A common symptom in Alzheimer’s disease (AD) is cognitive decline, of which the potential pathogenesis remains unclear. In order to understand the mechanism of gut microbiota in AD, it is necessary to clarify the relationship between gut microbiota and metabolites. Behavioral tests, pathological examination, metagenomics, and metabolomics were applied to analyze the difference of gut microbiota and metabolome between APPswe/PS1ΔE9 (PAP) mice with cognitive decline and age-matched controls, and their possible correlations. Our results showed that PAP mice and health mice had different structures of the bacterial communities in the gut. The abundances and diversities of the bacterial communities in health mice were higher than in PAP mice by metagenomics analysis. The abundances of Libanicoccus massiliensis, Paraprevotella clara, and Lactobacillus amylovorus were significantly increased in PAP mice, while the abundances of Turicibacter sanguinis, Dubosiella newyorkensis, and Prevotella oris were greatly reduced. Furthermore, PAP mice possessed peculiar metabolic phenotypes in stool, serum, and hippocampus relative to WT mice, as is demonstrated by alterations in neurotransmitters metabolism, lipid metabolism, aromatic amino acids metabolism, energy metabolism, vitamin digestion and absorption, and bile metabolism. Microbiota–host metabolic correlation analysis suggests that abnormal metabolism in stool, serum, and hippocampus of PAP mice may be modulated by the gut microbiota, especially T. sanguinis, D. newyorkensis, and P. oris. Therefore, abnormal metabolism activity is associated with gut microbiota in Alzheimer’s disease mice. Our results imply that modifying host metabolism through targeting gut microbiota may be a novel and viable strategy for the prevention and treatment of AD in the future.

A gram-positive, facultatively anaerobic, and coccoid or ovoid-shaped bacterium designated M2458 T was isolated from the intestinal contents of APP swe /PS ΔE9 mouse model of Alzheimer's disease. With the polyphasic approach, the taxonomic position of the novel isolate was con rmed. Strain M2458 T grew well at 37°C on YCFA agar. Strain M2458 T belongs to the family Streptococcaceae and class Bacilli, and it is related to Lactococcus formosensis NBRC 109475 T (97.59% sequence similarity) according to its 16S rRNA gene sequence. In a comparison of two housekeeping genes, rpoA and rpoB, strain M2458 T was found to be well separated from Lactococcus formosensis NBRC 109475 T . On the basis of whole genome sequences, the DNA G + C content was 38.29 mol%. In terms of average nucleotide identity and digital DNA-DNA hybridization, strain M2458 T was identi ed as a novel species of the genus Lacococcus. The major fatty acids (> 10% of the total fatty acids) were C18:1ω9c (39.68%), C16:0 (13.26%) and C18:1ω7c (11.52%). The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and an unidenti ed phospholipid. As a result of its genotypic and phenotypic characteristics, strain M2458 T was considered to be a new species within the genus Lactococcus; the name Lactococcus intestinalis sp. nov. has been proposed, with type strain M2458 T (= JCM 35706 = CGMCC 1.60066).

A Gram˗stain˗negative, anaerobic, non˗motile, non˗spore˗forming, rod˗shaped bacterial strain named as NGMCC 1.200684T was isolated from the fresh feces of rhinoceros in Beijing Zoo. Based on 16S rRNA gene sequences, phylogenetic analysis indicated that strain NGMCC 1.200684T belonged to the genus Bacteroides and was most strongly related to the type strain of Bacteroides uniformis ATCC 8492T (96.88%). The G+C content of the genomic DNA was determined to be 46.62 mol%. Between strains NGMCC 1.200684T and Bacteroides uniformis ATCC 8492T, the average nucleotide identity (ANI) and digital DNA˗DNA hybridization (dDDH) were 93.89 and 67.60%, respectively. Strain NGMCC 1.200684T can produce acid from fermentation of several substrates, including glucose, mannitol, lactose, saccharose, maltose, salicin, xylose, cellobiose, mannose, raffinose, sorbitol, trehalose, D˗galactose，maltotriose. The major cellular fatty acids (>10 %) were identified as anteiso˗C15:0, iso˗C15:0, iso˗C14:0, iso˗C17:0 3˗OH. The polar lipid profile of strain NGMCC 1.200684T was determined to contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unknown phospholipids, two unknown aminophospholipids. Based on phenotypic, phylogenetic and chemotaxonomic characteristics, a novel species of the genus Bacteroides, Bacteroides rhinocerotis sp. nov. is proposed. The type strain is NGMCC 1.200684T (=CGMCC 1.18013T=JCM 35702T).