Gut microbiota: A new target of traditional Chinese medicine for insomnia.

All species have a physiological need for sleep, and sleep is crucial for the preservation and restoration of many physiological processes in the body. Recent research on the effects of gut microbiota on brain function has produced essential data on the relationship between them. It has been discovered that dysregulation of the gut-brain axis is related to insomnia. Certain metabolites of gut microbiota have been linked to insomnia, and disturbances in gut microbiota can worsen insomnia. Traditional Chinese medicine (TCM) has unique advantages for the treatment of insomnia. Taking the gut microbiota as the target and determining the scientific relevance of TCM to the prevention and treatment of insomnia may lead to new concepts for the treatment of sleep disorders and improve the therapeutic effect of sleep. Taking the gut microbiota as an entry point, this paper reviews the relationship between gut microbiota and TCM, the relationship between gut microbiota and insomnia, the mechanism by which gut microbiota regulate sleep, and the mechanism by which TCM regulates gut microbiota for insomnia prevention and treatment. This review provides new ideas for the prevention and treatment of insomnia through TCM and new ideas for drug development.

Role of Bifidobacterium spp. intake in improving depressive mood and well-being and its link to kynurenine blood level: an interventional study.

OBJECTIVES: Evidence for the contribution of the brain-gut-microbiota axis to the depression pathophysiology is increasing nowadays. Disturbed gut microbiota equilibrium along with bad dietary habits both lead to kynurenine pathway abnormalities contributing to the depression pathophysiology. In this respect, many studies are found but the interventional clinical trials are limited. The present interventional study aims to evaluate the impact of Bifidobacterium spp. supplementation together with improving dietary intake on depressive mood and well-being and their correlation with kynurenine blood level in adult Egyptian healthy volunteers. METHODS: A number of 98 healthy female volunteers with a mean age of 46.96 ± 1.82 years were selected and enrolled in this study. They were given yogurt enriched with Bifidobacterium spp. daily for eight weeks. Clinical examination as well as questionnaires for the evaluation of psychological well-being and depression were done at base line and after eight weeks of intervention. Fasting blood samples and stool samples were collected from all subjects at baseline and eight weeks after the intervention for the investigation of serum kynurenine concentration, blood hemoglobin, serum transaminases (ALT & AST) serum urea and creatinine as well as fecal Bifidobacterium count. RESULTS: Data revealed that both depression and well-being showed highly significant improvement combined with significant drop in kynurenine blood level after intervention. Also, a significant rise in fecal Bifidobacterium count and a significant improvement in hemoglobin level and activity of liver enzymes were recorded. After intervention, a significant negative correlation was recorded between depression and fecal Bifidobacterium count as well as between serum kynurenine level, and well-being. CONCLUSION: Bifidobacterium spp. supplementation combined with improvement in dietary intake resulted in improvement of depressive mood and well-being and reduced kynurenine blood level.

[Effect of electroacupuncture on gut microbiota and serum IL-1ß and IL-18 in rats with vascular dementia based on principle of "curing brain disorders by treating intestines"].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui"(GV20), "Dazhui"(GV14), "Shenshu" (BL23)and "Zusanli"(ST36) on the intestinal flora and serum interleukin (IL)-1ß and IL-18 contents in vascular dementia (VD) rats. METHODS: SD rats were randomized into sham operation, VD model, GV20+GV14+BL23 (EA-basic acupoints), and EA-basic acupoints+ST36 and EA-basic acupoints+probiotics groups (n=10 in each group). EA (10 Hz/50 Hz) was conducted for 30 min, once daily for 4 consecutive weeks. Rats of the EA-basic acupoints+probiotics received gavage of probiotics (2 mL/d containing 2.0×109 CFU of live bifidobacterium), once a day for 4 weeks, and those of the EA-basic acupoints and EA-basic acupoints+ST36 groups received gavage of the same dose of normal saline. The Morris water maze test was used to evalua-te the rats' lear-ning and memory ability before and after the treatment. The serum IL-1ß and IL-18 levels were determined by ELISA, and the histopathological changes of the intestinal mucosa were observed by H.E. staining. The ultrastructural changes of hippocampal neurons were observed by using transmission electron microscopy and 16S rDNA sequencing technique was used to analyze the composition of intestinal microbiome. RESULTS: Compared with the sham operation group, the escape latency, serum levels of IL-1ß and IL-18, as well as the relative abundance of harmful bacteria (including Catabacter, obinsoniella and Desulfovibrio) in the intestine were significantly increased (P<0.01). In comparison with the model group, the escape latency, serum levels of IL-1ß and IL-18 in the three treatment groups, and the relative abundance of harmful bacteria (such as the Catabacter, Robinsoniella and Desulfovibrio) in the EA-basic acupoints+ST36 group were down-regulated obviously(P<0.05,P<0.01), and the relative abundance of Clostridiales-unclassified in both EA-basic acupoints+probiotics and EA-basic acupoints+ST36 groups was significantly up-regulated (P<0.05). The effects of EA-basic acupoints+ST36 and EA-ba-sic acupoints+probiotics were significantly superior to that of EA-basic acupoints in down-regulating IL-18 content (P<0.05). H.E. staining showed atrophy of the whole mucosal layer, loss of goblet cells, destruction of glands, infiltration of a large number of inflammatory cells, and transmission microscope displayed fuzziness of the nucleus membrane boundary, cystic dilation of the rough endoplasmic reticulum with unclear structure swelling of the mitochondria, and disordered arrangement or dissolution of the inner cristae in the model group, which was relatively milder in the EA-basic acupoints+ST36 and EA-basic acupoints+probiotics groups. CONCLUSION: EA of GV20+GV14+BL23+ ST36 can improve the cognitive dysfunction of VD model rats, which may be related to its function in regulating the imbalance of intestinal microbiota, thereby inhibiting the peripheral inflammatory factor.

Poria cocos could ameliorate cognitive dysfunction in APP/PS1 mice by restoring imbalance of Aß production and clearance and gut microbiota dysbiosis.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid beta-protein (Aß) plaques, which are the hallmark of AD, are formed from the imbalance of Aß production and clearance accompanied by neuroinflammation, gut dysbiosis, and metabolite dysfunction. All of these processes give rise to neurochemical deficiencies and synaptic dysfunction, which ultimately contribute to recognition dysfunction. Poria cocos (PC), which contains multiple active ingredients, plays a significant role in the treatment of multiple-pathogenesis senile diseases such as AD. Nevertheless, there are only very few investigations on the intricate action mechanism of PC for the treatment of AD. In this study, we evaluate the multi-target cure effect of PC on APP/PS1 mice by behavioral, immunohistochemical (IHC), targeted metabolomics, and 16S rRNA sequencing experiments. Mice treated with PC showed significant improvements in cognitive function as evaluated by the behavioral experiment. IHC revealed that PC treatment relieved Aß deposition by reducing the formation of Aß and increasing its clearance. Moreover, PC treatment improved gut dysbiosis, which reversed the metabolite dysfunction of bile acid. These findings reveal that PC is a promising therapeutic agent, which might ameliorate the cognitive function of AD by restoring the imbalance of Aß production and clearance and gut microbiota dysbiosis.

Brain-gut-microbiota axis in Parkinson's disease.

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.