Identification of enterotype for patients with Alzheimer’s disease

Abstract Background Alzheimer’s disease (AD) is a progressive and chronic neurodegenerative disorder of the central nervous system, characterized by behavioral and dysexecutive deficits. Its pathogenesis is closely associated with the intestinal flora. This study aimed to explore the enterotypes in...

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Main Authors: Guang-sheng Liu, Yang Song, Jin-sheng Yan, Yi-jie Chai, Yun-fei Zhao, Huan Ma
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Translational Medicine
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Online Access:https://doi.org/10.1186/s12967-025-06343-3
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author Guang-sheng Liu
Yang Song
Jin-sheng Yan
Yi-jie Chai
Yun-fei Zhao
Huan Ma
author_facet Guang-sheng Liu
Yang Song
Jin-sheng Yan
Yi-jie Chai
Yun-fei Zhao
Huan Ma
author_sort Guang-sheng Liu
collection DOAJ
description Abstract Background Alzheimer’s disease (AD) is a progressive and chronic neurodegenerative disorder of the central nervous system, characterized by behavioral and dysexecutive deficits. Its pathogenesis is closely associated with the intestinal flora. This study aimed to explore the enterotypes in AD by identifying key bacteria through machine learning and species co-occurrence network analysis. Methods The collection of fecal samples from AD patients was followed by 16 S rRNA analysis using QIIME2. Enterotype clustering was conducted at the genus level, and deep neural network (DNN) classification models were developed for AD and healthy controls within each enterotype. Results Analysis of three 16 S rRNA gut microbiome datasets identified three distinct enterotypes: Escherichia_Shigella (ET-E), Faecalibacterium (ET-F), and Bacteroides (ET-B). The ET-E is mainly characterized by the absence of Akkermansia in AD group. The Akkermansia was significantly positively correlated with Eubacterium_coprostanoligenes_group and negatively correlated with biosynthesis and amino acid metabolism. The ET-F highly expressed Agathobacter, un_f__Lachnospiraceae, Lachnoclostridium, and low expressed Dorea in AD group. Among them, Agathobacter was significantly positively correlated with un_f__Lachnospiraceae, and un_f__Lachnospiraceae was significantly positively correlated with Lachnoclostridium. The Dorea was significantly negatively correlated with Lachnoclostridium. The AD from ET-B group had high expression of two beneficial bacteria, Butyricicoccus and Parabacteroides. The findings suggest that the ET-E enterotype may predispose individuals to AD, with Akkermansia identified as a potential risk factor. Conversely, the ET-B enterotype appears to be associated with milder symptoms, with Butyricicoccus and Parabacteroides potentially serving as protective factors. Therefore, a comprehensive understanding of the species characteristics and interactions within different enterotypes is essential for modulating the gut-brain axis and mitigating AD symptoms.
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spelling doaj-art-c80a33cdec414876a697af20521235972025-08-20T02:56:09ZengBMCJournal of Translational Medicine1479-58762025-03-0123111210.1186/s12967-025-06343-3Identification of enterotype for patients with Alzheimer’s diseaseGuang-sheng Liu0Yang Song1Jin-sheng Yan2Yi-jie Chai3Yun-fei Zhao4Huan Ma5Department of Neurosurgery, The Second Hospital of Shanxi Medical UniversityDepartment of Neurosurgery, Linfen People’s HospitalDepartment of Neurosurgery, The Second Hospital of Shanxi Medical UniversityThe Second Clinical School of Medicine, Shanxi Medical UniversityDepartment of Neurology, The Second Hospital of Shanxi Medical UniversityDepartment of Anesthesiology, The Second Hospital of Shanxi Medical UniversityAbstract Background Alzheimer’s disease (AD) is a progressive and chronic neurodegenerative disorder of the central nervous system, characterized by behavioral and dysexecutive deficits. Its pathogenesis is closely associated with the intestinal flora. This study aimed to explore the enterotypes in AD by identifying key bacteria through machine learning and species co-occurrence network analysis. Methods The collection of fecal samples from AD patients was followed by 16 S rRNA analysis using QIIME2. Enterotype clustering was conducted at the genus level, and deep neural network (DNN) classification models were developed for AD and healthy controls within each enterotype. Results Analysis of three 16 S rRNA gut microbiome datasets identified three distinct enterotypes: Escherichia_Shigella (ET-E), Faecalibacterium (ET-F), and Bacteroides (ET-B). The ET-E is mainly characterized by the absence of Akkermansia in AD group. The Akkermansia was significantly positively correlated with Eubacterium_coprostanoligenes_group and negatively correlated with biosynthesis and amino acid metabolism. The ET-F highly expressed Agathobacter, un_f__Lachnospiraceae, Lachnoclostridium, and low expressed Dorea in AD group. Among them, Agathobacter was significantly positively correlated with un_f__Lachnospiraceae, and un_f__Lachnospiraceae was significantly positively correlated with Lachnoclostridium. The Dorea was significantly negatively correlated with Lachnoclostridium. The AD from ET-B group had high expression of two beneficial bacteria, Butyricicoccus and Parabacteroides. The findings suggest that the ET-E enterotype may predispose individuals to AD, with Akkermansia identified as a potential risk factor. Conversely, the ET-B enterotype appears to be associated with milder symptoms, with Butyricicoccus and Parabacteroides potentially serving as protective factors. Therefore, a comprehensive understanding of the species characteristics and interactions within different enterotypes is essential for modulating the gut-brain axis and mitigating AD symptoms.https://doi.org/10.1186/s12967-025-06343-3Alzheimer’s diseaseEnterotypesGut microbiomeAkkermansiaButyricicoccusParabacteroides
spellingShingle Guang-sheng Liu
Yang Song
Jin-sheng Yan
Yi-jie Chai
Yun-fei Zhao
Huan Ma
Identification of enterotype for patients with Alzheimer’s disease
Journal of Translational Medicine
Alzheimer’s disease
Enterotypes
Gut microbiome
Akkermansia
Butyricicoccus
Parabacteroides
title Identification of enterotype for patients with Alzheimer’s disease
title_full Identification of enterotype for patients with Alzheimer’s disease
title_fullStr Identification of enterotype for patients with Alzheimer’s disease
title_full_unstemmed Identification of enterotype for patients with Alzheimer’s disease
title_short Identification of enterotype for patients with Alzheimer’s disease
title_sort identification of enterotype for patients with alzheimer s disease
topic Alzheimer’s disease
Enterotypes
Gut microbiome
Akkermansia
Butyricicoccus
Parabacteroides
url https://doi.org/10.1186/s12967-025-06343-3
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AT yijiechai identificationofenterotypeforpatientswithalzheimersdisease
AT yunfeizhao identificationofenterotypeforpatientswithalzheimersdisease
AT huanma identificationofenterotypeforpatientswithalzheimersdisease