Microbial Translocation and Metabolic and Body Composition Measures in Treated and Untreated HIV Infection

Abstract

Circulating levels of microbial products such as lipopolysaccharide (LPS) are increased in HIV infection. Microbial translocation promotes obesity, insulin resistance, and dyslipidemia in other settings. We examined data from 178 subjects: an Indiana University (IU) cross-sectional study [N = 49 on antiretroviral therapy (ART), N = 47 not on ART], and a 24 week prospective study of ART initiation ACTG 5152s (N = 82). Pearson correlations were used to describe relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte activation, with metabolic and body composition measures. HOMA-IR (a measure of insulin resistance) and LPS were correlated for the combined cohorts (r = 0.19, p = 0.02), particularly in the 5152s ART-naive cohort (r = 0.41, p < 0.01). Triglycerides were correlated with LPS in the combined cohort (r = 0.32, p < 0.01), and all subsets excluding the IU on ART subset. There were negative correlations between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r = -0.21, p < 0.01), as well as the IU subset not on ART (r = -0.32, p = 0.04). Large particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was negatively correlated with LPS (r = -0.18, p = 0.02), particularly among the IU subset receiving ART (r = -0.33, p = 0.03). In the combined cohorts, sCD14 was negatively correlated with lean mass as well as trunk and limb fat. There is a relationship between microbial translocation markers and metabolic effects, particularly lipoproteins. During prolonged ART, microbial translocation was associated with an adverse effect on large HDL and thus may contribute to the increased cardiovascular disease risk observed during chronic treatment of HIV.

Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

“…91 These findings are well in line with recent reports of strong correlations between LPS and both elevated fasting triglycerides and low HDL cholesterol, 92 as well as low levels of large particle HDL cholesterol. 93 Several mechanisms could explain these associations. First, LPS and triglycerides are cotransported in chylomicrons from the gut to circulation 94 where LPS is scavenged by HDL cholesterol, which is often low in dyslipidemia.…”

Does systemic inflammation and immune activation contribute to fracture risk in HIV?

“…Furthermore, injection of LPS into T- and B-cell deficient mice can induce significant bone loss [55]. Whilst higher circulating levels of LPS and monocyte activation markers such as sCD14 and sCD163 have been reported in HIV-infected patients [38, 39, 41, 56, 57], their impact on bone loss remains to be fully determined.…”

“…The resulting imbalance in the RANKL:OPG ratio therefore potentially contributing to the greater BMD loss seen in the standard group. The ACTG study A5303, which examined BMD changes in 259 ART naïve patients commencing therapy, comparing maraviroc with TDF [57] recently completed work on the immunology substudy and did not detect any significant associations between changes in immunological markers (measured at baseline and week 48) and percent change in hip BMD. The completed results of this study are to be presented at the 2016 Conference on Retroviruses and Opportunistic Infections in Boston, MA.…”

Overweight/Obesity and HIV Disease Progression in HIV+ Adults in Botswana

“…Timmons et al 47 did not show significant association between LPS and body composition; however, they did report relationship with sCD14. Soluble CD14 is a measure of microbial translocation, which is freed from monocytes by LPS stimulation.…”

“…45,46 The gene was originally found in mice and was responsible for the fused toe (Ft) phenotype and also provided the gene its name. 47 The hypothalamus is the site where the FTO gene is mainly expressed 48 and may be involved in energy homeostasis, 49 and fat cell lipolysis which may regulate body fat. 50 Specifically, the single nucleotide polymorphism (SNP) of the FTO gene rs9939609 A allele is most commonly associated with obesity.…”