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Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring

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Jan 20, 2025 version files 4.07 GB

Abstract

Despite explosive rise in allergies, little is known about early life gut microbiota effects on postnatal respiratory function. We hypothesized that Enterobacteriaceae-dominant gut microbiota from eczemic infants increases Type 2 inflammation and decreases lung function in transplanted mice, while Bacteroidaceae-dominant gut microbiota from non-eczemic infants is protective. FMT from eczemic infants “Infant A” and non-eczemic infants “Infant B” were successfully transplanted into germ-free C57BL/6 mice passing to offspring unchanged. Infant A and B, Adult C-human-derived (positive control), and mouse (negative control) microbiotas all in C57BL/6 mice were tested for effects on airway function in non-allergic (PBS) and allergic (HDM) conditions. Baseline lung mechanics in mice with human microbiotas (HUmicrobiota) were significantly impaired compared to mouse microbiota controls (MOmicrobiota) with or without HDM; Respiratory system resistance (Rrs) was increased (p< 0.05-p<0.01) and Respiratory system compliance (Crs) was decreased (p<0.05-p<0.01). HUmicrobiota mice showed statistically significant impairment compared to MOmicrobiota mice in lung parameters Rrs, Ers, Rn, and G at baseline, and at multiple Mch doses with baseline removed. Impairment manifested as increased small airway resistance and tissue resistance. HDM significantly elevated IL-4, eosinophils, lung inflammation and mucus cell metaplasia and decreased macrophages and lung function (p<0.05) in mice of all microbiotas, yet each HUmicrobiota produced distinct features. Infant B and Adult C mice had elevated basal levels of total IgE compared to MOmicrobiota and Infant A mice (p<0.05). In HUmicrobiota mice given HDM, only Adult C had elevated IL-5 and IL-13 (p<0.05), only Adult C and Infant B mice had elevated neutrophils (p<0.05) and only Infant A had elevated lymphocytes (p<0.01).