Dataset Information

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer's Disease.

ABSTRACT: Gut bacterial dysbiosis plays a vital role in the development of Alzheimer's disease (AD). However, our understanding of alterations to the gut fungal microbiota and their correlations with host immunity in AD is still limited. Samples were obtained from 88 Chinese patients with AD, and 65 age- and gender-matched, cognitively normal controls. Using these samples, we investigated the fungal microbiota targeting internal transcribed spacer 2 (ITS2) rRNA genes using MiSeq sequencing, and analyzed their associations with the host immune response. Our data demonstrated unaltered fungal diversity but altered taxonomic composition of the fecal fungal microbiota in the AD patients. The analysis of the fungal microbiota was performed using 6,585,557 high-quality reads (2,932,482 reads from the controls and 3,653,075 from the AD patients), with an average of 43,042 reads per sample. We found that several key differential fungi such as Candida tropicalis and Schizophyllum commune were enriched in the AD patients, while Rhodotorula mucilaginosa decreased significantly. Interestingly, C. tropicalis and S. commune were positively correlated with IP-10 and TNF-? levels. In contrast, C. tropicalis was negatively correlated with IL-8 and IFN-? levels, and R. mucilaginosa was negatively correlated with TNF-? level. PiCRUSt analysis revealed that lipoic acid metabolism, starch and sucrose metabolism were significantly decreased in the AD fungal microbiota. This study is the first to demonstrate fecal fungal dysbiosis in stable AD patients at a deeper level, and to identify the key differential fungi involved in regulating host systemic immunity. The analysis of the fungal microbiota in AD performed here may provide novel insights into the etiopathogenesis of AD and pave the way for improved diagnosis and treatment of AD.

SUBMITTER: Ling Z

PROVIDER: S-EPMC7876328 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer's Disease.

Ling Zongxin Z Zhu Manlian M Liu Xia X Shao Li L Cheng Yiwen Y Yan Xiumei X Jiang Ruilai R Wu Shaochang S

Frontiers in cell and developmental biology 20210128

Gut bacterial dysbiosis plays a vital role in the development of Alzheimer's disease (AD). However, our understanding of alterations to the gut fungal microbiota and their correlations with host immunity in AD is still limited. Samples were obtained from 88 Chinese patients with AD, and 65 age- and gender-matched, cognitively normal controls. Using these samples, we investigated the fungal microbiota targeting internal transcribed spacer 2 (ITS2) rRNA genes using MiSeq sequencing, and analyzed t ...[more]

PMID: 33585471

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Project description:Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut-brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium, increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.

Project description:Schizophrenia (SZ) is a severe neuropsychiatric disorder with largely unknown etiology and pathogenesis. Mounting preclinical and clinical evidence suggests that the gut microbiome is a vital player in SZ. However, the gut microbiota characteristics and its host response in elderly SZ patients are still not well understood. A total of 161 samples was collected, including 90 samples from elderly SZ patients and 71 samples from healthy controls. We explored the gut microbiota profiles targeting the V3-V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with host immune response. Our data found that bacterial β-diversity analyses could divide the SZ patients and healthy controls into two different clusters. The Linear discriminant analysis Effect Size (LEfSe) identified the compositional changes in SZ-associated bacteria, including Faecalibacterium, Roseburia, Actinomyces, Butyricicoccus, Prevotella and so on. In addition, the levels of pro-inflammatory cytokines such as IL-1β were greatly increased in SZ patients while the levels of anti-inflammatory cytokines such as IFN-γ were markedly decreased. Correlation analysis suggested that these bacteria contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the SZ patients from healthy controls. Moreover, several predicted functional modules, including increased lipopolysaccharide biosynthesis, folate biosynthesis, lipoic acid metabolism, and decreased bile acid biosynthesis, fatty acid biosynthesis in SZ-associated microbiota, could be utilized by the bacteria to produce immunomodulatory metabolites. This study, for the first time, demonstrated the structural and functional dysbiosis of the fecal microbiota in Chinese elderly SZ patients, suggesting the potential for using gut key functional bacteria for the early, non-invasive diagnosis of SZ, personalized treatment, and the development of tailor-made probiotics designed for Chinese elderly SZ patients.

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Dataset Information

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer's Disease.

Publications

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer's Disease.

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