Longitudinal relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals

Abstract

Amino acid metabolites in biofluids are associated with high body mass index (BMI) and cardiometabolic abnormalities. However, prospective investigations regarding these associations are few, particularly among young individuals. Moreover, little is presently known about the impact of long-term high BMI. Using data from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study (111 males and 107 females), we prospectively investigated relations between repeatedly measured urinary levels of 33 metabolites and (1) previously identified long-term BMI trajectory groups from childhood into late adolescence and (2) cardiometabolic risk markers in late adolescence-young adulthood, in sex-specific linear mixed regression models. Males with long-term overweight had lower indole-3-acetic acid when compared to others. Further, methionine, isoleucine, tryptophan, xanthurenic acid, and indole-3-carboxaldehyde were negatively associated with C-reactive protein (CRP), but 5-hydroxyindole-3-acetic acid was positively associated with CRP. No associations were observed in females. Long-term overweight from childhood into late adolescence is associated with decreased urinary levels of gut bacteria-derived indole-3-acetic acid, and several urinary amino acids, including gut bacteria-derived indole-3-carboxaldehyde are associated with elevated CRP later on in life. taken together, our data suggest that indole metabolites, and their gut bacteria producers play potentially important roles in overweight-related inflammation. High body mass index (BMI) during childhood and adolescence is still a major public health concern 1,2. The condition contributes to the development of cardiometabolic abnormalities such as inflammation over the life course 3. Dysregulated metabolism is one of the biological mechanisms through which high BMI contributes to the development of these cardiometabolic abnormalities 4,5. Scientific efforts have focused on carbohydrate and lipid metabolic perturbations as one of these mechanisms, interest in the impact of unfavorable alterations in protein/amino acid metabolism is now emerging 6,7. Therefore, it would be necessary to explore the link of high BMI, amino acid metabolites, and cardiometabolic abnormalities.

Associations of BMI and Body Fat with Urine Metabolome in Adolescents Are Sex-Specific: A Cross-Sectional Study

“…In general, our results reinforced the idea of sexual dimorphism in metabolism. The stronger association in males is consistent with previous studies in mice [ 3 ], adults [ 4 , 5 ], and adolescents [ 6 ], as well as our own recent findings within this study population [ 7 ]. One potential explanation is that sex hormones might modify the relationship between body composition and the urine metabolome.…”

“…Being overweight is known to be related to metabolic changes—for example, through body fat functioning as an endocrine organ, producing adipokines like leptin or visfatin [ 6 , 7 ]. Additionally, past studies have shown that overweightness is likely to be a causal influence on the metabolome phenotype [ 8 ].…”

“…Additionally, past studies have shown that overweightness is likely to be a causal influence on the metabolome phenotype [ 8 ]. A recent review [ 7 ] that summarizes the current knowledge of the metabolomic signature of adult obesity concluded that many metabolite groups are altered, including sexual steroids, amino acids, and acylcarnitines, among others. Interestingly, only a few epidemiological studies have explored the relationship between body composition and the metabolome in adolescents [ 9 , 10 ].…”

An Investigation into the Temporal Reproducibility of Tryptophan Metabolite Networks Among Healthy Adolescents

“…For this present study, we considered a subset of participants from which the concentration levels of a set of metabolites were repeatedly profiled by a targeted metabolomic approach in 24-hours urine samples. 8 These metabolites included tryptophan and 18 of its metabolites. We considered 132 individuals from whom these metabolites were profiled at 2-time points, ages 17 and 18 years.…”

“…1 In the last years, tryptophan and its bioactive metabolites have attracted growing attention due to their association with health conditions such as systemic inflammation, cardiometabolic diseases, and neurodegenerative disorders. [1][2][3][4][5][6][7][8] These metabolites arise from the 3 major host and microbial metabolic pathways of tryptophan catabolism: the oxidative or kynurenine pathway, the hydroxylation or serotonin pathway, and the microbialderived indole pathway. 6,[9][10][11] There is cross-talk 12,13 and a balanced interplay 14 among these aforementioned pathways.…”