Association of Intestinal Amino Acid Absorption with the Uptake of Lactulose and Rhamnose in Adults with Environmental Enteropathy

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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.

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