Altered Gut Microbiota in Adults with Subjective Cognitive Decline: The SILCODE Study

Article type: Research Article

Authors: Sheng, Can^{a; *} | Lin, Li^a | Lin, Hua^a | Wang, Xiaoni^{a; *} | Han, Ying^{a; b; c; *} | Liu, Shu-Lin^{d; e; f; g}

Affiliations: [a] Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing, China | [b] School of Biomedical Engineering, Hainan University, Haikou, China | [c] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, China | [d] Genomics Research Center, State-Province Key Laboratories of Biomedicine Pharmaceutics of China, College of Pharmacy, Harbin Medical University, Harbin, China | [e] HMU-UCCSM Centre for Infection and Genomics, Harbin, China | [f] Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China | [g] Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada

Correspondence: [*] Correspondence to: Ying Han, MD, PhD, Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Tel.: +86 18515692701; Fax: +86 10 83167306; E-mail: [email protected]; Xiaoni Wang, PhD, Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Tel.: +86 15010546586; E-mail: [email protected]; Can Sheng, PhD, Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China. Tel.: +86 18701257298; E-mail: [email protected].

Abstract: Background:Subjective cognitive decline (SCD) is the earliest symptomatic manifestation of preclinical Alzheimer’s disease (AD). Gut microbiota may serve as a susceptibility factor for AD. Altered gut microbiota has been reported in patients with mild cognitive impairment (MCI) and AD dementia. However, whether gut microbial compositions changed in SCD remains largely unknown. Objective:To characterize the gut microbiota in SCD. Methods:In this study, a total of 105 participants including 38 normal controls (NC), 53 individuals with SCD, and 14 patients with cognitive impairment (CI) were recruited. Gut microbiota of all participants isolated from fecal samples were investigated using 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. The gut microbial compositions were compared among the three groups, and the association between altered gut microbiota and cognitive performance was analyzed. To validate the alteration of gut microbiota in SCD, we conducted amyloid positron emission tomography (PET) in selected participants and further compared the gut microbiota among subgroups. Results:The abundance of phylum Firmicutes, class Clostridia, order Clostridiales, family Ruminococcaceae, and genus Faecalibacterium showed a trend toward a progressive decline from NC to SCD and CI. Specifically, the abundance of the anti-inflammatory genus Faecalibacterium was significantly decreased in SCD compared with NC. In addition, altered bacterial taxa among the three groups were associated with cognitive performance. The findings were validated in SCD participants with positive amyloid evidence. Conclusion:The composition of gut microbiota is altered in individuals with SCD. This preliminary study will provide novel insights into the pathophysiological mechanism of AD.

Keywords: Alzheimer’s disease, gut microbiota, 16S ribosomal RNA, subjective cognitive decline

DOI: 10.3233/JAD-210259

Journal: Journal of Alzheimer's Disease, vol. 82, no. 2, pp. 513-526, 2021