Chronic exposure to infectious agents results in environmental enteric dysfunction—a significant contributor to childhood stunting. Low plasma tryptophan (TRP), increased kynurenine (KYN), and KYN–TRP (KT) ratio are associated with infections and chronic immune activation. We postulated that both these conditions are interlinked, and therefore aimed to identify the association between KT ratio and the linear growth of Bangladeshi children. A total of 480 stunted and at risk of being stunted children aged 12–18 months were enrolled and provided nutrition intervention for 90 days. Plasma samples were assessed using liquid chromatography tandem mass spectrometry to measure TRP and KYN concentrations. Multivariable linear regression with generalized estimating equations was applied to analyze association between the KT ratio and linear growth. Tryptophan, KYN, and KT ratio were significantly higher in stunted children than in children at risk of being stunted both at baseline and at the end of nutrition intervention. Following intervention, the median (interquartile range [IQR]) KYN concentration was significantly reduced from 4.6 (3.6, 5.4) µmol/L to 3.9 (0.3, 7.6) µmol/L, and median (IQR) KT ratio decreased from 104 (80.9, 131) to 92.8 (6.6, 247) in stunted children. We also found KT ratio to be negatively associated (coefficient = −0.7; 95% CI = −1.13, −0.26; P-value = 0.002) with linear growth. In addition, KYN and KT ratio were positively correlated with fecal neopterin and plasma C-reactive protein, whereas TRP was negatively correlated with both of these biomarkers and alpha-1-acid glycoprotein. Our findings imply that KT ratio is associated in the pathophysiology of stunting as well as with biomarkers of inflammation in Bangladeshi children.

Infections and persistent immunological activation are linked to increased kynurenine (KYN) and the KYN-to-Tryptophan (TRP) or KT ratio and may be critical factors in undernutrition. We sought to determine the association between the KT ratio and adult malnutrition, as well as investigate if nutritional supplementation had any influence on the decrease of the KT ratio. A total of 525 undernourished adults aged 18–45 years were recruited and provided a nutrition intervention for 60 feeding days. TRP and KYN concentrations were determined from plasma samples using LC-MS/MS. At baseline, the median (interquartile range (IQR)) TRP, KYN and KT ratios were 24.1 (17.6, 34.3) µmol/L, 0.76 (0.53, 1.18) µmol/L and 30.9 (24.5, 41.7), respectively. Following intervention, the median (IQR) KYN and KT ratios were significantly reduced to 0.713 (0.46, 1.12) µmol/L and 27.5 (21.3, 35.8). The KT ratio was found to be inversely linked with adult BMI (coefficient: −0.09; 95% CI: −0.18, 0.004; p-value = 0.06) but not statistically significant. Additionally, Plasma CRP was correlated positively, while LRP1 was inversely correlated with the KT ratio. Our data suggest that in Bangladeshi adults, the KT ratio is not related to the pathophysiology of malnutrition but correlated with inflammatory and anti-inflammatory biomarkers, and the ratio can be reduced by a nutrition intervention.

Environmental enteric dysfunction (EED) is a subacute syndrome characterized by increased intestinal inflammation and permeability that affects children in low-income countries. It is associated with growth and neurodevelopmental deficits, and there is currently no known treatment for EED. VS001 (AmiLyfe Bioscience, LLC, Norwood, MA) is a medical food (beverage) containing free amino acids that has been shown to decrease enteric inflammation and improve gut permeability in murine models. We conducted a double-blind, placebo-controlled pilot study to assess the acceptability and tolerability of VS001 in Bangladeshi children aged 1–2 years (n = 10 per arm). We also examined the effects on EED biomarkers (lactulose–mannitol (LM) ratio, fecal lactoferrin, alpha-antitrypsin, myeloperoxidase, and neopterin). Participants received 8 oz. of VS001 or an identical vehicle without amino acids daily for 14 days. Tolerability and acceptability were measured using parental surveys and daily in-home adverse event monitoring. Subjects took an average of 118 minutes to complete the dose each day. Caregivers found the product convenient and easy to administer and either agreed or strongly agreed that they would give this product to their child again. None reported that the intervention negatively affected their child’s appetite. There were three mild adverse events deemed possibly related to the intervention, with two occurring in the active arm and one in the control arm. Children in the active arm exhibited a nonsignificant decrease in LM ratios (a marker of intestinal permeability) after treatment compared with the control arm (0.19–0.08 versus 0.19–0.17; P = 0.16). VS001 was acceptable to parents and reasonably well tolerated. Given the decrease in permeability observed in the active arm, a larger trial is warranted.