Tryptophan status in autism spectrum disorder and the influence of supplementation on its level

Kałużna–Czaplińska, Joanna; Jóźwik-Pruska, Jagoda; Chirumbolo, Salvatore; Bjørklund, Geir

doi:10.1007/s11011-017-0045-x

Cited by 50 publications

(48 citation statements)

References 56 publications

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“…It is worth noting that ketogenic amino acid metabolism (lysine degradation and tryptophan metabolism) was reduced in ASD children compared to in the controls. Tryptophan is an essential amino acid, which can be metabolized into the neurotransmitter serotonin [Kaluzna-Czaplinska, Jozwik-Pruska, Chirumbolo, & Bjorklund, 2017]. Decreased tryptophan metabolism had been observed in ASD patients cells, which may alter brain development, neuroimmune activity and mitochondrial function [Boccuto et al, 2013].…”

Section: Discussionmentioning

confidence: 99%

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

et al. 2020

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Alterations in the gut microbiota may influence gastrointestinal (GI) dysbiosis frequently reported in individuals with autism spectrum disorder (ASD). In this study, we sequenced the bacterial 16S rRNA gene to evaluate changes in fecal microbiota between 48 children with ASD and 48 healthy children in China. At the phylum level, the number of Firmicutes, Proteobacteria, and Verrucomicrobia decreased in children with ASD, while the Bacteroidetes/Firmicutes was significantly higher in autistic children due to enrichment of Bacteroidetes. At the genus level, the amount of Bacteroides, Prevotella, Lachnospiracea_incertae_sedis, and Megamonas increased, while Clostridium XlVa, Eisenbergiella, Clostridium IV, Flavonifractor, Escherichia/Shigella, Haemophilus, Akkermansia, and Dialister decreased in children with ASD relative to the controls. Significant increase was observed in the number of species synthesizing branched‐chain amino acids (BCAAs), like Bacteroides vulgatus and Prevotella copri, while the numbers of Bacteroides fragilis and Akkermansia muciniphila decreased in children with ASD compared to the controls. Most importantly, the highest levels of pathogenic bacteria were different for each child with ASD in this cohort. We found that only one functional module, cellular antigens, was enriched in children with ASD, and other pathways like lysine degradation and tryptophan metabolism were significantly decreased in children with ASD. These findings provide further evidence of altered gut microbiota in Chinese ASD children and may contribute to the treatment of patients with ASD. Lay Summary This study characterized the gut bacteria composition of 48 children with ASD and 48 neurotypical children in China. The metabolic disruptions caused by altered gut microbiota may contribute significantly to the neurological pathophysiology of ASD, including significant increases in the number of species synthesizing BCAAs, and decreases in the number of probiotic species. These findings suggest that a gut microbiome‐associated therapeutic intervention may provide a novel strategy for treating GI symptoms frequently seen in individuals with ASD. Autism Res 2020, 13: 1614–1625. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

et al. 2020

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“…To help clarify the potential relationship between tryptophan impairment and the severity of autistic symptoms, Kałużna-Czaplińska et al 78 examined the retention status of supplemented tryptophan and the correlation between the supplementation of the diet with B vitamins and magnesium and the level of the excreted (excess) tryptophan in patients with autism spectrum disorder. Statistical correlations were observed between tryptophan levels and the severity of symptoms in different groups of patients.…”

