Can Microbes Protect from Asthma? Twitter summary from the 2019 WSAAI meeting

Donata Vercelli spoke on "Can Microbes Protect from Asthma? Studies with Amish & Hutterite Gut Microbiota".

Asthma & allergy are to a large extent environmental diseases that can be treated but not cured.

Erika von Mitius showed a "farm effect" in Alpine Europe, where exposure to cows, hay and unpasteurized milk lead to protection from allergies and asthma. Since then we have been asking and answering why this occurs with relations to genetics, specific farm exposures, and what other components of the farm environments are responsible for protection.

Recent NEJM article addressed two genetic similar populations from a specific region in Europe who settled in different areas of the US - the Amish and Hutterites. Their origins are only 800 km apart in Europe. But while they are very similar in origins (genetics), diet, religion, etc., their farming is very different. Amish non-mechanized single-family farms. Hutterites: large, industrial farming. So for asthma and allergic sensitization Amish are 3-4x lower than Hutterites. While there are differences in cell types (eosinophils, neutrophils, etc) there are no major difference in T regulatory cells.

Asthma protection requires innate immunity. Inflammation appears to generate a neutrophilic response as opposed to eosinophilic responses. This appears to depend on type of exposures and suggests that microbiome plays a strong relationship with risk of childhood asthma.

Gene expression patterns in PBLs of Amish and Hutterite children differ especially in innate immune pathways. Endotoxin much higher in Amish homes, a proxy for microbial load in these homes:

Dust collectors suggested inhalation of Amish, but not Hutterite, dust extract is sufficient to block allergen-induced airway hyperreactivity and eosinophilia in mice- important because even this dust was enough to create this phenotype. Found asthma protection in “Amish mice” requires innate immunity, most notably in MyD88-TRif.

Farm effect involved environmental microbiome:

This relationship of the risk of asthma and the gut microbiome happens very early:

Amish but not Hutterite fecal microbiota are sufficient to suppress allergen-induced AHR and OVA-specific IgE. Profiles of BAL eosinophilia in germ-free mice associated with Amish fecal microbiota showed regulatory eosinophils with regulatory transcription signatures (Prg3) in Amish mice (inflammatory eos in Hutterites).

What is happening between gut and environment? May be "pioneer taxa" are transferred from mother to infant, then the pioneers create a micro-environment for beneficial microbiota to come from the environment (dust) during the 1st year of life.

Dr. Lozupone talked on gut microbiome and how it affects health and inflammation:

Gut microbes affect your health by competitively excluding pathogens, metabolically transforming your diet and drugs, and modulating your immune system. Excellent summary!

Factors that influence microbiome: age, diet, location. Early microbe exposures influence allergy and asthma likely from epigenetic changes. Different approaches using microbiome therapeutics - transplant ecosystem, prebiotics, probiotics.

Dr. Laidlaw mentioned that they have good success with single day protocols.

Commensal micro-derived butyrate induces differentiation of colonic regulatory T Cells, driving the colon away from inflammation.

Age is associated with the most pronounced differences in the gut microbiome.

This is a Twitter summary from the 2019 WSAAI meeting. This summary was compiled from the tweets posted by Matthew Bowdish @MatthewBowdish and Ray Firszt @RayFirszt, who attended the 2019 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited by me.

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