Hypotheses regarding the current rise in food allergies in Westernized countries tend to focus on the effect of an altered gut microbiome due to lifestyle changes. Among them, Westernized dietary patterns (but also antibiotic misuse and higher rates of Caesarean birth), have been the most closely studied factors in terms of their possible adverse effect on the gut microbiome, especially during early life. However, the way immune cells in the intestinal mucosa distinguish innocuous dietary antigens and gut bacteria from pathogenic microbes and mount an appropriate response to each is poorly understood.
New research, led by Dr. Cathryn Nagler from the Department of Pathology at The University of Chicago (Illinois, USA), has found that gut commensal bacteria may dictate the development of an allergic response against cow’s milk by modulating genes from ileal intestinal epithelial cells.
Based on previous findings showing that infants with cow’s milk allergy (CMA) have a different fecal microbiota when compared with healthy infants, the researchers sought to explore the causal role of gut microbiota in protecting against CMA in a gnotobiotic mouse model.
Germ-free mice were colonized with feces from extensively hydrolyzed casein formula-fed CMA or formula-fed healthy infants. Mice transferred with bacteria from healthy infants were protected against anaphylactic responses to the cow’s milk allergen beta-lactoglobulin (BLG), reported by a stable core body temperature over time and decreased serum BLG-specific IgE and BLG-specific IgG1 levels when compared with CMA-colonized mice. The formula containing cow’s milk was not responsible for protecting against anaphylaxis in the healthy-colonized mice, as mice colonized with feces from breast-fed CMA infants were not protected from an anaphylactic response to the BLG challenge.
The gut microbiome composition was different between CMA and healthy infant donors (34 operational taxonomic units—OTUs—were more abundant in healthy donors and 24 OTUs were more abundant in CMA donors) and also allowed for the separating of healthy- and CMA-colonized mice. The analysis of enriched taxa in healthy-colonized mice or CMA-colonized mice revealed that bacteria from the Lachnospiraceae family were enriched in the healthy-colonized mice, in agreement with previous data.
Considering commensal bacteria residing in the ileum are relevant modulators of mucosal immune homeostasis, thanks to their interaction with intestinal epithelial cells, researchers analyzed correlations between ileal bacteria and ileal differentially expressed genes. Healthy-colonized mice showed an upregulated gene profile (e.g. genes encoding for gluconeogenic enzymes) that was completely different from those in CMA-colonized mice. These data, therefore, show that a unique profile of genes in ileal intestinal epithelial cells help distinguish healthy- and CMA-colonized mice, suggesting that ileal bacteria may play a role in modulating the allergic response to cow’s milk.
Furthermore, nine OTUs were found to be correlated with genes upregulated in the ileum of healthy- or CMA-colonized mice. In healthy-colonized mice, three out of five of the protective OTUs associated with upregulated ileal genes belonged to the Lachnospiraceae family and Anaerostipes caccae was the most enriched species. The subsequent colonization of germ-free mice with A. caccae confirmed its protective role against an anaphylactic response to BLG challenge.
Overall, these findings show the gut microbiota’s involvement in protecting the host against food allergies. Together with previous findings showing the role of combined probiotic and peanut oral immunotherapy against the allergic immune response to peanuts, this new research supports the notion that therapies aimed at modulating the gut microbiota are worth exploring. However, a close look at mechanisms underlying interactions between host cells and bacterial communities is needed before drawing up advice on manipulating intestinal bacteria for food allergy management.
Feehley T, Plunkett CH, Bao R, et al. Healthy infants harbor intestinal bacteria that protect against food allergy. Nat Med. 2019. doi: 10.1038/s41591-018-0324-z.