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Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection
Weill-Cornell Cellular Immunology Laboratory, Division of Hematology/Oncology, Host Defenses Program, Department of Pediatrics, Weill Medical College of Cornell University (WCUMC), New York, NY 10065, USA
Department of Food Technology, Lund University, Lund SE-221 00, Sweden
Division of Infectious Disease, Department of Pediatrics, Weill Medical College of Cornell University (WCUMC), New York, NY 10065, USA
Division of Surgery and Interventional Science, University College London, 74 Huntley Street, London WC1E 6AU, UK
Current address: Health Resources and Services Administration, Department of Health and Human Services, Washington, DC 20201, USA.
This author is an employee of the United States Department of Health and Human Services. The positions expressed and recommendations made in this paper do not necessarily represent those of the United States Government.
Current address: Cedars-Sinai Medical Group, Los Angeles, CA 90048, USA.
Current address: Columbia University School of Nursing, New York, NY 10032, USA.
Current address: Albert Einstein College of Medicine, Hofstra North Shore-LIJ School of Medicine, 9 Pine Drive North, Roslyn, NY 11576, USA.
* Author to whom correspondence should be addressed.
Received: 28 September 2011; in revised form: 24 November 2011 / Accepted: 5 December 2011 / Published: 19 December 2011
Abstract: The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1) infection to the Acquired Immunodeficiency Syndrome (AIDS) was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT) for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg) cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART) has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to formula alone. Pilot studies have shown that probiotic bacteria given as a supplement have improved growth and protected against loss of CD4+ T cells. The recognition that normal bacterial flora prime neonatal immune response and that abnormal flora have a profound impact on metabolism has generated insight into potential mechanisms of gut dysfunction in many settings including HIV-1 infection. As discussed here, current and emerging studies support the concept that probiotic bacteria can provide specific benefit in HIV-1 infection. Probiotic bacteria have proven active against bacterial vaginosis in HIV-1 positive women and have enhanced growth in infants with congenital HIV-1 infection. Probiotic bacteria may stabilize CD4+ T cell numbers in HIV-1 infected children and are likely to have protective effects against inflammation and chronic immune activation of the gastrointestinal immune system.
Keywords: microbial translocation; inflammation; probiotic bacteria; lactobacillus; HIV-1; AIDS; children; women; anti retroviral therapy; growth; failure-to-thrive; gut associated lymphoid tissue (GALT); mucosal barrier; microflora; CD4+ Th17 cells; CD4+ CD25+ FoxP3+ T regulatory cells; immune development; micronutrient; nutrition; body mass index (BMI); body cellular mass; BCM; anti-retroviral therapy (ART)
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Cunningham-Rundles, S.; Ahrné, S.; Johann-Liang, R.; Abuav, R.; Dunn-Navarra, A.-M.; Grassey, C.; Bengmark, S.; Cervia, J.S. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection. Nutrients 2011, 3, 1042-1070.
Cunningham-Rundles S, Ahrné S, Johann-Liang R, Abuav R, Dunn-Navarra A-M, Grassey C, Bengmark S, Cervia JS. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection. Nutrients. 2011; 3(12):1042-1070.
Cunningham-Rundles, Susanna; Ahrné, Siv; Johann-Liang, Rosemary; Abuav, Rachel; Dunn-Navarra, Ann-Margaret; Grassey, Claudia; Bengmark, Stig; Cervia, Joseph S. 2011. "Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection." Nutrients 3, no. 12: 1042-1070.