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Acupuncture Can Play an Antidepressant Role by Regulating the Intestinal Microbes and Neurotransmitters in a Rat Model of Depression.
BACKGROUND Acupuncture, which has many good effects and few adverse effects, is widely recognized as an alternative therapy for depression in clinical practice. This study aimed to explore the mechanism of acupuncture in antidepressant treatment. MATERIAL AND METHODS In this experiment, Sprague-Dawley rats were randomly divided into 4 groups: control, chronic unpredictable mild stress (CUMS), acupuncture, and fluoxetine groups. The CUMS, acupuncture, and fluoxetine groups were orphaned and subjected to chronic unpredictable stress for 6 weeks, and the acupuncture and fluoxetine groups were treated with their respective intervention in weeks 4-6. The body weight of rats was monitored weekly. After behavioral tests were completed, serum, feces, and hippocampal tissue of rats were collected. RESULTS The results showed that the acupuncture and fluoxetine treatments could alleviate the behavioral changes caused by CUMS. The treatments increased the total distance of rat crossing in the open-field test, prolonged the activity time of the open cross maze in the open arm, and improved the rate of sucrose consumption in the sucrose preference test. In addition, both the decreased level of dopamine (DA) and 5-hydroxytryptamine (5-HT) in serum and hippocampus caused by CUMS were improved after the treatments with acupuncture and fluoxetine, and the decreased expression of brain-derived neurotrophic factor signaling and the astrocytes in the hippocampus caused by CUMS were increased after the treatments with acupuncture and fluoxetine. Acupuncture and fluoxetine also decreased the ß isoform of calmodulin-dependent protein kinase II in the hippocampus, which was increased by CUMS. Furthermore, acupuncture regulated intestinal microbial disorders caused by CUMS, which reduced the relative abundance ratio of Bacteroidetes/Firmicutes in rats. CONCLUSIONS Our experimental results indicate that acupuncture can alleviate depression-like performance in CUMS rats by regulating intestinal microbes and neurotransmitters.
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Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model.
Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.
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Correlation between Intestinal Flora and Serum Inflammatory Factors in Post-stroke Depression in Ischemic Stroke.
OBJECTIVE: To investigate the correlation between intestinal flora and serum inflammatory factors IL-1, IL-2, IL-6 and hs-CRP in post-stroke depression (PSD) in ischemic stroke patients. STUDY DESIGN: Observational study. Study Place and Duration of Study: Jiulongpo District Hospital of Traditional Chinese Medicine, Chongqing City, China, from October 2018 to May 2020. METHODOLOGY: One hundred and sixty-three patients with ischemic stroke were divided into Group A (PSD) and Group B (no PSD), according to whether they had PSD. Intestinal flora indexes (Enterococcus faecalis, Escherichia coli and Bifidobacterium) and serum IL-1, IL-2, IL-6 and hs-CRP were detected. RESULTS: Among 163 patients with ischemic stroke, 67 (41.10%) had PSD (Group A) and 96 (58.90%) had no PSD (Group B). Contents of Enterococcus faecalis and Escherichia coli in Group A were higher than those in Group B (both p <0.001), and content of Bifidobacterium in Group A was lower than that in Group B (p <0.001). Serum IL-1, IL-2, IL-6 and hs-CRP levels in Group A were higher than those in Group B (all p <0.001). Pearson correlation test showed that contents of Enterococcus faecalis and Escherichia coli in Group A were positively correlated with IL-1, IL-2, IL-6 and hs-CRP, and content of Bifidobacterium was negatively correlated with IL-1, IL-2, IL-6 and hs-CRP. CONCLUSION: There are intestinal flora imbalance and Bifidobacterium undergrowth in patients with PSD, which can lead to overexpression of serum inflammatory factors. Both may be involved in occurrence and progress of PSD in patients with ischemic stroke. Key Words: Ischemic stroke, Post-stroke depression (PSD), Intestinal flora, Inflammatory factors.
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Perinatal depression: Heterogeneity of disease and in animal models.
Perinatal depression (PND) can have either an antepartum or postpartum onset. Although the greatest risk factor for PND is previous depression history,de novoPND occurs with the majority of cases occurring in the postpartum. Timing of depression can impact etiology, prognosis, and response to treatment. Thus, it is crucial to study the impact of the heterogeneity of PND for better health outcomes. In this review, we outline the differences between antepartum and postpartum depression onset of PND. We discuss maternal physiological changes that differ between pregnancy and postpartum and how these may differentially impact depression susceptibility. We highlight changes in the maternal steroid and peptide hormone levels, immune signalling, serotonergic tone, metabolic factors, brain morphology, and the gut microbiome. Finally, we argue that studying the heterogeneity of PND in clinical and preclinical models can lead to improved knowledge of disease etiopathology and treatment outcomes.
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Gut-Brain Axis: Role of Microbiome, Metabolomics, Hormones, and Stress in Mental Health Disorders.
