Bacterial Translocation and Host Immune Activation in Chronic Hepatitis C Infection

Moon, Mi Sun; Quinn, Gabriella; Townsend, Elizabeth; Ali, Rabab; Zhang, Grace Y; Bradshaw, Alyson; Hill, Kareen; Guan, Hannah; Hamilton, Destanee; Kleiner, David E.; Koh, Christopher; Heller, Theo

doi:10.1093/ofid/ofz255

Cited by 13 publications

(19 citation statements)

References 17 publications

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“…31 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][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%

“…Furthermore, damage to the physiological barrier of the gut allows translocation of fungal products from the intestinal lumen into the blood 31 . 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 .…”

Section: Discussionmentioning

confidence: 99%

“…Exclusions were invasive fungal infection, haemodialysis with cellulose‐containing membranes, diabetes mellitus or low blood sugar, history of high/low blood pressure, intake of nutritional supplements containing high doses of BDG within 24 hours of the study visit and use of antibiotics or anticholinergic drugs within the last 14 days. Of these, (a) four were PWH with CD4 T‐cell count < 350 cells/mm 3 and/or on antiretroviral therapy (ART) for less than eight weeks with viral load (VL) > 1000 copies/mL, (b) four were PWH on ART with suppressed VL and with CD4 + T‐cell count > 350 cells/mm 3 , (c) two were participants without HIV but with hepatitis‐C (HCV)‐associated liver cirrhosis Child‐Pugh class B or C, 26 and (d) four were controls without HIV and HCV.…”

Section: Methodsmentioning

confidence: 99%

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

Hoenigl

Lin

Finkelman³

et al. 2020

Mycoses

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Hoenigl

Lin

Finkelman³

et al. 2020

Mycoses

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“…The peripheral BDG titers in the infected patients were significantly higher than the uninfected patient levels, suggesting the potential of diagnostic utility despite compromised clearance. Recently, Moon et al 2020 analyzed microbial translocation markers in the blood of hepatitis C virus infected patients [ 85 ]. Serum BDG was significantly elevated in hepatic fibrosis (Ishak Score 0–2 and 5–6), relative to controls (Mann–Whitney, p < 0.0001 and p < 0.001, respectively).…”

Section: Major Sources Of Circulating Bdgmentioning

confidence: 99%

Specificity Influences in (1→3)-β-d-Glucan-Supported Diagnosis of Invasive Fungal Disease

Finkelman

2020

JoF

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(1→3)-β-glucan (BDG) testing as an adjunct in the diagnosis of invasive fungal disease (IFD) has been in use for nearly three decades. While BDG has a very high negative predictive value in this setting, diagnostic false positives may occur, limiting specificity and positive predictive value. Although results may be diagnostically false positive, they are analytically correct, due to the presence of BDG in the circulation. This review surveys the non-IFD causes of elevated circulating BDG. These are in the main, iatrogenic patient contamination through the use of BDG-containing medical devices and parenterally-delivered materials as well as translocation of intestinal luminal BDG due to mucosal barrier injury. Additionally, infection with Nocardia sp. may also contribute to elevated circulating BDG. Knowledge of the factors which may contribute to such non-IFD-related test results can improve the planning and interpretation of BDG assays and permit investigational strategies, such as serial sampling and BDG clearance evaluation, to assess the likelihood of contamination and improve patient care.

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“…designed a clinical trial where people were fed with high-BDG food in a controlled environment ( 41 ). This study included participants with advanced HCV-associated liver cirrhosis as positive controls, as those patients have elevated microbial translocation levels ( 46 – 49 ). Other included participants constituted of PLWH with detectable viral loads, ART-suppressed PLWH, and HCV negative/HIV negative controls.…”

Section: Validating Bdg As a Marker Of Microbial Translocation In Plwhmentioning

confidence: 99%

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

Isnard

Lin

et al. 2021

Front. Immunol.

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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.

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Bacterial Translocation and Host Immune Activation in Chronic Hepatitis C Infection

Cited by 13 publications

References 17 publications

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

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

Specificity Influences in (1→3)-β-d-Glucan-Supported Diagnosis of Invasive Fungal Disease

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

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