Direct Biomarkers of Microbial Translocation Correlate with Immune Activation in Adult Zambians with Environmental Enteropathy and Hepatosplenic Schistosomiasis

Abstract

Abstract.Microbial translocation is a poorly understood consequence of several disorders such as environmental enteropathy (EE) and hepatosplenic schistosomiasis (HSS). Herein, we compared biomarkers of microbial origin and immune activation in adults with these disorders and in healthy controls. A cross-sectional study was conducted in participants with EE recruited from Misisi compound, Lusaka, Zambia; HSS patients and healthy controls from the University Teaching Hospital, Lusaka. Plasma lipopolysaccharides (LPSs) was measured by limulus amoebocyte lysate assay, plasma 16S ribosomal RNA (16S rRNA) gene copy number was quantified by quantitative real-time polymerase chain reaction, Toll-like receptor ligand (TLRL) activity by QUANTI-Blue detection medium, and cytokines from cell culture supernatant by Cytometric Bead Array. In univariate analysis LPS, 16S rRNA gene copy number, and TLR activity were all high and correlated with each other and with cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, and IL-4 secreted by the RAW-Blue cells. After controlling for baseline characteristic, biomarkers of microbial translocation in blood were predictors of TNF-α, IL-6, and IL-10 activation in cell culture supernatant from EE participants and HSS patients but not in healthy controls. TLR activity showed the strongest correlation with TNF-α. These data provide correlative evidence that microbial translocation contributes to systemic cytokine activation in two disorders common in the tropics, with total TLR ligand estimation showing the strongest correlation with TNF-α (r = 0.66, P < 0.001).

Healthcare Professionals’ Knowledge of Pharmacogenetics and Attitudes Towards Antimicrobial Utilization in Zambia: Implications for a Precision Medicine Approach to Reducing Antimicrobial Resistance

“…Additionally, contrary to previous studies ( Kaonga et al, 2017 ; Chabala et al, 2020 ), we found a male preponderance in this study (61.5%) probably due to the gender disparity that has been reported that women are less likely to participate in science and medicine ( Gayet-Ageron et al, 2019 ). In our study, at least two-thirds of HCPs believed individual variations can lead to different individual experiences with given medicines, similar to other studies ( Mahmutovic et al, 2018 ), which is important in the implementation of any PGx clinical care ( Muzoriana et al, 2017 ).…”

Adaptation of the small intestine to microbial enteropathogens in Zambian children with stunting

“…iFABP is an intracellular, mainly cytosolic protein of the enterocyte involved in long-chain fatty acid absorption 37 , which is released into the bloodstream by epithelial damage and is used as a biomarker of coeliac disease and environmental enteropathy 38 . LPS, a cell wall component of Gram-negative bacteria, is measured directly 39 using the Limulus amoebocyte lysate assay or indirectly using host-response molecules such as LBP and sCD14. These host molecules belong to the Toll-like receptor 4 complex on monocytes and macrophages, one of several LPS recognition systems 40 .…”

Pathophysiology of environmental enteric dysfunction and its impact on oral vaccine efficacy

“…MT can exacerbate chronic inflammatory states, 49 including EED. 50 Biomarkers of MT include: lipopolysaccharide (LPS), a component of bacterial cell walls; the soluble LPS co-receptor CD14 (sCD14), which is upregulated by LPS; and antibodies to the core LPS core antigen (EndoCAb), which decrease after LPS binding ( Table 2). Multiple other biomarkers are available that measure derangements in multiple domains of pathology, including permeability, enterocyte injury, and mucosal and systemic inflammation ( Table 2).…”