Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

Carl J Fichtenbaum,David M Asmuth,John E Hinkle,Netanya Sandler Utay,Audrey L Shaw,Ma Somsouk,Bryon W Petschow,Eric M Weaver,Christopher J Detzel,Anoma Somasunderam

doi:10.20411/pai.v4i1.276

Abstract

Background:Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.Methods:In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.Results:One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).Conclusions:Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART.

Highlights

Human immunodeficiency virus (HIV) infection is characterized by profound depletion of CD4+ T cells systemically and in the gastrointestinal (GI) tract, compromised mucosal barrier function, translocation of microbial products, and chronic inflammation [1]
Circulating markers of intestinal permeability and IL-6 have been consistently predictive of non-AIDS events and mortality in people receiving suppressive antiretroviral therapy (ART) [2, 5]
We examined changes in CD4+ T-cell counts in the lowest quartile of CD4+ T-cell counts because people who have failed to normalize CD4+ T-cell counts may have the greatest potential to experience an immunologic benefit from attenuating systemic inflammation

Summary

Introduction

Human immunodeficiency virus (HIV) infection is characterized by profound depletion of CD4+ T cells systemically and in the gastrointestinal (GI) tract, compromised mucosal barrier function, translocation of microbial products, and chronic inflammation [1]. A key contributor to this chronic inflammation is increased translocation of microbial products across a permeable gut barrier from the intestinal lumen to the lamina propria and systemic circulation [1, 2]. These microbial products activate innate immune cells to produce pro-inflammatory cytokines, such as interleukin‐1β (IL‐1β), interleukin-6 (IL‐6), and tumor necrosis factor-a (TNF-α) [1]. Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease

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