Analysis of the relationship between the gut microbiome and dementia: a cross-sectional study conducted in Japan

Naoki Saji, Shumpei Niida, Kenta Murotani, Takayoshi Hisada, Tsuyoshi Tsuduki, Taiki Sugimoto, Ai Kimura, Kenji Toba, Takashi Sakurai, Naoki Saji, Shumpei Niida, Kenta Murotani, Takayoshi Hisada, Tsuyoshi Tsuduki, Taiki Sugimoto, Ai Kimura, Kenji Toba, Takashi Sakurai

Abstract

Dysregulation of the gut microbiome is associated with several life-threatening conditions and thus might represent a useful target for the prevention of dementia. However, the relationship between the gut microbial population and dementia has not yet been fully clarified. We recruited outpatients visiting our memory clinic to participate in this study. Information on patient demographics, risk factors, and activities of daily living was collected, and cognitive function was assessed using neuropsychological tests and brain magnetic resonance imaging scans. Faecal samples were obtained, and the gut microbiome was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, one of the most well-established and reliable 16S ribosomal RNA-based methods for classifying gut microbiota. Patients were divided into two groups, demented and non-demented. Multivariable logistic regression models were used to identify the variables independently associated with dementia. The T-RFLP analysis revealed differences in the composition of the gut microbiome: the number of Bacteroides (enterotype I) was lower and the number of 'other' bacteria (enterotype III) was higher in demented than non-demented patients. Multivariable analyses showed that the populations of enterotype I and enterotype III bacteria were strongly associated with dementia, independent of the traditional dementia biomarkers. Further studies of the metabolites of gut microbes are needed to determine the mechanism underlying this association.

Conflict of interest statement

Dr. Saji has received grants from the NARO Bio-oriented Technology Research Advancement Institution project (Advanced integration research for agriculture and interdisciplinary fields), the BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program, and grants from the Toyoaki Scholarship Foundation. Dr. Saji, Dr. Niida and Dr. Sakurai have received research grants from the Research Funding of Longevity Sciences from the National Center for Geriatrics and Gerontology. Dr. Saji, Dr. Niida, Dr. Toba and Dr. Sakurai have received research funds for Comprehensive Research on Aging and Health from the Japan Agency for Medical Research and Development (AMED). Dr. Tsuduki has received grants from the NARO Bio-oriented Technology Research Advancement Institution project (Advanced Integration Research for Agriculture and Interdisciplinary Fields).

Figures

Figure 1
Figure 1
Dendrogram of the gut microbiome. A comparison of the gut microbiome between demented and non-demented patients demonstrates two major clusters of microbial taxa.
Figure 2
Figure 2
(A) Distribution of the gut microbiota. (B) Frequency of each enterotype in the dementia and non-dementia groups. Enterotype I (Bacteroides >30%) was enriched in the non-dementia group.
Figure 3
Figure 3
Comparison of the gut microbiota between the dementia and non-dementia groups. The percentages of each taxon of gut microbe was compared. The percentage of Bacteroides was significantly lower in the dementia than the non-dementia group.

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