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

Abstract

Background: Increased 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. Methods: As 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. Results: Participants 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). Conclusions: Conversely 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 comorbidities. These insights are instrumental for orienting clinical investigations in PLWH.

Clinical characteristics and risk factors for poor prognosis among HIV patients with Talaromyces marneffei bloodstream infection

“…As mentioned previously, the BDG assay is helpful in the early detection of invasive fugal disease [ 31 , 32 ], including TM [ 33 ]. However, the elevation of BDG also have been linked to gut damage with increased intestinal permeability in HIV patients [ 34 , 35 ]. Furthermore, we found BDG was negatively correlated with the time required for blood culture turnaround in our analysis.…”

Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV

“…While our study failed to find an association between LPS and disease progression in our cohort of PLWHIV, it must be acknowledged that LPS measurement might not entirely capture the extent of MT, given its fluctuation during the day and its association with food intake and the fact that repeated measures of the markers post cART initiation were not available. A deeper understanding of the role of MT as cause of inflammation and disease progression in the course of cART could be gained by the comprehensive assessment of additional and reliable markers of both MT and inflammation, including the fungal translocation marker Beta d glucan (BDG) that has proven to maintaining stable plasma levels over 24 h, with stronger association with pro-inflammatory markers [ 47 – 49 ]. Also, a most comprehensive assessment of the interaction between several markers of microbial translocation and inflammation including IL-6 and D-dimer levels is strongly advocated to most finely unravel the possible mechanistic links between inflammation, MT and disease progression upon virally-suppressive cART.…”

Gut Leakage of Fungal‐Related Products: Turning Up the Heat for HIV Infection

“…In addition, we also demonstrated that BDG levels were stable throughout 24 hours in ART-treated PLWH, as opposed to LPS levels ( 44 ). Interestingly, LPS levels increased after lunch and dinner, and decreased during the night, while BDG levels were stable over 24 hours.…”