From human clinical discoveries
to translational research & discoveries

Our research program is framed around a translational approach, in which samples collected from children undergoing clinical care or enrolled in birth cohort studies are used to characterize the microbial alterations associated with human diseases, such as asthma, allergies and obesity. Our group also examines the causality and mechanisms of these associations in mouse models of inflammation, placing our work at a critical interface between clinical studies and experimental animal work.

projects DESCRIPTIONs

the early life mycobiome
in asthMA development

Erik V. Tilburg, PhD Std.

Expertises
Gnotobiotic Mice, Amplicon Sequencing, Metagenomics, Metabolomics, qPCR, Flow cytometry

Keywords
Early-life, mycobiome, Immune Development, Asthma, Airway Inflammation

Hypothesis
Early-life gut mycobiome alterations impact microbiome maturation & promote immunological changes that influence susceptibility to atopy & asthma.

The microbiome is causally implicated in immune development. Early-life use of antibiotics impacts the gut microbiome and can increase the risk of childhood atopy (allergy) and asthma. However, it is currently unknown if the fungal microbiome (mycobiome) contributes to antibiotic-induced dysbiosis. For this project, we sampled microbiome data from a human clinical study to determine the impact of antibiotics on the intestinal mycobiome of infants. Additionally, we colonized mice with specific fungal species expanded following antibiotic treatment, to determine the impact of fungi on mice immune system development and susceptibility to allergic airway inflammation (asthma models).

Thais Glatthardt , PDF

Expertises
Gnotobiotic mouse model, Flow cytometry, qPCR, plaque assay.

Keywords
Early life, RSV, Mycobiome, Gut-lung axis, Asthma

Hypothesis
Malassezia restricta gut colonization in early life impacts lung immune response against Respiratory Syncytial Virus and later asthma development

Respiratory syncytial virus (RSV) is a major cause of infant bronchiolitis and pneumonia worldwide and early-life RSV infection is associated with increased asthma risk. While the mechanisms involved in this connection are incompletely understood, the gut-lung axis is hypothesized to be involved given the roles of the gut microbiome in immune development, asthma risk, and lung immune responses to other respiratory viruses. While most microbiome studies are focused on gut bacteria, we and others have demonstrated that colonization with gut fungi potentiates mucosal and systemic immunity. Further, we recently showed that infant antibiotic use leads to an overgrowth of the fungi Malassezia restricta, and that colonization with this fungus increased susceptibility to allergic airway inflammation in mice. Thus, we hypothesized that colonization of M. restricta may also exacerbate inflammation after RSV infection and increase susceptibility to allergic airway inflammation post-infection.

the early life Microbiome
in NEUROdevelopment & Stress Axis

Emily Mercer, PhD Student

Expertises
Clinical Research, Metagenomics, Amplicon Sequencing, Metabolomics, Brain MRI, ELISA, R.

Keywords
Preterm Infants, Gut Microbiome, Early-Life, Chronic Stress, Gut-Brain Axis, Neurodevelopment, HPA Axis, Endocrinology

Hypothesis
The distinct patterns of gut microbiome maturation observed in infants born prematurely are bi-directionally linked to experiences of early-life stress, HPA-axis dysregulation, and brain connectivity in stress-related networks.

The gut microbiome and the brain communicate bidirectionally via several host- and microbially-derived signaling mechanisms, forming a critical biological axis. This includes via the hypothalamic-pituitary-adrenal (HPA) axis, which is the principal regulator of stress responses in the body through the transient release of glucocorticoids (e.g., cortisol) to influence numerous physiological processes, such as inflammation. In experimental animal models, the microbiome has been causally implicated in HPA axis programming in early life; however, our understanding of how this translates in humans remains limited. Given the gut microbiome and the brain undergo periods of rapid development in parallel in early life, and the gut-brain axis is increasingly recognized as a key mechanism by which the microbiome influences host development and health outcomes, this suggests a direct relationship exists between gut microbial colonization patterns and the programming of stress physiology in early life. The relationship between the gut microbiome and stress response development is of particular interest in infants born prematurely, as they face intensified alterations to microbial colonization patterns due to their unique early-life circumstances (e.g., higher rates of C-section, antibiotic exposure, physiological immaturities at birth) and experience developmentally unexpected stress throughout their stay in the NICU. In this project, we aim to generate a better understanding of the relationship between the gut microbiome and stress physiology in preterm infants by leveraging the Alberta BLOOM Study - a longitudinal birth cohort of preterm infants - to examine the relationship between the gut microbiome and cortisol measurements in the first 8 weeks of life and how this relates to the degree of stress infants experience in the NICU.

