Association of Intestinal Amino Acid Absorption with the Uptake of Lactulose and Rhamnose in Adults with Environmental Enteropathy.
It is not clear whether impaired amino acid (AA) absorption occurs in adults with environmental enteropathy (EE). Therefore, we set out to determine the association between intestinal 13C615N-allo-isoleucine absorption (reflecting neutral AA transport) and lactulose-rhamnose ratio (LRR, reflecting permeability) in healthy adult volunteers (aged 18-35 years; N = 6) from India, and in those with biopsy-confirmed EE (N = 20) from Zambia. A 3-hour oral bolus protocol using 13C615N-allo-isoleucine (M), co-administered with lactulose and rhamnose sugars, was used to estimate AA absorption (as M area under the curve [AUC]) and LRR. Additionally, duodenal biopsies were collected from participants in Zambia. There was no association between allo-isoleucine absorption and LRR (separately by site or combined), but there was a significant positive correlation with crypt depth (N = 16; Spearman's rank correlation coefficient [rs] = 0.666; P-value = 0.005) in the Zambian participants. However, on exploratory analysis, the peak concentration (within first hour post-dose) of allo-isoleucine was significantly and positively correlated with the percentage of rhamnose dose recovered (%R; N = 24, participants combined; rs = 0.434; P-value = 0.034), and with crypt depth (N = 16; rs = 0.713; P-value = 0.002). There were differences noted between the two sites: Zambian participants had a significantly lower median [range]%R (3.0 [1.0-4.6] versus 6.1% [3.2-7.7]) and allo-isoleucine (M + [M-1] AUC, 1.62 [0.73-5.44] versus 4.41 [3.69-5.37] µM*h/L) compared with those from India. In conclusion, allo-isoleucine absorption correlated with %R (reflecting intestinal absorptive surface area) but not LRR.