Weill-Cornell Cellular Immunology Laboratory, Division of Hematology/Oncology, Host Defenses Program, Department of Pediatrics, Weill Medical College of Cornell University, New York, NY 10065, USA.
Nutrients. 2011 Dec;3(12):1042-70. doi: 10.3390/nu3121042. Epub 2011 Dec 19.
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.
1995 年提出了益生菌给药可保护肠道表面,并可能延缓人类免疫缺陷病毒 1 型(HIV-1)感染向获得性免疫缺陷综合征(AIDS)进展的假说。在过去的五年中,新的研究阐明了 HIV-1 感染肠道相关淋巴组织(GALT)对随后微生物群的改变以及肠道粘膜屏障的破坏,导致发病机制和 AIDS 的发展的重要性。目前的研究表明,在 HIV-1 疾病早期,对正常微生物群起反应而分化的肠道 CD4+Th17 细胞会丢失。微生物易位和 T 调节(Treg)细胞反应的抑制与慢性免疫激活和炎症有关。上调 Treg 激活的益生菌组合已显示出在抑制包括炎症性肠病在内的自身免疫模型中的促炎免疫反应方面的希望,并为 HIV-1/AIDS 中使用益生菌提供了依据。在 HIV-1 感染早期,微生物组的紊乱导致潜在病原体的优势更大,双歧杆菌和乳杆菌的水平降低,粘膜炎症增加。慢性或反复感染和免疫激活的相互作用导致营养缺乏,尤其是在 HIV-1 感染的儿童中,这种营养缺乏具有持久的后果。虽然有效的抗逆转录病毒疗法(ART)提高了生存率,但消瘦仍然是生存的独立预测因素,也是主要的表现症状。先天性接触 HIV-1 是感染和未感染婴儿生长迟缓的危险因素。6 个月后进行营养干预似乎效果不大。对双歧杆菌乳杆菌补充婴儿配方的随机对照临床试验的荟萃分析表明,与单独使用配方相比,接受双歧杆菌乳杆菌的婴儿体重增加明显更大。初步研究表明,作为补充剂给予益生菌可改善生长并防止 CD4+T 细胞丢失。人们认识到正常细菌菌群可引发新生儿免疫反应,异常菌群对代谢有深远影响,这为包括 HIV-1 感染在内的许多情况下的肠道功能障碍的潜在机制提供了新的见解。如本文所述,目前和新兴的研究支持益生菌细菌可在 HIV-1 感染中提供特定益处的观点。益生菌细菌已被证明可有效治疗 HIV-1 阳性妇女的细菌性阴道病,并可促进先天性 HIV-1 感染婴儿的生长。益生菌细菌可能稳定 HIV-1 感染儿童的 CD4+T 细胞数量,并可能对胃肠道免疫系统的炎症和慢性免疫激活具有保护作用。