TY - JOUR
T1 - Relationship between dementia and gut microbiome-associated metabolites
T2 - a cross-sectional study in Japan
AU - Saji, Naoki
AU - Murotani, Kenta
AU - Hisada, Takayoshi
AU - Kunihiro, Tadao
AU - Tsuduki, Tsuyoshi
AU - Sugimoto, Taiki
AU - Kimura, Ai
AU - Niida, Shumpei
AU - Toba, Kenji
AU - Sakurai, Takashi
N1 - Funding Information:
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.
Funding Information:
This study was supported by research grants from the Research Funding of Longevity Sciences (26–20, 27–21, 28–15, 30–1, 19–24), the National Center for Geriatrics and Gerontology, grants from the NARO Bio-oriented Technology Research Advancement Institution project (Advanced integration research for agriculture and interdisciplinary fields), grants from the Grant-in-Aid for Scientific Research (C), JSPS KAKENHI (Grant 20k07861), grants from the Danone Institute of Japan Foundation, and grants from the Honjo International Scholarship Foundation. We would like to thank Maki Yamamoto, Yukie Ohsaki, Saori Yoshimura, Hana Saito, Ayaka Suzuki (NCGG), and Yuya Shinkawa (Kurume University) for their technical and secretarial assistance, and the BioBank, NCGG, for the quality control of the clinical samples and data. We thank Dr. Nia Cason, Dr. Karyn Heavner, and Dr. Bronwen Gardner from Edanz Group (www.edanzediting.com/ac) for editing drafts of this manuscript.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-020-65196-6
DO - 10.1038/s41598-020-65196-6
M3 - Article
C2 - 32424166
AN - SCOPUS:85084903278
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 8088
ER -