HIV Molecular Research Group, School of Medicine, University College Dublin, Catherine McAuley Centre for Education and Research.
Mater Misericordiae University Hospital, Dublin, Ireland.
Curr Opin HIV AIDS. 2018 Jan;13(1):28-37. doi: 10.1097/COH.0000000000000425.
The role of the gut microbiome in the pathogenesis of several inflammatory, non-AIDS comorbidities, such as cardiovascular disease, cognitive impairment and liver disease has become a focus of recent research. Low bone mineral density (BMD) and increased fracture incidence in people living with HIV (PLWH) is also widely reported, however, the relationship between alterations in the gut microbiome and bone disease in PLWH has not been previously reviewed.
Murine models that manipulate the gut microbiome, either through breeding of 'germ-free' mice or antibiotic-depleted gut microbiome, show differences in bone mineral density and bone mass in those with altered gut microbiome. This effect is reported to be driven via changes in the gut-immune-skeletal axis, with changes favouring bone resorption. Several inflammatory conditions wherever bone loss is a prominent feature, such as rheumatoid arthritis and inflammatory bowel disease, have also reported alterations in the gut microbiome, which are associated with bone loss, again through changes in the gut-immune-skeletal axis.
The interplay between the gut microbiome and the immune-skeletal axis in HIV represents a complex relationship. Alterations in the gut microbiome, which induce an activated immune phenotype and inflammatory milieu are associated with non-AIDS comorbidities in PLWH and bone loss in several other conditions characterized by chronic immune activation and inflammation. It is, therefore, likely that there are comparable effects between altered gut microbiome and bone loss in HIV, however, further research is required to better define this relationship in populations of PLWH.
肠道微生物组在几种非艾滋病炎症性合并症（如心血管疾病、认知障碍和肝病）的发病机制中的作用已成为近期研究的焦点。艾滋病毒感染者（PLWH）中普遍存在低骨密度（BMD）和骨折发生率增加的情况，但肠道微生物组的改变与 PLWH 骨骼疾病之间的关系尚未得到系统回顾。
通过无菌小鼠或抗生素耗尽的肠道微生物组来操纵肠道微生物组的小鼠模型表明，肠道微生物组改变的小鼠的骨矿物质密度和骨量存在差异。这种影响被认为是通过肠道-免疫-骨骼轴的变化来驱动的，这些变化有利于骨吸收。几种炎症性疾病，如类风湿关节炎和炎症性肠病，也报告了肠道微生物组的改变，这些改变与骨丢失有关，同样是通过肠道-免疫-骨骼轴的变化。
肠道微生物组与 HIV 中的免疫骨骼轴之间的相互作用代表了一种复杂的关系。肠道微生物组的改变，诱导激活的免疫表型和炎症环境，与 PLWH 的非艾滋病合并症以及其他几种以慢性免疫激活和炎症为特征的疾病的骨丢失有关。因此，肠道微生物组的改变与 HIV 中的骨丢失之间可能存在类似的影响，但需要进一步的研究来更好地定义 PLWH 人群中的这种关系。
