Markers of Microbial Translocation and Immune Activation Predict Cognitive Processing Speed in Heavy-Drinking Men Living with HIV.

Mollie Monnig,Bharat Ramratnam,Kenneth Mayer,Peter Monti,Christopher Kahler,Patricia Cioe,Ronald Cohen,David Pantalone

doi:10.3390/microorganisms5040064

Abstract

HIV infection and alcohol use disorder are associated with deficits in neurocognitive function. Emerging evidence points to pro-inflammatory perturbations of the gut-brain axis as potentially contributing to neurocognitive impairment in the context of HIV and chronic heavy alcohol use. This study examined whether plasma markers of microbial translocation (LPS) from the gastrointestinal tract and related immune activation (sCD14, EndoCAb) were associated with neurocognition in 21 men living with HIV who were virally suppressed on antiretroviral therapy. All participants met federal criteria for heavy drinking and were enrolled in a randomized controlled trial (RCT) of a brief alcohol intervention. This secondary analysis utilized blood samples and cognitive scores (learning, memory, executive function, verbal fluency, and processing speed) obtained at baseline and three-month follow-up of the RCT. In generalized estimating equation models, LPS, sCD14, and EndoCAb individually were significant predictors of processing speed. In a model with all biomarkers, higher LPS and sCD14 both remained significant predictors of lower processing speed. These preliminary findings suggest that inflammation stemming from HIV and/or alcohol could have negative effects on the gut-brain axis, manifested as diminished processing speed. Associations of microbial translocation and immune activation with processing speed in heavy-drinking PLWH warrant further investigation in larger-scale studies.

Highlights

40% of virally suppressed people living with HIV infection (PLWH) show some degree of cognitive impairment, the etiology of which is not fully understood at present [1]
We found that higher LPS, higher soluble cluster of differentiation 14 (sCD14), and lower EndoCab individually were associated with poorer processing speed, controlling for average weekly drinking and education
In heavy-drinking men living with HIV, higher levels of microbial translocation and associated immune activation predicted worse cognitive processing speed

Summary

Introduction

40% of virally suppressed people living with HIV infection (PLWH) show some degree of cognitive impairment, the etiology of which is not fully understood at present [1]. Independent of each other, HIV infection and heavy alcohol consumption have profoundly deleterious effects on the GI system Both HIV and heavy drinking are known to deplete gut lymphocytes, disrupt tight junction proteins, and perturb the composition of the gut microbiome in favor of more pathogenic bacteria [6,7,8,9,10,11,12,13]. A controlled alcohol administration experiment showed that a single binge-drinking episode caused microbial translocation and immune activation in healthy individuals [18] In clinical settings, these phenomena are observed in individuals with chronic alcohol use disorder [19,20,21,22]

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