Van Ortega, PDF

Expertises
Cell isolation, Flow cytometry, MRI, High-throughput multiplex protein analysis, Cell culture, Confocal microscopy imaging, Histopathology, Endocrine assays, Behavioural testing

Keywords
Hypothalamic-Pituitary-Adrenal axis, Neurodevelopment, Early-life microbiome, Inflammation, Asthma, Endocrinology, Probiotics, Antibiotics, Chronic stress

Hypothesis
The early-life gut microbiome influences microglial development, HPA stress axis dysregulation and allergic asthma.

Early-life colonization of the gut by bacteria (i.e. the gut microbiome) influences the development and function of many physiological systems including the hypothalamic-pituitary-adrenal (HPA) stress axis, which itself is critical for regulating homeostasis in the body and the prevalence of peripheral inflammatory diseases, like asthma and stress-related anxiety disorders. Brain microglial cells are suspected to mediate this connection between the gut microbiome and the brain, whereby their over-activation causes stress-related disorders and cognitive deficits, and their elimination blocks anxiety recurrence and prevents excessive immune reactivity in the brain. Moreover, mice that lack a microbiome have microglia that are phenotypically different and have defective immune responses. However, the role that the microbiome plays in the early-life development of microglia and the HPA axis has not been tested in the context of its impact on asthma susceptibility. Examining the connection between two critical physiological systems in the body will be important to understanding how immune deficits are related to stress.

Kaetlyn Phillips, MSc Std.

Expertises
Gnotobiotic Mice, FMT, Amplicon Sequencing, Metagenomics, Metabolomics, CT, MRI, Immunofluo. imaging

Keywords
Early-life, Mycobiome, Immune Development, Asthma, Airway Inflammation

Hypothesis
Microbiome maturity driven by Bifidobacterium infantis is causally linked to improved neurodevelopmental measures in mice.

The early-life gut mycobiome
In Metabolic SyndromE

Mackenzie Guiterrez, PhD Std.

Expertises
Gnotobiotic Mice, Amplicon Sequencing, Metabolomics, Flow cytometry, TD-NMR, High-resolution Respirometry, qPCR

Keywords
Early-life, Mycobiome, Metabolism, Obesity, Inflammation, Immune-Metabolic interactions

Hypothesis
The early-life gut mycobiome influences the development of obesity and metabolic inflammation.

It has been previously established that the gut microbiome plays a crucial role the development of several host systems including metabolism and immunity. While the role of the bacterial community has been extensively investigated, the fungal population (mycobiome) remains understudied in this context. Given the connection between inflammation and metabolic disease and the potent ability of fungal colonizers to modulate the immune system, it is plausible that the early-life gut mycobiome is involve in this complex relationship. This project uses a combination of clinical findings and gnotobiotic mouse models to identify fungal species in the early-life gut mycobiome correlated with metabolic markers and causally investigate their role in disease development in mice.

early-life gut mycobiome
clinical studIES

Clinical Research (CR)Team
Andrea Guedez, CR lead
Allie McCraight, Adm CR
Alma T. Muropa, Biostat.Fatimoh Kasaba, Asst. CR

Expertises
NICUs & Peadiatrics clinical study visits, Biological sample Collection & Storage, Communication.

Keywords
Infancy, Longitudinal Cohort Studies, Human Samples, Biobanking, Microbial Research, Ecology, Early-Life Microbiome in Health & Diseases.

