Table 2.
Biomarkers of microbial translocation and mucosal dysfunction in environmental, HIV and malnutrition enteropathy.
| Biomarker | Normal rangea | HIV negative children with SAM (n = 20) |
HIV positive children with SAM (n = 14) | HIV negative adults (n = 39) | HIV positive adults (n = 22) | Community children (n = 101) | P |
|---|---|---|---|---|---|---|---|
| 16S rDNA PCR positive | Not established | 8/14 (57%) | 4/6 (67%) | 19/34 (56%) | 14/20 (70%) | 13/82 (16%) | < 0.0001 |
| LPS (EU/ml) | Not established | 272 (142–600) [0–2097] n = 15 |
120 (0 − 223) [0–339] n = 7 |
187 (92–374) [23–1219] n = 36 |
122 (66–202) [36–536] n = 22 |
50.9 (0 − 111) [0–869] n = 108 |
0.0001 |
| LBP (ng/ml) | Not established | 150 (148–190) [135–258] n = 15 |
253 (170–356) [159–530] n = 7 | 22.9 (19.8,28.5) [15.1–35.9] n = 39 |
28.9 (26.6,37.2) [15.5 = 43.1] n = 22 |
40.3 (32.9–48.2) [1.8–82.8] n = 94 |
0.0001 |
| sCD14 (mg/l) | 0.8–3.2 | 2.53 (2.19–3.31) [1.10–4.51] n = 16 |
2.84 (1.50–3.72) [1.04–5.49] n = 7 |
1.62 (1.34–1.84) [0.74–2.46] n = 39 |
1.84 (1.40–2.41) [0.54–4.24] n = 22 |
1.78 (1.54–2.14) [0.80–3.37] n = 78 |
0.0001 |
| CD163 (μg/l) | 88–902 | 1226 (1007–1983) [425–3860] n = 16 |
1482 (661–3147) [551–3441] n = 7 |
618 (408–804) [188–1706] n = 39 |
684 (453–1068) [50–2605] n = 22 |
874 (686–1305) [318–2331] n = 78 |
0.0001 |
| CRP (mg/l) | 0–5.0 | 1.75 (0.63–5.09) [0.05–21.0] n = 16 |
3.67 (0.50–10.31) [0.46–21.0] n = 7 | 0.95 (0.47–2.45) [0–16.4] n = 39 |
2.31 (0.64–10.3) [0.14–21.0] n = 22 |
nt | ns |
| FABP (ng/ml) | Not established | 3.14 (2.5–4.8) [0.38–13.5] n = 19 |
4.52 (2.76–13.47) [2.66–15.8] n = 7 | 0.65 (0.44–0.86) [0.18–3.2] n = 39 |
0.64 (0.49–1.4) [0–3.43] n = 22 |
2.01 (1.33,3.04) [0.17–13.2] n = 74 |
0.0001 |
| GLP-2 (ng/ml) | Median 11.6, IQR 7.0–18.6 |
1.8 (1.0–2.3) [0.5–5.1] n = 14 |
4.1 (2.2–5.6) [0.4–7.6] n = 7 |
1.2 (0.8–2.1) [0–5.4] n = 39 |
1.0 (0–2.0) [0–5.3] n = 22 |
2.0 (1.5–2.7) [0–5.4] n = 75 |
0.0007 |
| IGF-1 (ng/ml) | 43–182 | 11.7 (9.8–20.2) [9.3–39.4] n = 15 |
9.3 (9.3–10.1) [9.3–12.7] n = 6 |
nt | nt | 26.1 (19.4–36.4) [0–143] n = 79 |
0.0001 |
| IGFBP-3 (μg/ml) | 1.53–3.09 | 0.89 (0.35–1.67) [0.23–2.25] n = 15 |
0.70 (0.49–0.89) [0–1.34] n = 6 |
nt | nt | 1.22 (0.93–1.43) [0.34–2.53] n = 76 |
0.02 |
| Lactulose recovery (% of administered dose) | Children: median 0.01 (range 0–0.07) Adults: mean 0.281 (sd 0.014) |
0.0287 (0.017–0.083) [0.002–0.18] n = 8 |
0.10 (0.017–0.474) [0.015–0.78] n = 4 |
0.0823 (0.049–0.120) [0.0147–0.413] n = 38 |
0.0597 (0.04–0.137) [0.0009–0.25] n = 22 |
0.009 (0.002–0.026) [0–0.299] n = 76 |
0.0001 |
| Rhamnose recovery (% of dose) | Children: median 0.38 (range 0–1.84) Adults: mean 11.1 (sd 0.4) |
0.087 (0.072–0.273) [0.03–1.16] n = 8 |
0.15 (0.068–0.46) [0.03–0.72] n = 4 |
1.70 (0.877–2.62) [0.3–5.66] n = 38 |
1.21 (0.42–1.85) [0.3.51] n = 22 |
0.17 (0.03–0.42) [0.007–1.75] n = 76 |
0.0001 |
| L:R recovery ratio | Children: median 0.14 (range 0.06–1.00) Adults: mean 0.026 (sd 0.0001) |
0.213 (0.129–0.289) [0.062–1.070] n = 8 |
0.762 (0.357–1.00) [0.148–1.05] n = 4 |
0.055 (0.045–0.072) [0.014–0.180] n = 38 |
0.066 (0.039–0.103) [0.030–0.50] n = 20 |
0.071 (0.037–0.12) [0–1.289] n = 76 |
0.0001 |
| Anti-TTG IgA (Inova) (U/ml) | Below 10 | 0.54 (0.51–0.59) [0.48–0.72] n = 16 |
0.61 (0.56–1.09) [0.54–1.99] n = 7 |
0.57 (0.54–0.64) [0.05–3.66] |
0.60 (0.55–0.63) [0.52–0.84] |
nt | 0.02 |
| Anti-TTG IgA (Orgentech) (U/ml) | Below 10 | 2.12 (2.02–2.21) [1.93–2.84] n = 16 |
2.44 (2.30–2.68) [2.22–2.87] n = 4 |
2.30 (2.18–2.46) [2.10–6.15] |
2.23 (2.18–2.36) [2.06–2.71] |
0 (0–0) 0–2.81] |
0.0001 |
| Anti-DGP IgG (U/ml) | Below 30 | 1.6 (1.4–3.6) [1.1–12.3] n = 16 |
15.7 (4.0–45.7) [2.4–102.2] n = 7 |
1.48 (1.41–2.04) [1.20–4.60] |
1.51 (1.42–1.96) [1.20–6.58] |
nt | 0.0007 |
P is the result of Kruskal-Wallis test or Fisher's exact test across all groups. n is shown where it is less than the number of participants shown at the head of the column. nt, not tested; ns, not significant. LPS, lipopolysaccharide; LBP, LPS binding protein; sCD14, soluble cluster of differentiation 14; CD163, cluster of differentiation 163; CRP, C-reactive protein; FABP, fatty acid binding protein; GLP-2, glucagon-like peptide 2; IGF-1, insulin-like growth factor-1; IGFBP-3, IGF binding protein-3; TTG, tissue transglutaminase; DGP, deamidated gliadin peptides.
Reference ranges are obtained from package inserts in ELISA kits, except for: mono- and disaccharide excretion in children (Faubion et al., 2016), mono- and disaccharide excretion in adults (Menzies et al., 1999); GLP-2 (Hoffmann, 2009); normal values for some molecules are not established. In the study by Menzies et al. (1999) a 5-hour collection was used so recoveries would be expected to be higher; the LR ratio remains unchanged over 3 or 5 h.