Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder

Zhu, Jiang; Hua, Xueying; Yang, Ting; Guo, Min; Qiu, Li Xin; Xiao, Lü; Li, Ling; Chen, Jie; Li, Tingyu

doi:10.1007/s10803-021-05066-w

Cited by 25 publications

(21 citation statements)

References 56 publications

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“…Angelis et al reported elevated levels of tryptophan and 3‐methylindole in the feces of children with ASD (De Angelis et al, 2013). Besides, 8‐hydroxy‐2′‐deoxyguanosine, which is a sensitive marker of oxidative DNA damage, was found to be significantly increased in children with ASD (Zhu et al, 2021). Overall, the suggested metabolic impairment may contribute to the risk of ASD.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we found that amino acid metabolism and cofactors and vitamin metabolism were enriched in the ASD group. Abnormal amino acid and vitamin metabolism pathways have been reported in multiple studies (Muller et al, 2016;Zhu et al, 2021). Angelis et al reported elevated levels of tryptophan and 3-methylindole in the feces of children with ASD (De Angelis et al, 2013).…”

Section: Disturbed Pathways Between Children With Asd and Healthy Con...mentioning

confidence: 99%

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Alteration of the fecal microbiota in Chinese children with autism spectrum disorder

Xie

et al. 2022

Autism Research

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Autism spectrum disorder (ASD) is associated with altered gut microbiota. However, there has been little consensus on the altered bacterial species and studies have had small sample sizes. We aimed to identify the taxonomic composition and evaluate the changes in the fecal microbiota in Chinese children with ASD by using a relatively large sample size. We conducted a case–control study of 101 children with ASD and 103 healthy controls in China. Demographic information and fecal samples were collected, and the V3‐V4 hypervariable regions of the bacterial 16S ribosomal RNA (rRNA) gene were sequenced. The alpha and beta diversities between the two groups were significantly different. After correcting for multiple comparisons, at the phylum level the relative abundances of Actinobacteria and Proteobacteria in the case group were significantly higher than those in the control group. The relative abundance of the Escherichia‐Shigella genus in the case group was significantly higher than that of the control group, and the relative abundance of Blautia and unclassified_f__Lachnospiraceae in the control group were higher than that of the case group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that children with ASD may have disturbed functional pathways, such as amino acid metabolism, cofactor and vitamin metabolism, and the AMP‐activated protein kinase signaling pathway. This study revealed the characteristics of the intestinal flora of Chinese children with ASD and provided further evidence of gut microbial dysbiosis in ASD. Lay Summary This study characterized the gut microbiota composition of 101 children with ASD and 103 healthy controls in China. The altered gut microbiota may contribute significantly to the risk of ASD, including significant increases in the relative abundances of Actinobacteria, Proteobacteria and Escherichia‐Shigella and significant decrease of Blautia and unclassified_f__Lachnospiraceae. This study provided further evidence of gut microbial dysbiosis in ASD.

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Section: Discussionmentioning

confidence: 99%

Section: Disturbed Pathways Between Children With Asd and Healthy Con...mentioning

confidence: 99%

Alteration of the fecal microbiota in Chinese children with autism spectrum disorder

Xie

et al. 2022

Autism Research

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“…We compared the age- and sex-matched differential ranking analysis to the standard group-averaged differential ranking analysis across eight out of the ten 16S studies [47, 48, 49, 21, 50, 51, 52, 53]. Age- and sex-matched differential analysis outperformed standard group averaging with respect to R 2 , and its overall performance strictly improved as more studies were added (Figure S1).…”

Section: Resultsmentioning

confidence: 99%

“…Several dozen autism gut metagenomics studies have revealed many, albeit inconsistent, variations in microbial diversity in individuals with ASD compared with neurotypical individuals [18, 19, 17]. Similarly, metagenome-based functional reconstructions and metabolic analyses have also shown strong, albeit inconclusive differences between ASD and neurotypical individuals [20, 21, 22]. Comparative analyses at other omic levels have further shown little agreement across studies [23] raising the question of whether the results obtained so far reflect intrinsic biological differences among cohorts, insufficient statistical power, or experimental biases that preclude meaningful comparisons [24].…”

