Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with autism spectrum disorders

Lijuan Quan, Jinping Yi, Yue Zhao, Feng Zhang, Xiao Tong Shi, Zhen Feng, Haylie L. Miller

Research output: Contribution to journalArticle

Abstract

Objective: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. Methods: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3–8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. Results: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4–6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0–5.6) μmol/l and 3.0 (2.0–4.4) μmol/l, respectively (P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54; 95% confidence intervals [CI]: 1.32–1.78; P < 0.001) and 27% (1.27 [1.10–1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5–4.9] μmol/l vs. 4.5(3.7–6.0) μmol/l; P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28–2.01], P < 0.001) and 31% (1.31 [1.08–1.49], P < 0.001), respectively. Conclusions: Elevated plasma levels of TMAO were associated with ASD and symptom severity.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalNeuroToxicology
Volume76
DOIs
StatePublished - Jan 2020

Fingerprint

Metabolites
Phosphatidylcholines
Plasmas
Odds Ratio
trimethyloxamine
Gastrointestinal Microbiome
Autism Spectrum Disorder
Confidence Intervals
High performance liquid chromatography
Regression analysis
Mass spectrometry
Logistics
Autistic Disorder
Tandem Mass Spectrometry
Association reactions
Logistic Models
High Pressure Liquid Chromatography
Regression Analysis
Chemical analysis

Keywords

  • Autism spectrum disorder
  • Chinese
  • Gut microbiota
  • Trimethylamine N-oxide

Cite this

Quan, Lijuan ; Yi, Jinping ; Zhao, Yue ; Zhang, Feng ; Shi, Xiao Tong ; Feng, Zhen ; Miller, Haylie L. / Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with autism spectrum disorders. In: NeuroToxicology. 2020 ; Vol. 76. pp. 93-98.
@article{98a35633169249cdb2b952b3c5b49a12,
title = "Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with autism spectrum disorders",
abstract = "Objective: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. Methods: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3–8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. Results: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4–6 years) and 129 (78.7{\%}) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0–5.6) μmol/l and 3.0 (2.0–4.4) μmol/l, respectively (P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54{\%} (with the odds ratios [OR] of 1.54; 95{\%} confidence intervals [CI]: 1.32–1.78; P < 0.001) and 27{\%} (1.27 [1.10–1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2{\%}). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8{\%}) whose symptoms were classified as severe (CARS > 36) (3.5[2.5–4.9] μmol/l vs. 4.5(3.7–6.0) μmol/l; P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61{\%} (with the OR of 1.61 [95{\%} CI 1.28–2.01], P < 0.001) and 31{\%} (1.31 [1.08–1.49], P < 0.001), respectively. Conclusions: Elevated plasma levels of TMAO were associated with ASD and symptom severity.",
keywords = "Autism spectrum disorder, Chinese, Gut microbiota, Trimethylamine N-oxide",
author = "Lijuan Quan and Jinping Yi and Yue Zhao and Feng Zhang and Shi, {Xiao Tong} and Zhen Feng and Miller, {Haylie L.}",
year = "2020",
month = "1",
doi = "10.1016/j.neuro.2019.10.012",
language = "English",
volume = "76",
pages = "93--98",
journal = "NeuroToxicology",
issn = "0161-813X",
publisher = "Elsevier",

}

Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with autism spectrum disorders. / Quan, Lijuan; Yi, Jinping; Zhao, Yue; Zhang, Feng; Shi, Xiao Tong; Feng, Zhen; Miller, Haylie L.

In: NeuroToxicology, Vol. 76, 01.2020, p. 93-98.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plasma trimethylamine N-oxide, a gut microbe–generated phosphatidylcholine metabolite, is associated with autism spectrum disorders

AU - Quan, Lijuan

AU - Yi, Jinping

AU - Zhao, Yue

AU - Zhang, Feng

AU - Shi, Xiao Tong

AU - Feng, Zhen

AU - Miller, Haylie L.

PY - 2020/1

Y1 - 2020/1

N2 - Objective: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. Methods: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3–8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. Results: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4–6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0–5.6) μmol/l and 3.0 (2.0–4.4) μmol/l, respectively (P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54; 95% confidence intervals [CI]: 1.32–1.78; P < 0.001) and 27% (1.27 [1.10–1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5–4.9] μmol/l vs. 4.5(3.7–6.0) μmol/l; P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28–2.01], P < 0.001) and 31% (1.31 [1.08–1.49], P < 0.001), respectively. Conclusions: Elevated plasma levels of TMAO were associated with ASD and symptom severity.

AB - Objective: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. Methods: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3–8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. Results: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4–6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0–5.6) μmol/l and 3.0 (2.0–4.4) μmol/l, respectively (P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54; 95% confidence intervals [CI]: 1.32–1.78; P < 0.001) and 27% (1.27 [1.10–1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5–4.9] μmol/l vs. 4.5(3.7–6.0) μmol/l; P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28–2.01], P < 0.001) and 31% (1.31 [1.08–1.49], P < 0.001), respectively. Conclusions: Elevated plasma levels of TMAO were associated with ASD and symptom severity.

KW - Autism spectrum disorder

KW - Chinese

KW - Gut microbiota

KW - Trimethylamine N-oxide

UR - http://www.scopus.com/inward/record.url?scp=85074600054&partnerID=8YFLogxK

U2 - 10.1016/j.neuro.2019.10.012

DO - 10.1016/j.neuro.2019.10.012

M3 - Article

C2 - 31704102

AN - SCOPUS:85074600054

VL - 76

SP - 93

EP - 98

JO - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

ER -