Fecal microbiome and metabolome differ in healthy and food-allergic twins
Riyue Bao, … , Kari C. Nadeau, Cathryn R. Nagler
Riyue Bao, … , Kari C. Nadeau, Cathryn R. Nagler
Published January 19, 2021
Citation Information: J Clin Invest. 2021;131(2):e141935. https://doi.org/10.1172/JCI141935.
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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 6

Distinct metabolic pathways are enriched in healthy and allergic twins.

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Distinct metabolic pathways are enriched in healthy and allergic twins. ...
(A) Metabolites more abundant in the healthy group (from Figure 5A) or in the allergic group (from Figure 5B) were enriched in different subpathways shown. Relative enrichment fold change is shown on the x axis, and the name of subpathway is shown on the y axis. P value and FDR-adjusted P value of each subpathway enrichment are shown next to each horizontal bar. (B and C) Representative examples of metabolites in the enriched subpathways in the healthy or allergic group. (B) The linoleoyl-linolenoyl-glycerol (18:2/18:3) [1]* (subpathway: Diacylglycerol) was higher in healthy (n = 13) compared with allergic (n = 23) twin members. (C) The secoisolariciresinol (subpathway: Food Component/Plant) was higher in allergic twin pairs (n = 23) compared with healthy twin pairs (n = 13). Supplemental Figure 10 shows the result of discordant twin pairs only that correspond to metabolites shown in B and C. In B and C, units shown on the y axis represent the normalized raw area counts of UPLC-MS/MS peaks, rescaled to set the median equal to 1.00 for each biochemical (see Methods). Each dot denotes 1 sample. The bounds of the boxes represent the 25th and 75th percentiles, the horizontal center lines indicate the medians, and the whiskers extend to data points within a maximum of 1.5 times the IQR. In A, the hypergeometric test was used to compute the P values of relative enrichment of metabolite subpathways and filtered by FDR-adjusted P < 0.10. Pathways consisting of at least 2 significant metabolites were included in the statistical test. After BH-FDR multiple-testing correction DAG remained as the most significantly enriched subpathway in metabolites more abundant in healthy twins (FDR-adjusted P < 0.00001). In B and C, 2-tailed Welch’s 2-sample t test was used on all samples.