Gastrointestinal Dysfunction and HIV Comorbidities

Sim, Jae-Il; Mukerji, Shibani S.; Russo, S.; Lo, Janet

doi:10.1007/s11904-020-00537-8

Cited by 30 publications

(19 citation statements)

References 45 publications

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“…ARV therapy has significantly improved the lifespan and quality of life for people living with HIV and yet, prolonged treatment is not without complication. Non-AIDS related co-morbidities are now a leading cause of mortality for people living with HIV and are attributed to inflammation 1 stemming, in part, from deficiencies in gastrointestinal immunity and epithelial integrity 49 . Microbiome-derived SCFAs such as butyrate are essential for the development and maintenance of gastrointestinal immunity and epithelial integrity 12 , 13 .…”

Section: Discussionmentioning

confidence: 99%

Butyrate administration is not sufficient to improve immune reconstitution in antiretroviral-treated SIV-infected macaques

Ortiz

Simpson

Langner

et al. 2022

Sci Rep

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Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity. Herein we assessed whether supplementation with the dietary supplement sodium butyrate would improve immune reconstitution and reduce inflammation in ARV-treated, simian immunodeficiency virus (SIV)-infected rhesus macaques. We demonstrate that butyrate supplementation does not significantly improve immune reconstitution, with no differences observed in systemic CD4+ T-cell frequencies, T-cell functionality or immune activation, microbial translocation, or transcriptional regulation. Our findings demonstrate that oral administration of sodium butyrate is insufficient to reduce persistent inflammation and microbial translocation in ARV-treated, SIV-infected macaques, suggesting that this therapeutic may not reduce co-morbidities and co-mortalities in treated people living with HIV.

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Section: Discussionmentioning

confidence: 99%

Butyrate administration is not sufficient to improve immune reconstitution in antiretroviral-treated SIV-infected macaques

Ortiz

Simpson

Langner

et al. 2022

Sci Rep

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“…However, ART does not comprehensively restore the compromised immune system, and a chronic state of inflammation persists in PLWH on ART, even after long-term viral suppression. This chronic inflammation is positively associated with non-AIDS comorbidities and premature aging (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV

et al. 2023

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The intestinal barrier has the daunting task of allowing nutrient absorption while limiting the entry of microbial products into the systemic circulation. HIV infection disrupts the intestinal barrier and increases intestinal permeability, leading to microbial product translocation. Convergent evidence has shown that gut damage and an enhanced level of microbial translocation contribute to the enhanced immune activation, the risk of non-AIDS comorbidity, and mortality in people living with HIV (PLWH). Gut biopsy procedures are invasive, and are not appropriate or feasible in large populations, even though they are the gold standard for intestinal barrier investigation. Thus, validated biomarkers that measure the degree of intestinal barrier damage and microbial translocation are needed in PLWH. Hematological biomarkers represent an objective indication of specific medical conditions and/or their severity, and should be able to be measured accurately and reproducibly via easily available and standardized blood tests. Several plasma biomarkers of intestinal damage, i.e., intestinal fatty acid-binding protein (I-FABP), zonulin, and regenerating islet-derived protein-3α (REG3α), and biomarkers of microbial translocation, such as lipopolysaccharide (LPS) and (1,3)-β-D-Glucan (BDG) have been used as markers of risk for developing non-AIDS comorbidities in cross sectional analyses and clinical trials, including those aiming at repair of gut damage. In this review, we critically discuss the value of different biomarkers for the estimation of gut permeability levels, paving the way towards developing validated diagnostic and therapeutic strategies to repair gut epithelial damage and to improve overall disease outcomes in PLWH.

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“…We are aware that this figure represents a global hypothesis derived from our results and that the implication of additional factors cannot be ruled out. In fact, it cannot be discarded that intestinal dysbiosis and enteropathy normally associated with chronic HIV infection [reviewed in (24)] could hinder intestinal iron absorption. Furthermore, defects in liver production, due to hepatic disorders, infection by hepatotropic viruses [highly prevalent in HIV-infected patients (25)] or hepatotoxicity (personal factors such as alcohol consumption, drugs, antibiotics, etc.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of iron metabolism modulators in virologically suppressed HIV-infected patients

Garrido-Rodríguez

Álvarez-Ríos²,

Olivas-Martínez³

et al. 2022

Front. Immunol.

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BackgroundIron metabolism plays an essential role in cellular functions. Since virologically suppressed chronic HIV-infected subjects under effective antiretroviral treatment (ART) exhibit a persistent immune dysfunction that leads to comorbidities, iron homeostasis may be relevant in this context. We aimed to explore iron metabolism in virologically suppressed chronic HIV infected subjects under a successful ART.MethodsIn this retrospective study, traditional iron metabolism biomarkers (total iron, ferritin, transferrin, and transferrin saturation index), as well as soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers were determined in virologically suppressed chronic HIV-infected subjects under at least 2 years of ART (HIV) who also had >350 CD4-T-cells/mm3 (N=92) from Spain. As controls, we collected non-HIV age-matched healthy donors (Young, N=25) and elderly subjects (>65 years old; Elderly; N=25). Additionally, an external group of non-HIV patients with ferritin<50 ng/mL diagnosed with absolute iron deficiency (Ferropenic group; N=84) was included. Comparisons between groups were performed using Kruskal-Wallis or Mann-Whitney U-tests, while associations between variables were explored by Spearman’s rho correlation coefficient.ResultsWe selected samples from HIV-infected subjects (aged 42[34-47], 95% males), young age-matched (aged 40[30-58], 60% males), and elderly controls (aged 82[78-88], 100% males). Compared to both healthy (Young and Elderly) groups, HIV exhibited decreased iron, transferrin saturation, and sTfR, and increased ferritin, but similar hepcidin levels. Notably, associations between sTfR and iron (Young, r=-0.587, p=0.002; Elderly, r=-0.496, p=0.012) or transferrin saturation index (Young, r=-0.581, p=0.002; Elderly, r=-0.489, p=0.013) were negative in both controls while positive in HIV (r=0.464, p<0.0001 and r=0.421, p<0.0001, respectively). Moreover, the expected negative correlation between hepcidin and sTfR, observed in controls (Young, r=-0.533, p=0.006; Elderly, r=-0.473, p=0.017), was absent in HIV (r=0.082; p=0.438). Interestingly, the HIV inflammatory profile differed from the Elderly one, who despite their inflammaging-related profile, succeed in maintaining these associations. Furthermore, subjects from the ferropenic group (aged 42[32-51], 5% males), showing significantly lower levels of hepcidin and higher sTfR, as expected, reflected similar correlations as those Young and Elderly, in contrast to HIV.ConclusionsVirologically suppressed chronic HIV-infected patients under successful ART exhibit altered levels of iron metabolism modulators suggesting a complex functional iron deficiency.

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Gastrointestinal Dysfunction and HIV Comorbidities

Cited by 30 publications

References 45 publications

Butyrate administration is not sufficient to improve immune reconstitution in antiretroviral-treated SIV-infected macaques

Butyrate administration is not sufficient to improve immune reconstitution in antiretroviral-treated SIV-infected macaques

Relevance of biomarkers indicating gut damage and microbial translocation in people living with HIV

Dysregulation of iron metabolism modulators in virologically suppressed HIV-infected patients

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