Early Impairment of Gut Function and Gut Flora Supporting a Role for Alteration of Gastrointestinal Mucosa in Human Immunodeficiency Virus Pathogenesis

Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Via Solferino 16-20052, Milan, Italy.
Journal of clinical microbiology (Impact Factor: 4.23). 03/2008; 46(2):757-8. DOI: 10.1128/JCM.01729-07
Source: PubMed

ABSTRACT Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the hypothesis that alterations at the gastrointestinal-tract level are a key factor in HIV pathogenesis.

  • Source
    • "This is based on findings associating the resident bacteria with immune activation. As such, studies have been ascribed to certain bacterial species, roles in maintaining epithelial mucosal integrity [40], and the early maturation of the adaptive immune system [7] [21], and these are being exploited in progut formulations [41]. HIV subjects are known to have a compromised gut barrier function and the observation that Bifidobacterium and Lactobacillus species are depleted among the gut bacteria populations in such patients [23] is consistent with earlier studies attributing improved gut barrier and immune function to these species [42]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Survival rates among HIV patients have significantly improved since the introduction of antiretroviral therapy (ART) in HIV management. However, persistent disease progression and clinical complications in virally suppressed individuals point to additional contributing factors other than HIV replication; microbial translocation is one such factor. The role of underlying commensal microbes and microbial products that traverse the intestinal lumen into systemic circulation in the absence of overt bacteraemia is under current investigation. This review focuses on current knowledge of the complex microbial communities and microbial markers involved in the disruption of mucosal immune T-cells in the promotion of inflammatory processes in HIV infections. Unanswered questions and aims for future studies are addressed. We provide perspective for discussing potential future therapeutic strategies focused on modulating the gut microbiota to abate HIV disease progression.
    Gastroenterology Research and Practice 06/2014; 2014:803185. DOI:10.1155/2014/803185 · 1.75 Impact Factor
  • Source
    • "This loss of Th17 cells leads to even more microbial translocation, and the cycle continues (Favre et al., 2010). HIV disease disrupts the normal microbiota of the gut (dysbiosis ) (Ellis et al., 2011; Gori et al., 2008; Vujkovic-Cvijin et al., 2013). This process is associated with an enrichment of bacterial species that can catabolize tryptophan through the kynurenine pathway, which may contribute to the loss of Th17 cells (Vujkovic-Cvijin et al., 2013), as noted above. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging.
    Immunity 10/2013; 39(4):633-45. DOI:10.1016/j.immuni.2013.10.001 · 19.75 Impact Factor
  • Source
    • "It will be important to determine whether Sarcina and Staphylococci, which also bloomed in the other SIVcpz-positive chimpanzees (who have remained asymptomatic as of this writing), might be an early predictor of subsequent immune deterioration. By tracking the microbiota of individual chimpanzees that became naturally infected by SIVcpz during the course of natural history studies, we identified effects of SIVcpz infection on the gut microbiome that have previously gone unrecognized by comparisons of HIV-1-infected and uninfected humans (Ellis et al., 2011; Gori et al., 2008) or of SIV-infected and uninfected monkeys (Handley et al., 2012; McKenna et al., 2008). However, we were not able to explicitly correlate immune decline in SIVcpz-infected chimpanzees with gut microbiota composition, and as such, we cannot rule out the possibility that the changes in the gut microbiota we observed were mediated by other unmeasured factors. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Simian immunodeficiency virus of chimpanzees (SIVcpz) is the ancestor of human immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS) in humans. Like HIV-1-infected humans, SIVcpz-infected chimpanzees can develop AIDS-like symptoms. Because SIVcpz/HIV-1 may disrupt regulation of the gut microbiome and because it has not been possible to sample individual humans pre- and postinfection, we investigated the influence of infection on gut communities through long-term monitoring of chimpanzees from Gombe National Park, Tanzania. SIVcpz infection accelerated the rate of change in gut microbiota composition within individuals for periods of years after the initial infection and led to gut communities marked by high frequencies of pathogen-containing bacterial genera absent from SIVcpz-negative individuals. Our results indicate that immune function maintains temporally stable gut communities that are lost when individuals become infected with SIVcpz.
    Cell host & microbe 09/2013; 14(3):340-5. DOI:10.1016/j.chom.2013.08.005 · 12.19 Impact Factor
Show more