Fecal microbiome and metabolome differ in healthy and food-allergic twins
Riyue Bao, Lauren A. Hesser, Ziyuan He, Xiaoying Zhou, Kari C. Nadeau, Cathryn R. Nagler
Riyue Bao, Lauren A. Hesser, Ziyuan He, Xiaoying Zhou, Kari C. Nadeau, Cathryn R. Nagler
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Clinical Research and Public Health Immunology

Fecal microbiome and metabolome differ in healthy and food-allergic twins

Abstract

BACKGROUND There has been a striking generational increase in the prevalence of food allergies. We have proposed that this increase can be explained, in part, by alterations in the commensal microbiome.METHODS To identify bacterial signatures and metabolic pathways that may influence the expression of this disease, we collected fecal samples from a unique, well-controlled cohort of twins concordant or discordant for food allergy. Samples were analyzed by integrating 16S rRNA gene amplicon sequencing and liquid chromatography–tandem mass spectrometry metabolite profiling.RESULTS A bacterial signature of 64 operational taxonomic units (OTUs) distinguished healthy from allergic twins; the OTUs enriched in the healthy twins were largely taxa from the Clostridia class. We detected significant enrichment in distinct metabolite pathways in each group. The enrichment of diacylglycerol in healthy twins is of particular interest for its potential as a readily measurable fecal biomarker of health. In addition, an integrated microbial-metabolomic analysis identified a significant association between healthy twins and Phascolarctobacterium faecium and Ruminococcus bromii, suggesting new possibilities for the development of live microbiome-modulating biotherapeutics.CONCLUSION Twin pairs exhibited significant differences in their fecal microbiomes and metabolomes through adulthood, suggesting that the gut microbiota may play a protective role in patients with food allergies beyond the infant stage.TRIAL REGISTRATION Participants in this study were recruited as part of an observational study (ClinicalTrials.gov NCT01613885) at multiple sites from 2014 to 2018.FUNDING This work was supported by the Sunshine Charitable Foundation; the Moss Family Foundation; the National Institute of Allergy and Infectious Diseases (NIAID) (R56AI134923 and R01AI 140134); the Sean N. Parker Center for Allergy and Asthma Research; the National Heart, Lung, and Blood Institute (R01 HL 118612); the Orsak family; the Kepner family; and the Stanford Institute for Immunity, Transplant and Infection.

Authors

Riyue Bao, Lauren A. Hesser, Ziyuan He, Xiaoying Zhou, Kari C. Nadeau, Cathryn R. Nagler

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Figure 3

Healthy twins exhibit a fecal microbial profile distinct from allergic siblings.

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Healthy twins exhibit a fecal microbial profile distinct from allergic s...
Relative abundance heatmap of the 64 OTUs identified to be differentially abundant between healthy (n = 12) and allergic (n = 22) twins. Of these 64 OTUs, 62 were more abundant in the healthy group (healthy-abundant OTUs), and 2 were more abundant in the allergic group (allergic-abundant OTU). OTU IDs are shown on the row in the format of “OTU_ID|Family,” and those annotated with the Clostridia class (Lachnospiraceae, Ruminococcaceae, unclassified Clostridiales) are highlighted in pink. Sample IDs are shown on the column, with annotation bars above the heatmap indicating concordant/discordant twin members, sex, and zygosity. A binary presence/absence heatmap of the 64 OTUs is shown in Supplemental Figure 3. Of 36 samples total in the twin cohort, 1 sample (S5077) failed sequencing and yielded 0 reads; therefore, the corresponding twin pair (no. 13) was excluded from 16S analysis. DS-FDR was used on all samples (P < 0.05) and 2-tailed Wilcoxon’s signed-rank test was used on discordant twin pairs (P < 0.10), respectively. Unadjusted P value thresholds were used to filter for OTUs of interest. After BH-FDR correction, no OTUs passed the FDR cutoff of 0.10 threshold, potentially due to small sample size.