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  • Fecal microbiome and metabolome differ in healthy and food-allergic twins. The Journal of clinical investigation Bao, R., Hesser, L. A., He, Z., Zhou, X., Nadeau, K. C., Nagler, C. R. 2021; 131 (2)


    BACKGROUNDThere 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.METHODSTo 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.RESULTSA 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.CONCLUSIONTwin 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 REGISTRATIONParticipants in this study were recruited as part of an observational study ( NCT01613885) at multiple sites from 2014 to 2018.FUNDINGThis 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.

    View details for DOI 10.1172/JCI141935

    View details for PubMedID 33463536

  • Identification of cross-reactive allergens in cashew- and pistachio-allergic children during oral immunotherapy. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology He, Z., Dongre, P., Lyu, S., Manohar, M., Chinthrajah, R. S., Galli, S. J., DeKruyff, R. H., Nadeau, K. C., Andorf, S. 2020


    It has been estimated that around 8% of the children in the U.S. suffer from food allergy and of those, 40% are allergic to multiple foods. Among tree nuts, allergies to pistachios are common in those with cashew nut allergy and multiple homologous allergenic components are shared between the two nuts. Three major allergens from cashew (Ana o 1 at 50 kDa, Ana o 2 major band at 33 kDa and minor band at 53 kDa, and Ana o 3 at 10 kDa) and five major allergens from pistachio (Pis v 1 at 7 kDa, Pis v 2 at 32 kDa, Pis v 3 at 50 kDa, Pis v 4 at 23 kDa, and Pis v 5 at 36 kDa) have been identified. Of those, Ana o 1 and Pis v 3, Ana o 2 and Pis v 2, Ana o 2 and Pis v 5, Ana o 3 and Pis v 1 have been recognized as homologues based on their sequence similarity and cross reactivity to IgE from the patients.

    View details for DOI 10.1111/pai.13258

    View details for PubMedID 32323379

  • Increased diversity of gut microbiota during active oral immunotherapy in peanut allergic adults. Allergy He, Z., Vadali, V. G., Szabady, R. L., Zhang, W., Norman, J. M., Roberts, B., Tibshirani, R., Desai, M., Chinthrajah, R. S., Galli, S. J., Andorf, S., Nadeau, K. C. 2020

    View details for DOI 10.1111/all.14540

    View details for PubMedID 32750160

  • Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging JOURNAL OF IMMUNOLOGY He, Z., Allers, C., Sugimoto, C., Ahmed, N., Fujioka, H., Kim, W., Didier, E. S., Kuroda, M. J. 2018; 200 (12): 4059–67


    Neutrophils, basophils, and monocytes are continuously produced in bone marrow via myelopoiesis, circulate in blood, and are eventually removed from circulation to maintain homeostasis. To quantitate the kinetics of myeloid cell movement during homeostasis, we applied 5-bromo-2'-deoxyuridine pulse labeling in healthy rhesus macaques (Macaca mulatta) followed by hematology and flow cytometry analyses. Results were applied to a mathematical model, and the blood circulating half-life and daily production, respectively, of each cell type from macaques aged 5-10 y old were calculated for neutrophils (1.63 ± 0.16 d, 1.42 × 109 cells/l/d), basophils (1.78 ± 0.30 d, 5.89 × 106 cells/l/d), and CD14+CD16- classical monocytes (1.01 ± 0.15 d, 3.09 × 108 cells/l/d). Classical monocytes were released into the blood circulation as early as 1 d after dividing, whereas neutrophils remained in bone marrow 4-5 d before being released. Among granulocytes, neutrophils and basophils exhibited distinct kinetics in bone marrow maturation time and blood circulation. With increasing chronological age, there was a significant decrease in daily production of neutrophils and basophils, but the half-life of these granulocytes remained unchanged between 3 and 19 y of age. In contrast, daily production of classical monocytes remained stable through 19 y of age but exhibited a significant decline in half-life. These results demonstrated relatively short half-lives and continuous replenishment of neutrophils, basophils, and classical monocytes during homeostasis in adult rhesus macaques with compensations observed during increasing chronological age.

    View details for DOI 10.4049/jimmunol.1800207

    View details for Web of Science ID 000442386300020

    View details for PubMedID 29728510

    View details for PubMedCentralID PMC6263173