MCI has important implications for the health of the elderly, since those with history of MCI are more likely to develop AD in the long term [13, 14]. A number of studies have provided compelling evidence that dysbiosis plays an important role in the pathogenesis of AD and many other neurodegenerative diseases . However, the research on gut microbiome exposed to MCI is limited. In the present study, we initiatively examined the gut dysbiosis in MCI cases.
In our results, the relationship between bacterial taxonomic profile and MCI was not characterized by altered α-diversity. But a separation between MCI and control groups can be visualized in β-diversity analysis, suggesting abnormal depletion of certain bacterial taxa. In particular, the reduction of Bacteroides salyersiae and Bacteroides gallinarum in MCI cases was in line with previous research on AD. Zhuang et al. reported depletion of Bacteroides genus in AD but could not specify the depleted species by conventional 16S rRNA sequencing . In fact, Bacteroides fragilis, another species of Bacteroides genus was reported to be decreased in patients with cognitive impairment and brain amyloidosis . Our finding further corroborated the relevance of Bacteroides genus in gut microbiota to neurodegenerative diseases and provided 2 more species, which can be used as potential biomarkers for early detection of MCI/AD risks .
On the other hand, the enrichment of certain taxa in MCI subjects were also found to be related to neurodegeneration. For example, Staphylococcus intermedius and Staphylococcus lentus of Staphylococcus genus exhibited significantly higher abundance in MCI group than in control group.
A series of studies have suggested that Staphylococcus are involved in the generation of extracellular amyloid fibers  through multiple mechanisms, including regulation of phenol soluble modulins (PSMs). PSMs produced by Staphylococcus have been documented to form amyloid fibers in biofilms . While most published evidence pointed to the relevance of Staphylococcus aureus, our results identified two other species in the same genus, thus expanding the scope of investigating the role played by in Staphylococcus in neurodegeneration.
Our study is notable for certain technique advantages. First, among numerous studies on Alzheimer’s disease, the present research initiatively investigated MCI as a separate phenotype, thus providing unique insights into the progression from MCI to AD. Second, unlike 16S rRNA sequencing that only provide genus-level data , the 16S quantitative microarray technology enabled us to scrutinize MCI-related alterations in gut microbiome at species level. This benefic would not only shed light on the role played by brain-gut axis in the process of neurodegeneration, but also promote the development of more precise diagnostic methods for MCI based on gut microbiota signatures.
In the meantime, several limitations of our results should be taken into consideration. For example, due to the complex process of participant enrollment and strict exclusion criteria, the size of our sample was restricted. The relatively low sample size does not allow to exclude the β-error when statistical significance is not reached. This could partially explain the discovery of some differentially abundant taxa in our MCI samples but not in previously published results on AD patients. In addition, since all the participants were recruited from the same hospital, potential regional variations of gut microbiota could not be evaluated. Our further study is aimed at a multi-center clinical research with larger the sample size to thoroughly investigate the gut microbiota among MCI subjects across different regions.
In conclusion, the present study provided new evidence on the abnormalities of gut microbiota in mild cognitive impairment cases as compared to controls subjects. Our results can guide the development of microbiota-based diagnosis for detecting early risks of mild cognitive impairment and subsequent Alzheimer’s disease. And the newfound bacteria with alterations in mild cognitive impairment may provide clues for probiotics regimen that alleviate age-associated cognitive decline.