Section: Possible Roles Of Tryptophan In the Diagnosis And Mitigationmentioning

confidence: 99%

Analysis, Nutrition, and Health Benefits of Tryptophan

Friedman

2018

Int J�Tryptophan�Res

188

132

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Tryptophan is an essential plant-derived amino acid that is needed for the in vivo biosynthesis of proteins. After consumption, it is metabolically transformed to bioactive metabolites, including serotonin, melatonin, kynurenine, and the vitamin niacin (nicotinamide). This brief integrated overview surveys and interprets our current knowledge of the reported multiple analytical methods for free and protein-bound tryptophan in pure proteins, protein-containing foods, and in human fluids and tissues, the nutritional significance of l-tryptophan and its isomer d-tryptophan in fortified infant foods and corn tortillas as well the possible function of tryptophan in the diagnosis and mitigation of multiple human diseases. Analytical methods include the use of acid ninhydrin, near-infrared reflectance spectroscopy, colorimetry, basic hydrolysis; acid hydrolysis of S-pyridylethylated proteins, and high-performance liquid and gas chromatography-mass spectrometry. Also covered are the nutritional values of tryptophan-fortified infant formulas and corn-based tortillas, safety of tryptophan for human consumption and the analysis of maize (corn), rice, and soybean plants that have been successfully genetically engineered to produce increasing tryptophan. Dietary tryptophan and its metabolites seem to have the potential to contribute to the therapy of autism, cardiovascular disease, cognitive function, chronic kidney disease, depression, inflammatory bowel disease, multiple sclerosis, sleep, social function, and microbial infections. Tryptophan can also facilitate the diagnosis of certain conditions such as human cataracts, colon neoplasms, renal cell carcinoma, and the prognosis of diabetic nephropathy. The described findings are not only of fundamental scientific interest but also have practical implications for agriculture, food processing, food safety, nutrition, and animal and human health. The collated information and suggested research need will hopefully facilitate and guide further studies needed to optimize the use of free and protein-bound tryptophan and metabolites to help improve animal and human nutrition and health.

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“…Tryptophan can cross the blood-brain-barrier (BBB) and takes part in the synthesis of serotonin in the central nervous system (CNS). There is evidence that individuals with ASD have low tryptophan concentrations peripherally ( Kałużna-Czaplińska et al, 2017 ). Serotonin itself cannot cross the BBB, even though more than 90 percent is located in enterochromaffin (EC) cells of the gastrointestinal tract ( Gershon and Tack, 2007 ).…”

Section: Main Articlementioning

confidence: 99%

“…Changes in the composition of the microbiome, called “ microbial dysbiosis ,” have been reported in ASD ( Van Sadelhoff et al, 2019 ). We assume that this alteration of composition is linked to an individually reduced availability of tryptophan in general, resulting in low tryptophan levels in ASD ( Kałużna-Czaplińska et al, 2017 ). The reduced availability of tryptophan increases the activation of the sympathetic nervous system by SCFAs, consistent with our assumption of increased ANS and HPA activity.…”

Section: Main Articlementioning

confidence: 99%

The Generalized Adaptation Account of Autism

2020

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The heterogeneous phenomenology of autism together with diverse patterns of comorbidities led in the past to formulation of manifold theories and hypotheses on different explanatory levels. We scrutinize most recent findings from genetics, neurobiology and physiology and derive testable hypotheses about possible physiological links between domains. With focus on altered sensory perception and neuronal processing in ASD, we assume two intertwined regulatory feedback circuits under the umbrella of genetics and environmental factors. Both regulatory circuits are highly variable between individuals in line with the heterogeneous spectrum of ASD. The circuits set off from altered pathways and connectivity in ASD, fueling HPA-axis activity and distress. In the first circuit altered tryptophan metabolism leads to higher neurotoxic substances and reinforces the excitation:inhibition imbalance in the brain. The second circuit focuses on the impact and interaction with the environment and its rhythms in ASD. With lower melatonin levels, as the pacemaker molecule of the circadian system, we assume misalignment to outer and inner states corroborated from the known comorbidities in ASD. Alterations of the microbiome composition in ASD are supposed to act as a regulatory linking factor for both circuits. Overall, we assume that altered internal balance on cellular and neurophysiological levels is one of the main reasons leading to a lower ability in ASD to adapt to the environment and own internal changing states, leading to the conceptualization of autism as a condition of generalized imbalance in adaptation. This comprehensive framework opens up new perspectives on possible intervention and prevention strategies.

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Tryptophan status in autism spectrum disorder and the influence of supplementation on its level

Cited by 50 publications

References 56 publications

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder

Analysis, Nutrition, and Health Benefits of Tryptophan

The Generalized Adaptation Account of Autism

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