Profiling Blautia at high taxonomic resolution reveals correlations with cognitive dysfunction in Chinese children with Down syndrome.

Introduction: Down syndrome (DS), the presence of a supernumerary chromosome 21, is associated with cognitive dysfunction caused by early neurodegenerative processes. Alterations in the gut microbiota were observed in Chinese children with DS, and the genus Blautia was associated with cognitive function in these children. Therefore, it is crucial to understand the detailed composition of this group at the species level and to explore the effect of specific species on cognitive function. Methods: In this study, Blautia-specific amplicon sequencing was conducted to identify the specific Blautia species in 15 children with DS and 15 matched healthy children. Results: The taxonomic analyses suggested that the Blautia taxa were clustered by disease status. The diversity of Blautia at the species level differed between DS patients and healthy controls, with the abundances of Blautia massiliensis and Blautia argi decreasing in DS children, while Blautia faecis was increased. Acetic acid, one of the metabolites of Blautia, was significantly reduced in the DS group. Of particular interest, Kyoto Encyclopaedia of Genes and Genomes analysis revealed decreased modules related to starch and sucrose metabolism and glycolysis. In addition, B. argi was positively related to DS cognitive scores, and B. faecis was negatively related to cognitive function, implying its role on the DS cognitive impairments. Discussion: Our study has important implications for understanding the important effects of specific species of Blautia on cognitive function and thus possibly provides a new strategy for future studies of cognitive improvement in individuals with DS.

Altered gut microbiota correlates with cognitive impairment in Chinese children with Down's syndrome.

Down's syndrome (DS), a common chromosomal disease caused by chromosome 21 trisomy, is the main cause of cognitive impairment in children worldwide. Emerging evidence suggests that the microbiota-gut-brain axis plays a potential role in cognitive impairment. However, data regarding gut microbiota alterations in DS patients remain scarce, especially data from children with DS. This case-control study was conducted to explore the gut microbiota composition in Chinese DS children. Additionally, the potential association between gut microbiota and cognitive function in DS was evaluated. Microbiota communities in the feces of 15 DS subjects and 15 matched controls were investigated using high-throughput Illumina Miseq sequencing targeting the V3-V4 region of 16S rRNA gene. The relationships between gut microbiota composition and DS cognitive function scores were analyzed. The structure and richness of the gut microbiota differed between DS patients and healthy controls. The abundance of Acidaminococcaceae was decreased in DS patients. Moreover, the Kyoto Encyclopedia of Genes and Genomes analysis showed increased modules related to peptidases and pyrimidine metabolism. Overall, we confirmed that gut microbiota alterations occurred in Chinese patients with DS. Additionally, the fecal microbiota was closely related to DS cognitive impairment. Larger cohorts are needed to confirm these findings and to clarify the mechanisms involved. Elucidating these novel findings in the field of microbiota-gut-brain axis will provide a promising strategy for future studies of DS cognitive impairment.

Correlation among gut microbiota, fecal metabolites and autism-like behavior in an adolescent valproic acid-induced rat autism model.

This study aims to understand the relationship between fecal metabolites and gut microbiota in an adolescent valproic acid-induced rat autism model (VPA-exposed offspring). We analyzed the fecal samples of VPA-exposed offspring using 16S rRNA gene sequencing and untargeted metabolomics. Autism-like behavior was evaluated by a three-chamber sociability test and a self-grooming test. Based on these data, we analyzed the association among fecal metabolites, gut microbiota and autism-like behavior. Behavioral tests showed that VPA-exposed offspring displayed typical autism-like behavior. Forty-nine named differential fecal metabolites and 14 enriched KEGG pathways were identified between the VPA and control groups. Five fecal metabolites may be used as characteristic metabolites. The richness and diversity of gut microbiota did not differ between the two groups, while the overall composition of gut microbiota was significantly different. Candidatus_Saccharimonas, Desulfovibrio, [Eubacterium]_xylanophilum_group and Ruminococcus_2 were the characteristic genera of VPA-exposed offspring. Correlation analysis revealed a tight relationship among gut microbiota, fecal metabolites and autistic behavior in VPA-exposed offspring. This study illustrates that specific alterations in gut microbiota and fecal metabolites may be regarded as characteristics of VPA-exposed offspring. The characteristic gut microbiota and fecal metabolites as well as their relationship may play a crucial role in autism-like behavior caused by prenatal exposure to VPA.

Cognitive impairments in adult mice with RIP140 overexpression in neural stem cells.

Receptor-interacting protein 140 (RIP140) is a transcription co-regulator of several transcription factors and a signal transduction regulator. RIP140 was recently implicated in the regulation of cognitive functions. The gene that encodes RIP140 is located on chromosome 21. An increase in RIP140 expression was observed in the fetal cerebral cortex and hippocampus in Down syndrome patients who exhibited strong cognitive disabilities. We hypothesized that RIP140 overexpression affects cognitive function in adult neural development. The present study used a Cre-dependent adeno-associated virus to selectively overexpress RIP140 in neural stem cells using nestin-Cre mice. RIP140 overexpression efficiency was evaluated at the subgranular zone (SGZ) of the dorsal dentate gyrus (dDG) and the subventricular zone (SVZ) of the lateral ventricles (LVs). Mice with RIP140 overexpression in the SGZ exhibited deficits in cognitive function and spatial learning and memory, measured in the Morris water maze, object-place recognition test, and novel object recognition test. However, overexpression of RIP140 in SVZ only impaired performance in the Morris water maze and novel object recognition test but not in the object-place recognition test. Altogether, these results indicated defects in cognitive functions that were associated with RIP140 overexpression in neural stem cells and revealed a behavioral phenotype that may be used as a framework for further investigating the neuropathogenesis of Down syndrome.