Ziyuan He

Bio: Ziyuan He is an academic researcher from Stanford University. The author has contributed to research in topics: Food allergy & Asthma. The author has an hindex of 4, co-authored 12 publications receiving 37 citations. Previous affiliations of Ziyuan He include Tulane University.

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

Abstract: 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 (ClinicalTrials.gov 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.

Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19.

Abstract: Background It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. Methods All patients over 28 days old testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. Results 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS-CoV-2-positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non-allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. Conclusions Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared with non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post-infection.

Rapid Turnover and High Production Rate of Myeloid Cells in Adult Rhesus Macaques with Compensations during Aging

Abstract: 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.

Increased diversity of gut microbiota during active oral immunotherapy in peanut-allergic adults.

Abstract: R E FE R E N C E S 1. Carli G, Cecchi L, Stebbing J, Parronchi P, Farsi A. Is asthma protective against COVID-19? Allergy. 2021;76:866–936. 2. Mahdavinia M, Foster KJ, Jauregui E, et al. Asthma prolongs intubation in COVID-19. J Allergy Clin Immunol Pract. 2020;8(7):2388-2391. 3. Hooper MW, Nápoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA. 2020;323(24):2466-2467. 4. Noonan AS, Velasco-Mondragon HE, Wagner FA. Improving the health of African Americans in the USA: an overdue opportunity for social justice. Public Health Rev. 2016;37(1):1-20. 5. Nyenhuis SM, Krishnan JA, Berry A, et al. Race is associated with differences in airway inflammation in patients with asthma. J Allergy Clin Immunol. 2017;140(1):257-265.e211. 6. Lindsley AW, Schwartz JT, Rothenberg ME. Eosinophil responses during COVID-19 infections and coronavirus vaccination. J Allergy Clin Immunol. 2020;146(1):1-7.

A positive feedback loop reinforces the allergic immune response in human peanut allergy.

Abstract: Food allergies are a leading cause of anaphylaxis, and cellular mechanisms involving antigen presentation likely play key roles in their pathogenesis. However, little is known about the response of specific antigen-presenting cell (APC) subsets to food allergens in the setting of food allergies. Here, we show that in peanut-allergic humans, peanut allergen drives the differentiation of CD209+ monocyte-derived dendritic cells (DCs) and CD23+ (FcєRII) myeloid dendritic cells through the action of allergen-specific CD4+ T cells. CD209+ DCs act reciprocally on the same peanut-specific CD4+ T cell population to reinforce Th2 cytokine expression in a positive feedback loop, which may explain the persistence of established food allergy. In support of this novel model, we show clinically that the initiation of oral immunotherapy (OIT) in peanut-allergic patients is associated with a decrease in CD209+ DCs, suggesting that breaking the cycle of positive feedback is associated with therapeutic effect.

The level of monocyte turnover predicts disease progression in the macaque model of AIDS

Abstract: It is widely accepted that destruction of CD4(+) T cells and viral load are the primary markers for immunodeficiency in HIV-1-infected humans and in simian immunodeficiency virus (SIV)-infected macaques. However, monocyte/macrophages are also important targets of HIV/SIV infection and a critical link between innate and adaptive immunity. We therefore examined whether changes in cells of the monocyte/macrophage lineage could be linked to the pathogenesis of AIDS in the rhesus macaque model. Here, we show that massive turnover of peripheral monocytes associated with death of tissue macrophages correlates with AIDS progression in macaques. More importantly, the level of monocyte turnover was not linked to the CD4(+) T-cell count and was a better predictive marker for AIDS progression than was viral load or lymphocyte activation. Our results show the importance of monocyte/macrophages in the pathogenesis of AIDS and suggest the dynamic changes of the monocyte/macrophages as a new marker for AIDS progression.

Asthma and Coronavirus Disease 2019 Risk: a systematic review and meta-analysis.

Abstract: Background Individual case series and cohort studies have reported conflicting results on the vulnerability to and risk of mortality of people with asthma from COVID-19. Research Question Are people with asthma at a higher risk of being infected, hospitalised or of poorer clinical outcomes from COVID-19? Methods A systematic review and meta-analysis based on five main databases including the WHO COVID-19 database between December 1, 2019 to July 11, 2021 on studies with a control (non-asthma) group was conducted. Prevalence and risk ratios were pooled using Sidik-Jonkman random effects meta-analyses. Findings Fifty-one studies with an 8.08% (95% CI 6.87–9.30) pooled prevalence of people with asthma among COVID-19 positive cases. The risk ratios were 0.83 (95% CI 0.73–0.95, p=0.01) for acquiring COVID-19; 1.18 (95% CI 0.98–1.42, p=0.08) for hospitalisation; 1.21 (95% CI 0.97–1.51, p=0.09) for ICU admission; 1.06 (95% CI 0.82–1.36, p=0.65) for ventilator use and 0.94 (95% CI 0.76–1.17; p=0.58) for mortality for people with asthma. Subgroup analyses by continent revealed a significant difference in risk of acquiring COVID-19, ICU admission, ventilator use and death between the continents. Interpretation The risk of being infected with SARS-CoV-2 was reduced compared to the non-asthma group. No statistically significant differences in hospitalisation, ICU admission and ventilator use were found between groups. Subgroup analyses showed significant differences in outcomes from COVID-19 between America, Europe and Asia. Additional studies are required to confirm this risk profile, particularly in Africa and South America where few studies originate.

Integration, exploration, and analysis of high-dimensional single-cell cytometry data using Spectre.

Abstract: As the size and complexity of high-dimensional (HD) cytometry data continue to expand, comprehensive, scalable, and methodical computational analysis approaches are essential. Yet, contemporary clustering and dimensionality reduction tools alone are insufficient to analyze or reproduce analyses across large numbers of samples, batches, or experiments. Moreover, approaches that allow for the integration of data across batches or experiments are not well incorporated into computational toolkits to allow for streamlined workflows. Here we present Spectre, an R package that enables comprehensive end-to-end integration and analysis of HD cytometry data from different batches or experiments. Spectre streamlines the analytical stages of raw data pre-processing, batch alignment, data integration, clustering, dimensionality reduction, visualization, and population labelling, as well as quantitative and statistical analysis. Critically, the fundamental data structures used within Spectre, along with the implementation of machine learning classifiers, allow for the scalable analysis of very large HD datasets, generated by flow cytometry, mass cytometry, or spectral cytometry. Using open and flexible data structures, Spectre can also be used to analyze data generated by single-cell RNA sequencing or HD imaging technologies, such as Imaging Mass Cytometry. The simple, clear, and modular design of analysis workflows allow these tools to be used by bioinformaticians and laboratory scientists alike. Spectre is available as an R package or Docker container. R code is available on Github (https://github.com/immunedynamics/spectre).

Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance.

Abstract: Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980. Here, the authors profile the taxonomic composition and genetic potential of the gut microbiome of children with food or respiratory allergies and find that the gut metagenome of these patients is characterized by higher proinflammatory potential and reduced capacity of degrading complex polysaccharides, with Ruminococcus gnavus playing a central role.

Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.

Abstract: The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.