesity and allergies .…”

Gut microbiota from infant with cow’s milk allergy promotes clinical and immune features of atopy in a murine model

“…No significant differences in fecal scores were recorded between HC-S and HC-NS, which may indicate a protective effect of healthy microbiota upon allergen exposure as we and others observed previously. 3,4 In addition, clinical scores (scratching/ puffiness/ loss of mobility) after oral challenge with β-lactoglobulin (BLG) were significantly higher in CMA-S group versus CMA-NS and HC-S groups ( Figure 2B). Minimal differences in mouse mast cell protease 1 (mMCP-1) and allergen-specific sensitization markers were observed between the two fecal transfers ( Figure 2C-E), which contrasted with the increases observed in total IgE levels and total IgG1/IgG2a ratio in CMA-S and CMA-NS groups compared with HC-S and HC-NS groups, respectively ( Figure 2F,G).…”