Research Team
Barbara Swanson, Principal Investigator, RUSH University College of Nursing
Louis Fogg, Investigator, RUSH University College of Nursing
Wrenetha Julion, Co-Investigator, RUSH University College of Nursing
Ali Keshavarzian, Co-Investigator, RUSH Medical College
Funding Source
RUSH College of Nursing Faculty Pilot Grant
Award Period
4/1/19 - 9/30/20
Abstract
We are proposing to test the validity of digital photography as a measure of adherence to dietary supplements in African American (AA) men. This pilot study will inform a subsequent application to the National Institute for Nursing Research (NINR) to test the efficacy of a prebiotic dietary supplement against a placebo control group to favorably modulate the gut microbiome of African American (AA) men with metabolic syndrome (MetS). African American men are disproportionately affected by metabolic syndrome (MetS) and, accordingly, show higher rates of cardiovascular disease and sudden cardiac arrest compared to other racial groups.
Emerging evidence implicates gut bacteria in the pathogenesis of MetS and its sequelae. The composition of the residential gut bacteria, known as the gut microbiota, modulates systemic biological processes and disruptions in microbial communities, known as dysbiosis, are associated with metabolic and inflammatory diseases. AA A growing body of animal and human research suggests that he HIV infection is associated with the premature onset of age-associated co-morbidities such as non-AIDS malignancies and cardiovascular disease. These co-morbidities have been linked to persistently elevated serum levels of proinflammatory cytokines that mimic an aging phenotype known as "inflamm-aging." In both middle-aged HIV+ persons and older HIV seronegative adults, inflamm-aging is associated with more limited T cell repertoires and increased risk for morbidities and mortality.
Our hypothesis is that inflamm-aging is responsible for the premature immune senescence associated with HIV infection in aging individuals. Immune senescence, characterized by diminished replicative capacity, has been observed in middle-aged persons treated with highly active antiretroviral therapy (H/VKRT) who achieve immune reconstitution and undetectable viral loads. Senescent cells are characterized by the absence of the surface marker CD28, and in advanced senescence express CD57 (CD28-/CD57+ phenotype). Fish oil may be an effective treatment option for reducing HIV-related inflamm-aging. Cold water fish are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory effects.
We propose a 12-week, randomized, double-blind, placebo-controlled trial to explore the safety and estimate the effect size of fish oil to modulate parameters of inflamm-aging and immune senescence in a well-characterized cohort of 38 HIV+ AA. Participants will be between the ages of 50 and 65, on stable HAART, and with inflammation evidenced by elevated plasma concentrations of interleukln-6 (IL-6) or high sensitivity C-reactive protein (hsCRP). Participants will be recruited from the Rush Center of Excellence on Disparities in HIV and Aging (Rush CEDHA). Each participant will be randomized to receive either 1.2 grams daily of EPA and DHA (600 mg of EPA and 600 mg of DHA), or a placebo identical in appearance for 12 weeks. We will measure (a) soluble markers of inflammation: TNF-alpha, lL-6, and gamma IFN; and (b) markers of immune senescence: CD28 and CD57 expression on CD8+ and CD4+ T lymphocyte cells. At baseline and 4 and 12 weeks post-baseline, we will measure safety parameters.