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      Synbiotic therapy decreases microbial translocation and inflammation and improves immunological status in HIV-infected patients: a double-blind randomized controlled pilot trial

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          Abstract

          Background

          HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production.

          Methods

          A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks.

          Results

          We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma ( p = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces ( p = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium; p = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p = 0.05) and the level of Interleukin 6 cytokine decreased significantly ( p = 0.016).

          Conclusions

          Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources.

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          Most cited references32

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          Probiotics and their fermented food products are beneficial for health.

          Probiotics are usually defined as microbial food supplements with beneficial effects on the consumers. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks or other fermented foods. Some of the beneficial effect of lactic acid bacteria consumption include: (i) improving intestinal tract health; (ii) enhancing the immune system, synthesizing and enhancing the bioavailability of nutrients; (iii) reducing symptoms of lactose intolerance, decreasing the prevalence of allergy in susceptible individuals; and (iv) reducing risk of certain cancers. The mechanisms by which probiotics exert their effects are largely unknown, but may involve modifying gut pH, antagonizing pathogens through production of antimicrobial compounds, competing for pathogen binding and receptor sites as well as for available nutrients and growth factors, stimulating immunomodulatory cells, and producing lactase. Selection criteria, efficacy, food and supplement sources and safety issues around probiotics are reviewed. Recent scientific investigation has supported the important role of probiotics as a part of a healthy diet for human as well as for animals and may be an avenue to provide a safe, cost effective, and 'natural' approach that adds a barrier against microbial infection. This paper presents a review of probiotics in health maintenance and disease prevention.
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            Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces.

            16S rRNA gene-targeted group-specific primers were designed and validated for specific detection and quantification of the Clostridium leptum subgroup and the Atopobium cluster. To monitor the predominant bacteria in human feces by real-time PCR, we used these specific primers together with four sets of group-specific primers for the Clostridium coccoides group, the Bacteroides fragilis group, Bifidobacterium, and Prevotella developed in a previous study (T. Matsuki, K. Watanabe, J. Fujimoto, Y. Miyamoto, T. Takada, K. Matsumoto, H. Oyaizu, and R. Tanaka, Appl. Environ. Microbiol. 68:5445-5451, 2002). Examination of DNA extracted from the feces of 46 healthy adults showed that the C. coccoides group was present in the greatest numbers (log10 10.3 +/- 0.3 cells per g [wet weight] [average +/- standard deviation]), followed by the C. leptum subgroup (log10 9.9 +/- 0.7 cells per g [wet weight]), the B. fragilis group (log10 9.9 +/- 0.3 cells per g [wet weight]), Bifidobacterium (log10 9.4 +/- 0.7 cells per g [wet weight]), and the Atopobium cluster (log10 9.3 +/- 0.7 cells per g [wet weight]). These five bacterial groups were detected in all 46 volunteers. Prevotella was found in only 46% of the subjects at a level of log10 9.7 +/- 0.8 cells per g (wet weight). Examination of changes in the population and the composition of the intestinal flora for six healthy adults over an 8-month period revealed that the composition of the flora of each volunteer remained stable throughout the test period.
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              Microbial translocation is a cause of systemic immune activation in chronic HIV infection

              Chronic activation of the immune system is a hallmark of progressive HIV infection and better predicts disease outcome than plasma viral load, yet its etiology remains obscure. Here, we show that circulating microbial products, likely derived from the gastrointestinal tract, are a primary cause of HIV-related systemic immune activation. Circulating lipopolysaccharide, an indicator of microbial translocation, is significantly increased in chronically HIV-infected individuals and SIV-infected rhesus macaques. We show that monocytes are chronically stimulated in vivo by increased lipopolysaccharide, which also correlates with measures of innate and adaptive immune activation. Effective antiretroviral therapy appears to reduce microbial translocation. Furthermore, in non-pathogenic SIV infection of sooty mangabeys, microbial translocation does not seem to occur. These data establish a mechanism for chronic immune activation in the context of a compromised gastrointestinal mucosal surface and provide novel directions for therapeutic interventions that modify the consequences of acute HIV infection.
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                Author and article information

                Journal
                Nutr J
                Nutr J
                Nutrition Journal
                BioMed Central
                1475-2891
                2012
                29 October 2012
                : 11
                : 90
                Affiliations
                [1 ]HIV Unit Hospital Civil de Guadalajara “Fray Antonio Alcalde”, University of Guadalajara, Calle Hospital 278, Colonia Alcalde Barranquitas, Guadalajara, Jalisco, 44280, Mexico
                [2 ]Centro Universitario de Ciencias de la Salud (CUCS), UdeG, Guadalajara, Jalisco, Mexico
                [3 ]Centro de Investigación Biomédicas de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara, Jalisco, Mexico
                Article
                1475-2891-11-90
                10.1186/1475-2891-11-90
                3494555
                23101545
                68a6bef9-15b7-4285-97df-bcbf40088ace
                Copyright ©2012 González-Hernández et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 March 2012
                : 25 October 2012
                Categories
                Research

                Nutrition & Dietetics
                Nutrition & Dietetics

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