HIV-associated changes in the enteric microbial community: potential role in loss of homeostasis and development of systemic inflammation

Gootenberg, David B.; Paer, Jeffrey M.; Luevano, Jesus-Mario; Kwon, Douglas S.

doi:10.1097/qco.0000000000000341

Cited by 83 publications

(48 citation statements)

References 207 publications

(320 reference statements)

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“…Our finding is important because a growing number of studies indicate that IBD patients have an increased risk of developing cardiovascular disease, especially during flare-ups ( 101 , 102 ). The mechanisms underlying this increased risk are not well resolved but may relate to a proposed explanation for the increased cardiovascular disease risk observed in HIV-infected patients ( 103 , 104 ). In this model, changes in the relative proportions of protective and pathobiotic gut microbiota, especially those capable of translocating across the gut epithelium, activate a chronic systemic inflammation that increases cardiovascular disease risk.…”

Section: Discussionmentioning

confidence: 99%

Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice

et al. 2017

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IBD patients harbor distinct microbial communities with functional capabilities different from those seen with healthy people. But is this cause or effect? Answering this question requires data on changes in gut microbial communities leading to disease onset. By performing weekly metagenomic sequencing and mixed-effects modeling on an established mouse model of IBD, we identified several functional pathways encoded by the gut microbiome that covary with host immune status. These pathways are novel early biomarkers that may either enable microbes to live inside an inflamed gut or contribute to immune activation in IBD mice. Future work will validate the potential roles of these microbial pathways in host-microbe interactions and human disease. This study was novel in its longitudinal design and focus on microbial pathways, which provided new mechanistic insights into the role of gut microbes in IBD development.

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Section: Discussionmentioning

confidence: 99%

Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice

et al. 2017

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“…It remains uncertain whether induction of HDB2 expression in vivo would be beneficial and reduce viral burden. However, induction of this antiviral peptide by bacterial products such as LPS may exacerbate the chronic inflammation and inflammation related diseases observed in HIV-1 infected individuals [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Early type I Interferon response induces upregulation of human β-defensin 1 during acute HIV-1 infection

et al. 2017

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HIV-1 is able to evade innate antiviral responses during acute infection to establish a chronic systemic infection which, in the absence of antiretroviral therapy (ART), typically progresses to severe immunodeficiency. Understanding these early innate immune responses against HIV-1 and their mechanisms of failure is relevant to the development of interventions to better prevent HIV-1 transmission. Human beta defensins (HBDs) are antibacterial peptides but have recently also been associated with control of viral replication. HBD1 and 2 are expressed in PBMCs as well as intestinal tissue, but their expression in vivo during HIV-1 infection has not been characterized. We demonstrate that during acute HIV-1 infection, HBD1 but not HBD2 is highly upregulated in circulating monocytes but returns to baseline levels during chronic infection. HBD1 expression in monocytes can be induced by HIV-1 in vitro, although direct infection may not entirely account for the increase in HBD1 during acute infection. We provide evidence that HIV-1 triggers antiviral IFN-α responses, which act as a potent inducer of HBD1. Our results show the first characterization of induction of an HBD during acute and chronic viral infection in humans. HBD1 has been reported to have low activity against HIV-1 compared to other defensins, suggesting that in vivo induced defensins may not significantly contribute to the robust early antiviral response against HIV-1. These data provide important insight into the in vivo kinetics of HBD expression, the mechanism of HBD1 induction by HIV-1, and the role of HBDs in the early innate response to HIV-1 during acute infection.

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“…These findings suggest that virome expansion is linked to the pathogenesis of AIDS and highlights the role of the immune system in controlling viral populations in the intestine ( Monaco et al, 2016 ). In addition, enteric viral communities have been found to change during HIV infection and raises in Anelloviridae and other virus titers have been associated to increased pathology ( Gootenberg et al, 2017 ).…”

Section: The Human Viromementioning

confidence: 99%

The Virome and Its Major Component, Anellovirus, a Convoluted System Molding Human Immune Defenses and Possibly Affecting the Development of Asthma and Respiratory Diseases in Childhood

et al. 2018

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The microbiome, a thriving and complex microbial community colonizing the human body, has a broad impact on human health. Colonization is a continuous process that starts very early in life and occurs thanks to shrewd strategies microbes have evolved to tackle a convoluted array of anatomical, physiological, and functional barriers of the human body. Cumulative evidence shows that viruses are part of the microbiome. This part, called virome, has a dynamic composition that reflects what we eat, how and where we live, what we do, our genetic background, and other unpredictable variables. Thus, the virome plays a chief role in shaping innate and adaptive host immune defenses. Imbalance of normal microbial flora is thought to trigger or exacerbate many acute and chronic disorders. A compelling example can be found in the respiratory apparatus, where early-life viral infections are major determinants for the development of allergic diseases, like asthma, and other non-transmissible diseases. In this review, we focus on the virome and, particularly, on Anelloviridae, a recently discovered virus family. Anelloviruses are major components of the virome, present in most, if not all, human beings, where they are acquired early in life and replicate persistently without causing apparent disease. We will discuss how modulation of innate and adaptive immune systems by Anelloviruses can influence the development of respiratory diseases in childhood and provide evidence for the use of Anelloviruses as useful and practical molecular markers to monitor inflammatory processes and immune system competence.

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HIV-associated changes in the enteric microbial community: potential role in loss of homeostasis and development of systemic inflammation

Abstract: Supplemental Digital Content is available in the text

Cited by 83 publications

References 207 publications

Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice

Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice

Early type I Interferon response induces upregulation of human β-defensin 1 during acute HIV-1 infection

The Virome and Its Major Component, Anellovirus, a Convoluted System Molding Human Immune Defenses and Possibly Affecting the Development of Asthma and Respiratory Diseases in Childhood

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