Helminth Mediated Attenuation of Systemic Inflammation and Microbial Translocation in Helminth-Diabetes Comorbidity

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by heightened systemic inflammation and microbial translocation. Whether concomitant helminth infections can modulate this systemic response is unclear. We examined the presence of markers of systemic inflammation (levels of acute phase proteins) and of microbial translocation [levels of lipopolysaccharide (LPS) and its associated products] in T2DM individuals with (Ss⁺) or without (Ss^-) Strongyloides stercoralis (Ss) infection. We also analyzed these parameters at 6 months following anthelmintic treatment in Ss⁺ individuals. Ss⁺ individuals exhibited significantly diminished levels of alpha-2 macroglobulin, C-reactive protein, haptoglobin and serum amyloid protein A1 compared to Ss^- individuals and these levels increased significantly following therapy. Similarly, Ss⁺ individuals exhibited significantly diminished levels of LPS, sCD14, intestinal fatty acid binding protein, LPS binding protein and endotoxin IgG antibody and most of these levels increased significantly following therapy. Thus, helminth infection is associated with attenuation of systemic inflammation and microbial translocation in T2DM and its reversal following anthelmintic therapy.

Keywords: acute phase proteins; helminths; microbial translocation; systemic inflammation; type 2 diabetes mellitus.

Figure 1

Diminished systemic levels of acute phase proteins in helminth-diabetes comorbidity and partial reversal after anthelmintic treatment. (A) Plasma levels of a-2 Macroglobulin, C-reactive protein (CRP), haptoglobin, and Serum Amyloid A-1 (SAA-1) from Ss infected [Ss⁺] (n = 60) or uninfected [Ss⁻] (n = 58) individuals were measured by multiplex assay. Data are shown as scatter plots with the bar representing the geometric mean. p-values were calculated using the Mann-Whitney U-test with Holms correction for multiple comparisons. (B) Plasma levels of a-2 Macroglobulin, C-reactive protein (CRP), haptoglobin, and serum amyloid proteins (SAA), from Ss-infected individuals at pre-treatment [pre-T] (n = 60) and at 6 months following treatment [post-treatment (post-T)] were measured by multiplex assay. The arrow shows the directionality of the significance. p-values were calculated using the Wilcoxon matched pair test.

Figure 2

Diminished systemic levels of microbial translocation markers in helminth-diabetes comorbidity and partial reversal after anthelmintic treatment. (A) Plasma levels of lipopolysaccharide (LPS), soluble CD14 (sCD14), intestinal fatty acid binding protein (iFABP), lipid binding protein (LBP), and endotoxin core antibody IgG (EndoCAb), from Ss infected [Ss⁺] (n = 60) or uninfected [Ss⁻] (n = 58) individuals were measured by ELISA. Data are shown as scatter plots with the bar representing the geometric mean. p-values were calculated using the Mann-Whitney U-test with Holms correction for multiple comparisons. (B) Plasma levels of lipopolysaccharide (LPS), soluble CD14 (sCD14), intestinal fatty acid binding protein (iFABP), lipid binding protein (LBP), and endotoxin core antibody IgG (EndoCAb) from Ss-infected individuals at pre-treatment [pre-T] (n = 60) and at 6 months following treatment [post-treatment (post-T)] were measured by ELISA. The arrow shows the directionality of the significance. p-values were calculated using the Wilcoxon matched pair test.