Altered gut microbial metabolites in amnestic mild cognitive impairment and alzheimer’s disease: Signals in host–microbe interplay

Li Wu, Yuqiu Han, Zhipeng Zheng, Guoping Peng, Ping Liu, Siqing Yue, Shuai Zhu, Jun Chen, Hanying Lv, Lifang Shao, Yan Sheng, Yulan Wang, Liang Li, Lanjuan Li, Baohong Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

143 Citations (Scopus)

Abstract

Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.

Original languageEnglish
Article number228
Pages (from-to)1-15
Number of pages15
JournalNutrients
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

ASJC Scopus Subject Areas

  • Food Science
  • Nutrition and Dietetics

Keywords

  • Alzheimer’s disease
  • Fecal metabolomics
  • Intestinal microbiota
  • Short-chain fatty acids
  • Tryptophan

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