Hypothesis
Early-life Temporal Dynamics of the Human Gut Microbial Diversity, Composition and Co-occurrence Networks in a Rural District Setting

The Arrieta lab co-leads BLOOM, a prospective, longitudinal birth cohort study of premature infants born in Calgary called the Alberta BLOOM Study. This study follows premature infants from birth to three years of age, collecting comprehensive biological and clinical data that enables us to examine microbiome development during this period through a number of lenses. Given colonization patterns of the premature infant gut microbiome are known to differ from term-born infants, our goal is to better understand how these early alterations may impact infant development and long-term health outcomes, and to determine whether microbiome-based therapeutics may be employed to improve health outcomes in this population. More about BLOOM ? Visit our BLOOM website.

Mona Parizadeh, PDF

Expertises
R, Bash, Markdown, DADA2, QIIME, Mothur, SAMSA2, MetaPhlAn, HUMAnN, Bioconductor, Git, Galaxy, ARC, Compute Ca., Calcul QC, DNA & RNA Extraction, NGS, Amplicon Seq., Meta-'Omics.

Keywords
Microbial Ecology, Microbial Network Analysis, Cooccurrence Networks, Host-Microbe Interactions, Bioinformatics, Biostatistics, Meta'omics

Hypothesis
Early-life Temporal Dynamics of the Human Gut Microbial Diversity, Composition and Co-occurrence Networks in a Rural District Setting

Gut microbial colonization begins during birth and is highly heterogeneous until the age of 2-3 years. Many aspects of human development that rely on microbe-host and microbe-microbe interactions are affected by several factors, including social geography. Studies have shown that the microbial species richness in rural infants is greater than in urban infants. Yet, little is known about the early-life gut microbial composition in rural areas from less industrialized world regions. Moreover, our overall knowledge of the non-bacterial community composition is limited although microbial eukaryotes are increasingly recognized to have critical roles in ecosystem ecology and host crosstalk. To address these gaps, we characterize the bacterial and eukaryotic microbiomes in fecal samples from a longitudinal human cohort of nine children established in Morelos, Mexico, sampled monthly from birth until 18 months of age (average 14 samples/child). Using shotgun metagenomic and 18S rRNA sequencing, we study the bacterial and eukaryotic microbiomes and their co-occurrence networks in these samples in response to the mode of birth (vaginal vs c-section).

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From human clinical discoveries to translational research & discoveries

projects DESCRIPTIONs

the early life mycobiome in asthMA development

Expertises Gnotobiotic Mice, Amplicon Sequencing, Metagenomics, Metabolomics, qPCR, Flow cytometry

HypothesisEarly-life gut mycobiome alterations impact microbiome maturation & promote immunological changes that influence susceptibility to atopy & asthma.

Expertises Gnotobiotic mouse model, Flow cytometry, qPCR, plaque assay.

the early life Microbiome in NEUROdevelopment & Stress Axis

Expertises Clinical Research, Metagenomics, Amplicon Sequencing, Metabolomics, Brain MRI, ELISA, R.

Expertises Cell isolation, Flow cytometry, MRI, High-throughput multiplex protein analysis, Cell culture, Confocal microscopy imaging, Histopathology, Endocrine assays, Behavioural testing

Expertises Gnotobiotic Mice, FMT, Amplicon Sequencing, Metagenomics, Metabolomics, CT, MRI, Immunofluo. imaging

The early-life gut mycobiome In Metabolic SyndromE

Expertises Gnotobiotic Mice, Amplicon Sequencing, Metabolomics, Flow cytometry, TD-NMR, High-resolution Respirometry, qPCR

early-life gut mycobiome clinical studIES

Expertises NICUs & Peadiatrics clinical study visits, Biological sample Collection & Storage, Communication.

Expertises R, Bash, Markdown, DADA2, QIIME, Mothur, SAMSA2, MetaPhlAn, HUMAnN, Bioconductor, Git, Galaxy, ARC, Compute Ca., Calcul QC, DNA & RNA Extraction, NGS, Amplicon Seq., Meta-'Omics.