Angela Sofia Burkhart Colorado

University of Colorado Denver

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Casey Martin

HCA Healthcare

Catherine Lozupone

University of Colorado Anschutz Medical Campus

Alessandro Lazzaro

Sapienza University of Rome

Kathryn Boyd

University of London

Thomas Campbell

University of Colorado Anschutz Medical Campus

Janet Siebert

University of Colorado Anschutz Medical Campus

Nichole Nusbacher

University of Colorado Anschutz Medical Campus

Brent E. Palmer

University of Colorado Anschutz Medical Campus

Margaret Borok

University of Zimbabwe

Suzanne Fiorillo

University of Colorado Anschutz Medical Campus

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University of Colorado Anschutz Medical Campus

University of Colorado Denver

Sapienza University of Rome

University of Zimbabwe

London School of Hygiene & Tropical Medicine

Color (United States)

University of Colorado Boulder

University of Colorado System

University of Wisconsin–Madison

University of California, Berkeley

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Antiretroviral treatment is less effective at reducing gut microbiome-associated inflammation and T cell activation in people living with HIV in rural versus urban Zimbabwe

Research Square (Research Square) (2023)

Alessandro Lazzaro Angela Sofia Burkhart Colorado C. Preston Neff Nichole Nusbacher Kathryn Boyd

The widespread availability of antiretroviral therapy (ART) for people living with HIV (PLWH) has dramatically reduced mortality and improved life expectancy. However, even with suppression of HIV-1 replication, chronic immune activation and elevated inflammation persist. Chronic immune activation has been linked to a pro-inflammatory gut microbiome composition, exacerbated by compromised intestinal barrier integrity that occurs after HIV infection. Individuals living in urban versus rural areas of sub-Saharan Africa have differences in environmental factors such as water source or diet that may impact gut microbiome composition, yet immune phenotype and gut microbiome composition response to ART in PLWH living in rural versus urban areas of sub-Saharan Africa have not been compared. Here, we measured immune phenotypes and fecal microbiome composition in PLWH and healthy participants recruited from the urban Mabvuku polyclinic in the city of Harare, Zimbabwe and the Mutoko District hospital located in a district 146 km from Harare that services surrounding rural villages. PLWH were either ART naïve at baseline and sampled again after 24 weeks of treatment with efavirenz/lamivudine/tenofovir disoproxil fumarate (EFV/3TC/TDF) and the prophylactic antibiotic cotrimoxazole or were ART experienced at both timepoints. Although expected reductions in the inflammatory marker IL-6, T-cell activation, and exhaustion were observed in individuals who had suppressed HIV-1 with treatment, these changes were significant only when considering individuals in the urban and not the rural area. Gut microbiome composition showed more marked differences from healthy controls in the ART experienced compared to ART naïve cohort, and consistent longitudinal changes were also observed in ART naïve PLWH after 24 weeks of treatment, including a reduction in alpha diversity and altered composition. However, gut microbiome composition showed a more pronounced relationship with chronic immune activation and exhaustion phenotypes in the ART naïve compared to ART experienced PLWH, suggesting a particularly significant role for the gut microbiome in disease progression in uncontrolled infection.

Efavirenz

Immune Dysregulation

10.21203/rs.3.rs-3300723/v1

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Integrating biological knowledge for mechanistic inference in the host-associated microbiome

Frontiers in Microbiology (2024)

Brook Santangelo Madison Apgar Angela Sofia Burkhart Colorado Casey Martin John D. Sterrett

Advances in high-throughput technologies have enhanced our ability to describe microbial communities as they relate to human health and disease. Alongside the growth in sequencing data has come an influx of resources that synthesize knowledge surrounding microbial traits, functions, and metabolic potential with knowledge of how they may impact host pathways to influence disease phenotypes. These knowledge bases can enable the development of mechanistic explanations that may underlie correlations detected between microbial communities and disease. In this review, we survey existing resources and methodologies for the computational integration of broad classes of microbial and host knowledge. We evaluate these knowledge bases in their access methods, content, and source characteristics. We discuss challenges of the creation and utilization of knowledge bases including inconsistency of nomenclature assignment of taxa and metabolites across sources, whether the biological entities represented are rooted in ontologies or taxonomies, and how the structure and accessibility limit the diversity of applications and user types. We make this information available in a code and data repository at: https://github.com/lozuponelab/knowledge-source-mappings . Addressing these challenges will allow for the development of more effective tools for drawing from abundant knowledge to find new insights into microbial mechanisms in disease by fostering a systematic and unbiased exploration of existing information.

Human Microbiome Project

10.3389/fmicb.2024.1351678

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Differential effects of antiretroviral treatment on immunity and gut microbiome composition in people living with HIV in rural versus urban Zimbabwe

Microbiome (2024)

Angela Sofia Burkhart Colorado Alessandro Lazzaro C. Preston Neff Nichole Nusbacher Kathryn Boyd

The widespread availability of antiretroviral therapy (ART) has dramatically reduced mortality and improved life expectancy for people living with HIV (PLWH). However, even with HIV-1 suppression, chronic immune activation and elevated inflammation persist and have been linked to a pro-inflammatory gut microbiome composition and compromised intestinal barrier integrity. PLWH in urban versus rural areas of sub-Saharan Africa experience differences in environmental factors that may impact the gut microbiome and immune system, in response to ART, yet this has not previously been investigated in these groups. To address this, we measured T cell activation/exhaustion/trafficking markers, plasma inflammatory markers, and fecal microbiome composition in PLWH and healthy participants recruited from an urban clinic in the city of Harare, Zimbabwe, and a district hospital that services surrounding rural villages. PLWH were either ART naïve at baseline and sampled again after 24 weeks of first-line ART and the antibiotic cotrimoxazole or were ART-experienced at both timepoints.

Immune Dysregulation

10.1186/s40168-023-01718-4

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Citations (6)