Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection

Siv Ahrné,Stig Bengmark,Rosemary Johann-Liang,Susanna Cunningham-Rundles,Rachel Abuav,Claudia Grassey,Ann-Margaret Dunn-Navarra,Joseph S. Cervia

doi:10.3390/nu3121042

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.

Highlights

The original perception that intestinal mucosal starvation could be a central cause of the mucosal atrophy, opportunistic bacterial growth, and microbial translocation in untreated Human Immunodeficiency Virus type1 (HIV-1) infection led to the hypothesis that gut reconditioning through probiotic administration could be protective for the gut surface and delay progression to Acquired Immunodeficiency Syndrome (AIDS) [1]
Emerging information clarifying the role of gut associated lymphoid tissue (GALT), altered microflora, and breakdown of the gut mucosal barrier in the etiology of HIV-1 disease have strengthened the rationale for use of probiotic bacteria in this setting
The recognition that changes in the normal bacterial flora have a profound impact on metabolism and inflammation has generated insight into potential mechanisms of gut dysfunction in HIV-1 infection

Summary

Introduction

The original perception that intestinal mucosal starvation could be a central cause of the mucosal atrophy, opportunistic bacterial growth, and microbial translocation in untreated HIV-1 infection led to the hypothesis that gut reconditioning through probiotic administration could be protective for the gut surface and delay progression to AIDS [1]. Probiotic bacteria promote normalization of flora in HIV-1 infected women with moderate bacterial vaginosis [23] Another recent study shows that dietary supplementation with a prebiotic oligosaccharide mixture improved the gut microbiota composition, reducing biomarkers of microbial translocation and T cell activation [24]. We present results from a small pilot study indicating that administration of probiotic bacteria to children with HIV-1 associated failure-to-thrive, had effects on growth as well as on peripheral immune blood immune response that support this concept Future studies in this area should be based on expanded methods of determining the presence and function of bacterial species by genetic and metagenomic approaches. The identification of the Th-17 pathway and the role of T regulatory cells provides a plausible mechanism of action and may be highly relevant for the potential exploration of probiotic bacteria in the setting of HIV disease in the future

Impact of Nutrient Status on HIV-1 Infection

Role of Microbial Translocation on Inflammation and HIV-1 Progression

Effect of HIV-1 and Probiotics on Microflora and Microbiota

Findings

Summary