Relationship Between Plasma Lipopolysaccharides, Gut Microbiota, and Dementia: A Cross-Sectional Study

Article type: Research Article

Authors: Saji, Naoki^{a; *} | Saito, Yoshihiro^b | Yamashita, Tomoya^b | Murotani, Kenta^c | Tsuduki, Tsuyoshi^d | Hisada, Takayoshi^e | Sugimoto, Taiki^{a; f} | Niida, Shumpei^g | Toba, Kenji^h | Sakurai, Takashi^{a; f; i}

Affiliations: [a] Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, Aichi, Japan | [b] Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan | [c] Biostatistics Center, Graduate School of Medicine, Kurume University, Fukuoka, Japan | [d] Laboratory of Food and Biomolecular Science, Department of Bioscience and Biotechnology for Future Bioindustries, Graduate School of Agricultural Science, Tohoku University, Miyagi, Japan | [e] TechnoSuruga Laboratory Co., Ltd., Shizuoka, Japan | [f] Department of Prevention and Care Science, Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan | [g] Research Institute, National Center for Geriatrics and Gerontology, Aichi, Japan | [h] Tokyo Metropolitan Geriatric Medical Center, Tokyo, Japan | [i] Department of Cognition and Behavioral Science, Nagoya University Graduate School of Medicine, Aichi, Japan

Correspondence: [*] Correspondence to: Naoki Saji, MD, PhD, Center for Comprehensive Care and Research on Memory Disorders, National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi 474-8511, Japan. Tel.: +81 562 46 2311; Fax: +81 562 48 2373; E-mail: [email protected].

Abstract: Background:Previous studies have demonstrated associations between gut microbiota, microbial metabolites, and cognitive decline. However, relationships between these factors and lipopolysaccharides (LPS; molecules of the outer membrane of gram-negative bacteria) remain controversial. Objective:To evaluate associations between plasma LPS, gut microbiota, and cognitive function. Methods:We performed a cross-sectional sub-analysis of data of 127 participants (women: 58%, mean age: 76 years) from our prospective cohort study regarding the relationship between gut microbiota and cognitive function. We enrolled patients who visited our memory clinic and assessed demographics, dementia-related risk factors, cognitive function, brain imaging, gut microbiomes, and microbial metabolites. We evaluated relationships between cognitive decline and plasma LPS using multivariable logistic regression analyses. Results:Plasma LPS concentration increased with increasing degree of cognitive decline and total cerebral small vessel disease (SVD) score (Kruskal-Wallis test; p = 0.016 and 0.007, respectively). Participants with high plasma LPS concentrations tended to have lower concentrations of gut microbial metabolites, such as lactic acid and acetic acid, and were less likely to consume fish and shellfish (44.7% versus 69.6%, p = 0.027) than those with low plasma LPS concentrations. Multivariable analyses revealed that plasma LPS concentration was independently associated with the presence of mild cognitive impairment in participants without dementia (odds ratio: 2.09, 95% confidence interval: 1.14–3.84, p = 0.007). Conclusion:In this preliminary study, plasma LPS concentration was associated with both cognitive decline and cerebral SVD and significantly correlated with beneficial gut microbial metabolites. Plasma LPS may be a risk factor for cognitive decline.

Keywords: Biomarkers, cerebral small vessel disease, cognitive decline, dementia, gut microbiota

DOI: 10.3233/JAD-215653

Journal: Journal of Alzheimer's Disease, vol. 86, no. 4, pp. 1947-1957, 2022