Identification of Gut Microbiome Signatures in Patients With Post-stroke Cognitive Impairment and Affective Disorder

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Identification of Gut Microbiome Signatures in Patients With Post-stroke Cognitive Impairment and Affective Disorder

Yinting Huang^†, Zibin Shen^† and Wenzhen He^*

• Department of Neurology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China

Stroke (ST), endangering human health due to its high incidence and high mortality, is a global public health problem. There is increasing evidence that there is a link between the gut microbiota (GM) and neuropsychiatric diseases. We aimed to find the GM of ST, post-ST cognitive impairment (PSCI), and post-ST affective disorder (PSTD). GM composition was analyzed, followed by GM identification. Alpha diversity estimation showed microbiota diversity in ST patients. Beta diversity analysis showed that the bacterial community structure segregated differently between different groups. At the genus level, ST patients had a significantly higher proportion of Enterococcus and lower content of Bacteroides, Escherichia-Shigella, and Megamonas. PSCI patients had a significantly higher content of Enterococcus, Bacteroides, and Escherichia-Shigella and a lower proportion of Faecalibacterium compared with patients with ST. Patients with PSTD had a significantly higher content of Bacteroides and Escherichia-Shigella and lower content of Enterococcus and Faecalibacterium. Parabacteroides and Lachnospiraceae were associated with Montreal cognitive assessment score of ST patients. Our study indicated that the characteristic GM, especially Bacteroidetes, could be used as clinical biomarkers of PSCI and PSTD.

Introduction

Stroke (ST) is the leading cause of death worldwide (Bonita et al., 2004). It can cause some neuropsychiatric diseases, including anxiety, depression, fatigue, apathy, personality changes, mania, and cognitive impairment. It is estimated that 1/3 of ST patients will develop neuropsychiatric disorders shortly after ST (Hackett and Pickles, 2014; Hackett et al., 2014). Post-ST cognitive impairment (PSCI) and post-ST affective disorder (PSTD) are the common complications of ST. The prevalence of depression and cognitive impairment within 3 months after ST are 25–31% and 10–47.3%, respectively (Aström et al., 1993; Jacquin et al., 2014). These two diseases usually coexist in ST patients and have a negative impact on the prognosis of the patient. Cognitive dysfunction is closely related to depression and interacts. Previous studies have shown that the cognitive function of ST patients after antidepressant treatment is normal, and vice versa, which suggest that they may have similar causes. In clinical practice, the limited use of scales and the inability to detect early symptoms have led to the failure of some patients with PSCI to receive correct diagnosis and treatment. Therefore, early evaluation and treatment of PSCI are important to prolong survival time after ST.

Gut microbiota (GM) disorders in neuropsychiatric diseases have been found in some studies (Bains et al., 2019; Nguyen et al., 2019). Recent studies have shown that there are significant differences in fecal microbial diversity in patients with Alzheimer's disease (AD) (Zhuang et al., 2018). Jiang et al. found that the gut microbial structure of patients with active–severe depression has changed, among which, Bacteroidetes, Proteobacteria, Actinobacteria, and Enterobacteriaceae significantly increased, Firmicutes and Faecalibacterium decreased significantly (Jiang et al., 2015). The reduced proportion of Faecalibacterium leads to chronic low-grade inflammation of the intestinal blood–brain barrier, and is negatively related to the severity of depressive symptoms (Jiang et al., 2015). Recent studies have shown that compared with healthy controls, the composition of the intestinal flora of AD patients has changed (Liu et al., 2019). These reports suggest that the GM may be a crucial regulator of two-way communication between the gut and the brain.

More and more evidence show that intestinal flora can be used as a non-invasive diagnostic biomarker for schizophrenia and type 2 diabetes. It is worth noting that ST patients show obvious intestinal floral imbalance (characterized by a higher abundance of conditional pathogenic bacteria and a lower level of beneficial bacteria). In addition, in patients with PSCI, the abundance of Fusobacteria increases and short-chain fatty acids (SCFAs) decrease. However, the composition of the GM in PSCI and PSTD patients has not been evaluated. Therefore, the discovery of the characteristics of the gut microbial composition of PSCI and PSTD patients is of great significance for rehabilitation after ST. Herein, we aimed to investigate the GM composition in ST, PSCI, and PSTD patients. Besides, we also confirmed the characteristic GM of PSCI and PSTD and its potential as a biomarker for the diagnosis of the disease.