Daily variations of gut microbial translocation markers in ART-treated HIV-infected people

Jing Ouyang,John Lin,Malcolm Finkelman,Etiene Moreira Gabriel,Brandon Fombuena,Delphine Planas,Daniel E Kaufmann,Yaokai Chen,Stéphane Isnard,Yonglong Zhang,Tomas Raul Wiche Salinas,Debashree Chatterjee,Amélie Cattin,Nicolas Cermakian,Jean-Pierre Routy,Augustine Fert,Laurence Raymond Marchand,Petronela Ancuta

doi:10.1186/s12981-020-00273-4

Abstract

BackgroundIncreased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). Evidence in animal models have shown that markers of intestinal permeability and microbial translocation vary over the course of the day and are affected by food intake and circadian rhythms. However, daily variations of these markers are not characterized yet in PLWH. Herein, we assessed the variation of these markers over 24 h in PLWH receiving antiretroviral therapy (ART) in a well-controlled environment.MethodsAs in Canada, PLWH are predominantly men and the majority of them are now over 50 years old, we selected 11 men over 50 receiving ART with undetectable viremia for more than 3 years in this pilot study. Blood samples were collected every 4 h over 24 h before snacks/meals from 8:00 in the morning to 8:00 the next day. All participants consumed similar meals at set times, and had a comparable amount of sleep, physical exercise and light exposure. Plasma levels of bacterial lipopolysaccharide (LPS) and fungal (1→3)-β-D-Glucan (BDG) translocation markers, along with markers of intestinal damage fatty acid binding protein (I-FABP) and regenerating islet-derived protein-3α (REG3α) were assessed by ELISA or the fungitell assay.ResultsParticipants had a median age of 57 years old (range 50 to 63). Plasma levels of BDG and REG3α did not vary significantly over the course of the study. In contrast, a significant increase of LPS was detected between 12:00 and 16:00 (Z-score: − 1.15 ± 0.18 vs 0.16 ± 0.15, p = 0.02), and between 12:00 and 24:00 (− 1.15 ± 0.18 vs 0.89 ± 0.26, p < 0.001). The plasma levels of I-FABP at 16:00 (− 0.92 ± 0.09) were also significantly lower, compared to 8:00 the first day (0.48 ± 0.26, p = 0.002), 4:00 (0.73 ± 0.27, p < 0.001) or 8:00 on secondary day (0.88 ± 0.27, p < 0.001).ConclusionsConversely to the fungal translocation marker BDG and the gut damage marker REG3α, time of blood collection matters for the proper evaluation for LPS and I-FABP as markers for the risk of inflammatory non-AIDS co-morbidities. These insights are instrumental for orienting clinical investigations in PLWH.

Highlights

Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH)
In contrast to the global health improvement occurring in people living with HIV (PLWH) receiving antiretroviral therapy (ART), gut damage persists and translocation of microbial products from the gut lumen into the circulation contributes to inflammatory non-AIDS comorbidities [5]
Plasma viral load (VL) of all participants were below the level of detection (< 20 copies/ml)

Summary

Introduction

Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). In contrast to the global health improvement occurring in people living with HIV (PLWH) receiving antiretroviral therapy (ART), gut damage persists and translocation of microbial products from the gut lumen into the circulation contributes to inflammatory non-AIDS comorbidities [5]. We and others have found that plasma levels of BDG are associated with epithelial gut damage and risk of developing inflammatory non-AIDS comorbidities in PLWH without invasive fungal infection (IFI) [24, 25, 28, 29, 33,34,35,36]. Assessment of BDG levels may be useful in predicting the risk of PLWH to develop non-AIDS comorbidities [24,25,26]

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Results

Conclusion