Changes in the Fungal Marker β-D-Glucan After Antiretroviral Therapy and Association With Adiposity

Dirajlal-Fargo, Sahera; Moser, Carlee; Rodríguez, Katherine; Kamari, Vanessa El; Funderburg, Nicholas; Bowman, Emily; Brown, Todd T.; Hunt, Peter W.; Currier, Judith S.; McComsey, Grace A.

doi:10.1093/ofid/ofz434

Cited by 18 publications

(24 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11,26,[32][33][34][35][36] In the setting of HIV, higher blood BDG levels are associated with increased fat gain in ART-naïve PWH initiating treatment and with immune activation, increased systemic inflammation in ART-treated PWH and non-AIDS clinical events. 5, [16][17][18][19][20]37,38 Thus, there is a need to determine when best to measure markers of microbial translocation and gut damage in order to deliver accurate diagnostics and to assess treatment responses.…”

Section: Discussionmentioning

confidence: 99%

“…Certain contributors that give rise to fungal translocation include medical procedures such as surgery and haemodialysis, as well as conditions like liver cirrhosis, immune dysfunction, sepsis, intestinal hypoperfusion and persistent inflammation 11,26,32‐36 . In the setting of HIV, higher blood BDG levels are associated with increased fat gain in ART‐naïve PWH initiating treatment and with immune activation, increased systemic inflammation in ART‐treated PWH and non‐AIDS clinical events 5,16‐20,37,38 . Thus, there is a need to determine when best to measure markers of microbial translocation and gut damage in order to deliver accurate diagnostics and to assess treatment responses.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Glucan rich nutrition does not increase gut translocation of beta‐glucan

Hoenigl

Lin

Finkelman³

et al. 2020

Mycoses

View full text Add to dashboard Cite

Background: (1-3)-b-D-glucan (BDG) is a fungal cell wall component and, in the absence of invasive fungal infection, a novel biomarker for microbial translocation of endogenous fungal products from the gastrointestinal tract into systemic circulation. However, its value as a marker of fungal translocation is limited by a concern that plant BDG-rich food influences blood BDG levels. Methods: We conducted a pilot clinical trial to evaluate the impact of a standardised oral BDG challenge on blood BDG levels in participants with and without elevated microbial translocation. We enrolled 14 participants including 8 with HIV infection, 2 with advanced liver cirrhosis, and 4 healthy controls. After obtaining a baseline blood sample, participants received a standardised milkshake containing high levels of BDG followed by serial blood samples up to 8 hours after intake. Results: The standardised oral BDG challenge approach did not change the blood BDG levels over time in all participants. We found consistently elevated blood BDG levels in one participant with advanced liver cirrhosis and a single person with HIV with a low CD4 count of 201 cells/mm 3. Conclusion: Our findings indicate that BDG blood levels were not influenced by plant origin BDG-rich nutrition in PWH, people with advanced liver cirrhosis, or healthy controls. Future studies are needed to analyse gut mycobiota populations in individuals with elevated blood BDG levels.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Glucan rich nutrition does not increase gut translocation of beta‐glucan

Hoenigl

Lin

Finkelman³

et al. 2020

Mycoses

View full text Add to dashboard Cite

show abstract

“…Circulating BDG is currently used for the clinical diagnosis of Candida, Aspergillus, and Pneumocystis jirovecii invasive infections [33]. Recently, 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]. We have also shown that plasma BDG levels are associated with reduced expression of Dectin-1 and NKp30 on monocytes and NK cells respectively, indicating direct cellular activation and inflammation by BDG.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

View full text Add to dashboard Cite

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.

show abstract

“…first showed elevated plasma levels of BDG in PLWH in 2012 ( 19 ). Since then, several other groups including ours reported an association between BDG and epithelial gut damage, immune activation, inflammation, and risk of developing non-AIDS comorbidities ( 4 , 15 , 20 – 24 ). These findings suggest a significant role for BDG in chronic immune activation and the development of non-AIDS comorbidities in PLWH, although the mechanisms involved remain poorly understood.…”

Section: Introductionmentioning

confidence: 73%

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

Isnard

Lin

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

The intestinal epithelial layer serves as a physical and functional barrier between the microbiota in the lumen and immunologically active submucosa. Th17 T-cell function protects the gut epithelium from aggression from microbes and their by-products. Loss of barrier function has been associated with enhanced translocation of microbial products which act as endotoxins, leading to local and systemic immune activation. Whereas the inflammatory role of LPS produced by Gram-negative bacteria has been extensively studied, the role of fungal products such as β-D-glucan remains only partially understood. As HIV infection is characterized by impaired gut Th17 function and increased gut permeability, we critically review mechanisms of immune activation related to fungal translocation in this viral infection. Additionally, we discuss markers of fungal translocation for diagnosis and monitoring of experimental treatment responses. Targeting gut barrier dysfunction and reducing fungal translocation are emerging strategies for the prevention and treatment of HIV-associated inflammation and may prove useful in other inflammatory chronic diseases.

show abstract

Changes in the Fungal Marker β-D-Glucan After Antiretroviral Therapy and Association With Adiposity

Cited by 18 publications

References 39 publications

Glucan rich nutrition does not increase gut translocation of beta‐glucan

Glucan rich nutrition does not increase gut translocation of beta‐glucan

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

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

Contact Info

Product

Resources

About