Gut Microbiota and Targeted Biomarkers Analysis in Patients With Cognitive Impairment

 What EXACTLY is your doctor doing to ensure your correct gut microbiota? Doing nothing? Then that is a fireable offense, along with firing the board of directors for incompetence.

Gut Microbiota and Targeted Biomarkers Analysis in Patients With Cognitive Impairment

Shourong Lu¹, Ying Yang¹, Qiao Xu¹, Shuqiang Wang², Jie Yu¹, Bingshan Zhang¹, Zhuo Wang¹, Yunyun Zhang^3*, Wenwei Lu^4* and Kan Hong^1*

• ¹Department of Geriatric, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
• ²Department of Medicine, Wuxi Xin'an Community Health Service Center, Wuxi, China
• ³Department of General Practice, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
• ⁴State Key Laboratory of Food Science and Technology and School of Food Science and Technology, Jiangnan University, Wuxi, China

Gut microbial alteration is closely associated with brain disorders including cognitive impairment (CI). Gut microbes have the potential to predicate the development of diseases. However, the gut microbial markers for CI remain to be elucidated. In this study, the gut microbial alterations were assessed using16S rRNA sequencing, and identified the gut microbial markers using a random forest model. The results showed that there were significant gut microbial differences between the control and CI groups based on beta diversity (p < 0.002). Patients with CI had higher abundances of Actinobacteria and Proteobacteria but lower proportions of Bcateroidetes and Firmicutes vs. that in the control group. Patients had 39 special genera and the control subjects had 11 special genera. Furthermore, 11 genera such as Blautia, Roseburia, and Lactococcus and 18 genera such as Lactobacillus, Ruminococcus 2, and Akkermansia were the differential taxa in the control and CI groups, respectively. Gene functions related to nutrient metabolisms were upregulated in patients with CI. This suggested that the huge differences in gut microbes between the two groups and gut microbiota had the potential to predicate the development of CI. Based on machine learning results, 15 genera such as Lactobacillus, Bifidobacterium, and Akkermansia were selected as the optimal marker set to predicate CI with an area under curve (AUC) value of 78.4%. The results revealed the gut microbial markers for CI and provided a potential diagnosis tool to prevent the development of CI in the elderly.

Introduction

Cognitive impairment is closely associated with the development of psychiatric illnesses such as hypertension, depression, and Alzheimer's disease (1–3). Age is an important factor for cognitive impairment (CI) and there is increasing prevalence with the development of aging worldwide (4). Furthermore, educational degree, sleep disorder, and vitamin D intake are the risk factors for CI in elderly people (5–7). In the elderly, gastrointestinal tract and brain functions are gradually declining, and these factors are inevitable challenges for them. CI is the high-risk factor for dementia in elderly people, 10–30% of patients with mild CI and 20–66% of them convert into dementia within 1 and 2–4 years, respectively (8, 9). Dementia is difficult to reverse and there are no effective ways to treat it (10). CI leads to a huge burden for family and society. Therefore, the early prevention of CI is a key window to reduce the prevalence of dementia in the elderly.

Gut microbial alteration is closely associated with the development of aging in the elderly and affects their physiology functions including CI. The “Gut-brain” axis has been reported to solve the function barrier related to the brain and suggests bacteria play a key role in the development of neurodevelopmental disorders (11). Bacterial species such as Limosilactobacillus reuteri, Bifidobacterium pseudolongum, and Lactobacillus johnsonii are reduced in the maternal high-fat-diet offspring and negatively affect offspring social behavior (12). Verrucomicrobiaceae and unclassified Firmicutes are increased but Prevotellaceae and Erysipelotrichaceae are decreased, and they affect the β-glucuronate and tryptophan metabolism in the patients with Parkinson's disease (13). These results suggest that gut microbiota and their metabolism influence deeply the brain function and manipulate the host's emotion and behavioral intentions. Fecal microbiota transplant from aged donor mice into young recipients leads to impaired spatial learning and memory (14). This implies that gut microbiota is an important cause to induce CI symptoms.

In recent years, microbial marker severs as a non-invasive diagnosis tool for some diseases such as hepatocellular carcinoma, colorectal cancer, and type 2 diabetes (15–17). Gut microbial marker has the potential to predict the development of CI and may be an effective target tool to prevent CI in the elderly. In this study, a total of 60 fecal samples were collected from the patients with CI and control subjects. Combined 16S rRNA sequencing with machine learning revealed microbial biomarkers that predicted the development of CI and provided a potential diagnosis tool to prevent CI for the elderly.

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