Section: Introductionmentioning

confidence: 99%

Multi-omic analysis along the gut-brain axis points to a functional architecture of autism

Morton

Jin

Mills³

et al. 2022

Preprint

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Autism is a highly heritable neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in autism, with dozens of cross-sectional microbiome and other omic studies revealing autism-specific profiles along the GBA albeit with little agreement in composition or magnitude. To explore the functional architecture of autism, we developed an age and sex-matched Bayesian differential ranking algorithm that identified autism-specific profiles across 10 cross-sectional microbiome datasets and 15 other omic datasets, including dietary patterns, metabolomics, cytokine profiles, and human brain expression profiles. The analysis uncovered a highly significant, functional architecture along the GBA that encapsulated the overall heterogeneity of autism phenotypes. This architecture was determined by autism-specific amino acid, carbohydrate and lipid metabolism profiles predominantly encoded by microbial species in the genera Prevotella, Enterococcus, Bifidobacterium, and Desulfovibrio, and was mirrored in brain-associated gene expression profiles and restrictive dietary patterns in individuals with autism. Pro-inflammatory cytokine profiling and virome association analysis further supported the existence of an autism-specific architecture associated with particular microbial genera. Re-analysis of a longitudinal intervention study in autism recapitulated the cross-sectional profiles, and showed a strong association between temporal changes in microbiome composition and autism symptoms. Further elucidation of the functional architecture of autism, including of the role the microbiome plays in it, will require deep, multi-omic longitudinal intervention studies on well-defined stratified cohorts to support causal and mechanistic inference.

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“…Vitamin B6 is a cofactor of KYNU and KAT. In the KP process, except for 3-HK, all metabolites depend on vitamin B6 to produce, including 5-HT and melatonin (57)(58)(59). Vitamin B3 deficiency can lead to mental disorders, and this effect is mostly related to TRP metabolism.…”

Section: Vitaminsmentioning

confidence: 99%

Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders

Long

et al. 2022

Front. Immunol.

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Neurological and psychiatric disorders are a category of chronic diseases that are widespread and pose serious mental and physical health problems for patients. The substrates, products, and enzymes of Tryptophan metabolism all contribute to the development of neurological and psychiatric disorders. This paper deals with three metabolic pathways of tryptophan that produce a series of metabolites called tryptophan Catabolics (TRYCATs). These metabolites are involved in pathological processes such as excitotoxicity, neuroinflammation, oxidative stress, and mitochondrial damage and are closely associated with neurological and psychiatric disorders such as Alzheimer’s disease and depression. Here, we review the elements that affect how tryptophan metabolism is regulated, including inflammation and stress, exercise, vitamins, minerals, diet and gut microbes, glucocorticoids, and aging, as well as the downstream regulatory effects of tryptophan metabolism, including the regulation of glutamate (Glu), immunity, G-protein coupled receptor 35 (Gpr35), nicotinic acetylcholine receptor (nAChR), aryl hydrocarbon receptor (AhR), and dopamine (DA). In order to advance the general understanding of tryptophan metabolism in neurological and psychiatric disorders, this paper also summarizes the current situation and effective drugs of tryptophan metabolism in the treatment of neurological and psychiatric disorders and considers its future research prospects.

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Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder

Cited by 25 publications

References 56 publications

Alteration of the fecal microbiota in Chinese children with autism spectrum disorder

Alteration of the fecal microbiota in Chinese children with autism spectrum disorder

Multi-omic analysis along the gut-brain axis points to a functional architecture of autism

Tryptophan metabolism: Mechanism-oriented therapy for neurological and psychiatric disorders

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