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: 3.99). 03/2008; 46(2):757-8. DOI: 10.1128/JCM.01729-07
Source: PubMed


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.

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    • "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]. "
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    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(3):803185. DOI:10.1155/2014/803185 · 1.75 Impact Factor
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    • "The gastrointestinal tract is a primary target organ for human immunodeficiency virus (HIV).1–3 The virus predominantly replicates in CD4+ T-cells in lymphoid tissues, and the gastrointestinal tract contains up to 70%–90% of all lymphocytes in the body.1–3 "
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    ABSTRACT: Background The gastrointestinal tract is a primary target for human immunodeficiency virus (HIV). HIV infection causes a depletion of CD4+ T-lymphocytes in gut-associated lymphoid tissue and affects gastrointestinal mucosal integrity and permeability. The gastrointestinal tract has also been suggested as the main reservoir of HIV despite highly active antiretroviral therapy (HAART). We performed a prospective case-control study to assess gut involvement in HIV-infected patients, either naïve or on HAART, using noninvasive methods such as bowel ultrasound and fecal calprotectin. Methods Thirty HIV-infected children and youth underwent the following tests: CD4+ T-cell count and HIV viral load, fecal calprotectin, and bowel ultrasound, with the latter evaluating bowel wall thickness and mesenteric lymph nodes. Fecal calprotectin and bowel ultrasound were also assessed in 30 healthy controls matched for age and sex. Fecal calprotectin was measured using a quantitative immunochromatographic point-of-care test, and concentrations ranging from 0 to 200 μg/g were considered to be normal reference values in children. Results Fecal calprotectin was normal in 29 HIV-infected patients and was not significantly different from controls (mean values 63.8±42.5 μg/g and 68.3±40.5 μg/g, respectively; P=0.419), and did not correlate with HIV viral load, CD4+ T-cell absolute count and percentage, or HAART treatment. No significant changes were found on bowel ultrasound except for enlarged mesenteric lymph nodes, which were observed in seven HIV-infected patients (23.3%) and two controls (6.6%). This finding was significantly correlated with high HIV viral load (P=0.001) and low CD4+ T-cell percentage (P=0.004). Conclusion HIV-infected children did not have significant biochemical or ultrasonographic signs of bowel inflammation. A few patients showed enlarged mesenteric lymph nodes, which correlated with uncontrolled HIV infection.
    HIV/AIDS - Research and Palliative Care 05/2014; 6:69-74. DOI:10.2147/HIV.S60157
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    • "The gut is another major site of polymicrobial colonization and infection. In early stages of HIV infection, the composition of the gut microbiota changes, and increased inflammation in the gastrointestinal (GI) tract leads to damage of the mucosal barrier (67). Breakdown of the intestinal barrier allows microbial LPS to enter the blood and results in chronic immune activation, a commonly observed feature of HIV infection and a contributor to the progression to AIDS (68, 69). "
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    ABSTRACT: ABSTRACT The human body plays host to a wide variety of microbes, commensal and pathogenic. In addition to interacting with their host, different microbes, such as bacteria and viruses, interact with each other, sometimes in ways that exacerbate disease. In particular, gene expression of a number of viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV), is known to be regulated by epigenetic modifications induced by bacteria. These viruses establish latent infection in their host cells and can be reactivated by bacterial products. Viral reactivation has been suggested to contribute to periodontal disease and AIDS. In addition, bacterium-virus interactions may play a role in cancers, such as Kaposi's sarcoma, gastric cancer, and head and neck cancer. It is important to consider the effects of coexisting bacterial infections when studying viral diseases in vivo.
    mBio 04/2014; 5(3). DOI:10.1128/mBio.01015-14 · 6.79 Impact Factor
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