Assessment of tryptophan metabolism and signs of depression in individuals with carbohydrate malabsorption
Introduction
Carbohydrate malabsorption is a frequent and widespread gastrointestinal condition (Born, 2007). The disaccharide lactose and the monosaccharide fructose are important carbohydrates, which are included in the daily human diet all over the world (Born, 2007, Ladas et al., 2000).
Primary adult-type lactose malabsorption is an inherited autosomal recessive condition with declined lactase activity in the small intestine (Usai-Satta et al., 2012). The incomplete hydrolysis of the non-absorbable disaccharide lactose into the monosaccharides glucose and galactose is associated with a single nucleotide polymorphism (C/T-13910) 14-kb upstream of the lactase gene (LCT) locus (Enattah et al., 2002).
As fructose is a monosaccharide, there is no enzymatic breakdown needed for its intestinal absorption. The GLUT-5 protein is a specific fructose transporter in the small bowel, which is limited in its transport capacity (Barrett and Gibson, 2012, Jones et al., 2011). Since there is no genetic approach to fructose malabsorption testing, this gastrointestinal condition can only be detected using a functional hydrogen (H2)/methane (CH4) breath test (Gasbarrini et al., 2009). In individuals with fructose malabsorption and lactose malabsorption the non-absorbed carbohydrates reach the large intestine, where colonic bacteria generate degradation products such as short-chain fatty acids, carbon dioxide (CO2), H2, and CH4 (Eisenmann et al., 2008). Furthermore, lactose and fructose molecules are also considered to interact with the tryptophan (TRP) availability by building non-absorbable carbohydrate-TRP complexes in the gastrointestinal tract (Ledochowski et al., 1998a, Ledochowski et al., 1998b; Varea et al., 2005).
TRP is metabolized via the kynurenine (KYN) pathway. The cytokine-induced enzyme indoleamine 2,3-dioxygenase (IDO) converts TRP into KYN, which is metabolized into the neuroprotective kynuric acid (KYNA) and several neurotoxins (Gabbay et al., 2010). The tryptophan break down index (= KYN/TRP) represents the activity of IDO (Myint et al., 2007a, Myint et al., 2007b), which is induced in the blood and in the brain by the increased production of cytokines in individuals with depression (Maes et al., 2011). The tryptophan index (= 100 × TRP/sum of TRP competing amino acids: valine, leucine, isoleucine, tyrosine, phenylalanine) indicates the TRP availability in the brain and the ratio between KYNA and KYN is calculated to assess the neuroprotective ratio (Myint et al., 2012).
A previous study comprising fifty adults reported that fructose malabsorption is associated with lower TRP serum concentrations, which may play an essential role in the development of depressive disorders (Ledochowski et al., 2001). Nevertheless, study designs investigating the serum levels of TRP and TRP metabolites in large cohorts of patients with carbohydrate malabsorption are still lacking.
The aim of the present study was to investigate the association between primary-adult lactose malabsorption, fructose malabsorption, TRP metabolism and the signs of depression in a large cohort of adult patients who were referred to our outpatient clinic for carbohydrate malabsorption testing.
Section snippets
Study design and patients
The data of this prospective study were collected from August 25, 2015 to May 31, 2016. A total of 251 adult patients, who were referred by general practitioners and specialists for primary-adult lactose malabsorption and fructose malabsorption testing to our outpatient clinic, were included. All participants provided their written informed consent. They underwent genotyping for the lactase LCT C/T-13910 polymorphism, 25 g fructose H2/CH4 breath test, and blood sampling after an overnight
Study population characteristics
Of all 251 study participants, 91 (36.25%) were male and 160 (63.75%) were female. The median age was 39 (range: 18–70) years. The baseline characteristics of the metric variables of the study population are shown in Table 1. In total, 155 (61.75%) and 96 (38.25%) out of 251 study participants were found with a BDI II score ≤ 13 and > 13, respectively.
All in all, 44/251 individuals (17.5%) had a positive case history of gastrointestinal disorders (gastritis: 34 [13.5%], reflux esophagitis: 3
Discussion
In the present study, 251 ambulatory adult patients, who were referred by general practitioners and specialists for primary-adult lactose malabsorption and fructose malabsorption testing to our outpatient clinic, were also investigated for TRP metabolism and signs of depression. To the best of our knowledge, this is the largest study cohort addressing the possible associations between carbohydrate malabsorption, TRP metabolism and signs of depression. In comparison, previous published studies
Conflict of interest
The authors declare that there was no conflict of interest regarding the publication of this article.
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