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. 2020 May 18;10(1):8088.
doi: 10.1038/s41598-020-65196-6.

Relationship between dementia and gut microbiome-associated metabolites: a cross-sectional study in Japan

Naoki Saji  1 , Kenta Murotani  2 , Takayoshi Hisada  3 , Tadao Kunihiro  3 , Tsuyoshi Tsuduki  4 , Taiki Sugimoto  5 , Ai Kimura  5 , Shumpei Niida  6 , Kenji Toba  5 , Takashi Sakurai  5   7
Affiliations

Relationship between dementia and gut microbiome-associated metabolites: a cross-sectional study in Japan

Naoki Saji et al. Sci Rep. .

Abstract

Dysregulation of the gut microbiome is associated with dementia. However, the relationship between microbiome-associated metabolites and dementia has yet to be identified. Outpatients visiting a memory clinic in Japan enrolled in this cross-sectional study; 107 subjects were eligible for the study, 25 of which had dementia. We collected demographics, activities of daily living, risk factors, cognitive function, and brain imaging data. The gut microbiome was assessed using terminal restriction fragment length polymorphism analysis. Concentrations of faecal metabolite were measured. We used multivariable logistic regression analyses to identify whether metabolites were independently related to dementia. The concentrations of metabolites were significantly different between subjects with and those without dementia. Every 1 standard deviation increment in faecal ammonia concentration was associated with around a 1.6-fold risk for the presence of dementia. A higher faecal lactic acid concentration was related to a lower risk of dementia, by around 60%. A combination of higher faecal ammonia and lactic acid concentrations was indicative of the presence of dementia, and had a similar predictive value as traditional biomarkers of dementia. Thus, faecal ammonia and lactic acid are related to dementia, independently of the other risk factors for dementia and dysregulation of the gut microbiome.

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Conflict of interest statement

Dr. Saji has received grants from the Grant-in-Aid for Scientific Research (C), JSPS KAKENHI (Grant 20k07861), grants from the NARO Bio-oriented Technology Research Advancement Institution project (Advanced integration research for agriculture and interdisciplinary fields), grants from the Danone Institute of Japan Foundation, grants from the Honjo International Scholarship Foundation, and the BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program. 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. 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). Dr. Murotani, Dr. Hisada, D.r Kunihiro, Mr. Sugimoto, and Ms. Kimura declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Univariable logistic regression analysis of the relationship between standardised metabolite values and the presence of dementia. Dots represent the ORs and lines represent the 95% CI for the presence of dementia.
Figure 2
Figure 2
Logistic regression analysis of standardised (A) ammonia concentration and (B) lactic acid concentration in faecal samples and their relationship with dementia presence. Dots represent the ORs and lines represent the 95% CI for the presence of dementia.
Figure 3
Figure 3
Graphical modelling of all variables. Line thickness is proportional to the number of patients that contributed to the comparison. Green lines indicate a positive relationship, red lines indicate a negative relationship. Abbreviations: amm, standardised faecal ammonia concentration; lct, standardised faecal lactic acid concentration; mns, Mini-Nutritional Assessment-Short Form; bmi, body mass index; sxf, female sex; edu, education year; apo, ApoE ε4 carrier; en1, enterotype I; en3, enterotype III; fb, F/B ratio; vsr, VSRAD score; dmn, the presence of dementia.
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