The Gut Microbiome, Microbial Metabolites, and Cardiovascular Disease in People Living with HIV

Peters, Brandilyn A.; Burk, Robert D.; Kaplan, Robert C.; Qi, Qibin

doi:10.1007/s11904-023-00648-y

Cited by 9 publications

(7 citation statements)

References 114 publications

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“…43 Further research suggests that a direct correlation also exists between the levels of phenylacetylglutamine and NT-proBNP in patients with heart failure. 5,36 A metabolomic profiling study in patients with cardiac fibrosis and steatosis with risk for HIV 44 and patients with HIV and CVD 45 showed high levels of PAGln. Laboratory investigations using heart failure mice show an enhanced activation of the TLR4/AKT/mTOR signaling pathway by PAGln in in vitro and in vivo study.…”

Section: ■ Phenylacetylglutamine In Cardiovascular Diseasesmentioning

confidence: 99%

“…Heart failure patients with high plasma phenylalanine levels also had high levels of C-reactive proteins (CRP) and inflammatory cytokines (IL-8, IL-10), which is also reported to correlate with mortality among the critically ill patients . Further research suggests that a direct correlation also exists between the levels of phenylacetylglutamine and NT-proBNP in patients with heart failure. , A metabolomic profiling study in patients with cardiac fibrosis and steatosis with risk for HIV and patients with HIV and CVD showed high levels of PAGln.…”

Section: Phenylacetylglutamine In Cardiovascular Diseasesmentioning

confidence: 99%

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Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Krishnamoorthy,

Kalyan,

Hediyal

et al. 2024

ACS Omega

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Over the past few decades, it has been well established that gut microbiotaderived metabolites can disrupt gut function, thus resulting in an array of diseases. Notably, phenylacetylglutamine (PAGln), a bacterial derived metabolite, has recently gained attention due to its role in the initiation and progression of cardiovascular and cerebrovascular diseases. This meta-organismal metabolite PAGln is a byproduct of amino acid acetylation of its precursor phenylacetic acid (PAA) from a range of dietary sources like egg, meat, dairy products, etc. The microbiota-dependent metabolism of phenylalanine produces PAA, which is a crucial intermediate that is catalyzed by diverse microbial catalytic pathways. PAA conjugates with glutamine and glycine in the liver and kidney to predominantly form phenylacetylglutamine in humans and phenylacetylglycine in rodents. PAGln is associated with thrombosis as it enhances platelet activation mediated through the GPCRs receptors α2A, α2B, and β2 ADRs, thereby aggravating the pathological conditions. Clinical evidence suggests that elevated levels of PAGln are associated with pathology of cardiovascular, cerebrovascular, and neurological diseases. This Review further consolidates the microbial/biochemical synthesis of PAGln and discusses its role in the above pathophysiologies.

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Section: ■ Phenylacetylglutamine In Cardiovascular Diseasesmentioning

confidence: 99%

Section: Phenylacetylglutamine In Cardiovascular Diseasesmentioning

confidence: 99%

Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Krishnamoorthy,

Kalyan,

Hediyal

et al. 2024

ACS Omega

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“…242 These studies have provided inconsistent evidence, and are limited by cross-sectional designs and a sole-focus on the gut-microbiota-related metabolite trimethylamine-N-oxide. 242 Still, higher trimethylamine-N-oxide has been associated with an increased risk of incident carotid plaque in PLWH over a 7-year follow-up period, and this association was attenuated upon adjustment for sCD14 and sCD163 suggesting a potential role for microbial-mediated monocyte activation. 243 Further, a small but growing body of translational evidence has indicated that gut microbial diversity and intestinal permeability contribute to age-related vascular dysfunction in people without HIV.…”

Section: Hiv Gut Dysbiosis and Host Immune Cell Interactionsmentioning

confidence: 99%

“…239 At present, few studies have specifically examined the role of the gut microbiome in vascular dysfunction among PLWH. 242 These studies have provided inconsistent evidence, and are limited by cross-sectional designs and a sole-focus on the gut-microbiota-related metabolite trimethylamine-N-oxide. 242 Still, higher trimethylamine-N-oxide has been associated with an increased risk of incident carotid plaque in PLWH over a 7-year follow-up period, and this association was attenuated upon adjustment for sCD14 and sCD163 suggesting a potential role for microbial-mediated monocyte activation.…”

Section: Hiv Gut Dysbiosis and Host Immune Cell Interactionsmentioning

confidence: 99%

Exercise to Prevent Accelerated Vascular Aging in People Living With HIV

Jones,

Robinson,

Beach

et al. 2024

Circulation Research

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Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.

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“…The widespread use of antiretroviral therapy (ART) has improved the health of persons with HIV, including younger people who may be more prone to certain HIVrelated disorders such as microbial translocation resulting from alterations in intestinal gut integrity [1,2]. Although HIV viral suppression (<1000 copies/ml) is achieved in a majority of children with perinatally acquired HIV on ART, gut integrity is not fully restored, allowing continuous intestinal barrier damage that results in suboptimal global inflammation and metabolic imbalances [3,4].…”

mentioning

confidence: 99%

HIV-related gut damage persists long-term in perinatally acquired HIV and is associated with insulin resistance

Abdel-Hameed,

Masenga

2024

Aids

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The Gut Microbiome, Microbial Metabolites, and Cardiovascular Disease in People Living with HIV

Cited by 9 publications

References 114 publications

Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Role of the Gut Bacteria-Derived Metabolite Phenylacetylglutamine in Health and Diseases

Exercise to Prevent Accelerated Vascular Aging in People Living With HIV

HIV-related gut damage persists long-term in perinatally acquired HIV and is associated with insulin resistance

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