The influence of gut microbiome, metabolites, omics, hormones, and stress on general and mental health is increasingly being recognized. Ancient cultures recognized the importance of diet and gut health on the overall health of an individual. Western science and modern scientific methods are beginning to unravel the foundations and mechanisms behind some of the ancient beliefs and customs. The gut microbiome, an organ itself, is now thought to influence almost all other organs, ranging from the brain to the reproductive systems. Gut microbiome, metabolites, hormones, and biological sex also influence a myriad of health conditions that range from mental health disorders, obesity, gastrointestinal disorders, and cardiovascular diseases to reproductive health. Here, we review the history and current understanding of the gut-brain axis bidirectional talk in various mental health disorders with special emphasis on anxiety and depressive disorders, whose prevalence has increased by over 50% in the past three decades with COVID-19 pandemic being the biggest risk factor in the last few years. The vagal nerve is an important contributor to this bidirectional talk, but other pathways also contribute, and most remain understudied. Probiotics containing Lactobacillus and Bifidobacterium species seem to have the most impact on improvement in mental health symptoms, but the challenge appears to be maintaining sustained levels, especially since neither Lactobacillus nor Bifidobacterium can permanently colonize the gut. Ancient endogenous retroviral DNA in the human genome is also linked to several psychiatric disorders, including depression. These discoveries reveal the complex and intricately intertwined nature of gut health with mental health disorders.
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Relationship Between the Fecal Microbiota and Depression and Anxiety in Pediatric Patients With Orthostatic Intolerance.
OBJECTIVE: Orthostatic intolerance (OI) is an important health problem for children and adolescents. The onset and exacerbation of OI are strongly affected by psychosocial factors. Intestinal microbial deviations, which are affected by food and lifestyle factors, are an important risk factor for adult psychiatry patients, but their roles in pediatric patients are unclear. The objective of this study was to investigate the intestinal microbiota and its involvement in the mental health of children with OI. METHODS: Fifty-six fecal samples from pediatric OI patients and 9 samples from healthy children were examined with terminal-restriction fragment length polymorphism analysis from July 2016 to January 2018 at Nihon University Itabashi Hospital, Tokyo, Japan. Bacterial diversity was analyzed using the Shannon-Wiener index and the Simpson index. All OI patients were assessed using 2 different psychological scales: the Children's Depression Inventory and the Children's Manifest Anxiety Scale. The patients were then divided into the following subgroups: depression or nondepression and anxiety or nonanxiety. RESULTS: The mean proportion of Clostridium subcluster XIVa and/or Enterobacteriaceae (operational taxonomic unit [OTU] 940) in the OI patients was significantly higher than that in the healthy controls (P = .02). Among OI patients, Bifidobacterium (OTU 124) was less frequent in the depression group than in the nondepression group. However, depression and anxiety showed no correlation with bacterial diversity. CONCLUSIONS: Pediatric OI patients showed deviations in the intestinal bacterial flora. The intestinal flora can serve as a novel therapeutic target for the mental health management of intractable pediatric OI patients.
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Association of dietary intake of live microbes with bowel health and depression in US adults: a cross-sectional study of NHANES 2005-2010.
BACKGROUND: Depression substantially impacts on quality of life, personal relationships, and self-care. Gastrointestinal disorders are the common comorbidity of depression and 24.3% of patients with depression have disordered bowel habits. Dietary intake of live microbes alters the host's microflora and is beneficial for the prevention and control of bowel health and depression. We aim to investigate the association of dietary intake of live microbes with bowel health and depression and to further examine weather bowel health or depression mediates the therapeutic effect of live microbes. METHODS: Participants' data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, which is designed to examine the health and nutritional status of the non-institutionalized US population by a complex, multi-stage, probability sampling design. The foods were grouped into categories on the basis of estimated microbial levels: low (<104 CFUs/g), medium (Med; 104-107 CFU/g), and high (Hi; >107 CFU/g). Participants were further classified into three groups (G1: participants without MedHi foods intakes; G2: those with MedHi foods intakes greater than zero but less than the median; and G3: those with MedHi foods intakes greater than the median). RESULTS: A total of 10,785 US adults were selected. The median of MedHi foods intake was 66.1 g/day. Participants in the G2 (OR = 0.739, 95% CI: 0.581-0.941) and G3 (OR = 0.716, 95% CI: 0.585-0.877) groups had significant association with lower risks of depression, and participants in the G3 group had significant association with lower risks of hard stools (OR = 0.885, 95% CI: 0.692-0.989) and loose stools (OR = 0.769, 95% CI: 0.585-0.954). Interestingly, further mediation analyses showed that the association of dietary live microbe intake with depression is mediated by the stool types, and the association of dietary live microbe intake with stool types is mediated by the depression (all P < 0.05). CONCLUSIONS: A high dietary intake of live microbes, especially a minimum of 66.1 g of MedHi foods per day, is associated with a lower risk of depression, hard stools, and loose stools consistency. Depression and bowel health mutually act as mediators in this association, indicating dietary intake of live microbes may simultaneously affect bowel health and depression.
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[Effect of umbilical moxibustion on intestinal flora in patients with subthreshold depression].
OBJECTIVE: To observe the clinical efficacy of umbilical moxibustion for subthreshold depression (SD) and its effect on intestinal flora, and to explore its mechanism. METHODS: Thirty-six SD patients were recruited as the SD group (1 case dropped out, 2 cases excluded), and 36 healthy subjects were recruited as the healthy control group (1 case excluded). The SD group was treated with umbilical moxibustion, once a week, a total of 8 times were required. The healthy control group did not receive any intervention. Hamilton depression scale 17-item (HAMD-17) and Center for Epidemiologic Studies depression scale (CES-D) scores were observed in the SD group before and after treatment, and the clinical efficacy was evaluated. Fecal samples were collected in the SD group before and after treatment and in the healthy control group when enrolled, the intestinal flora was analyzed by 16S rRNA sequencing technology. RESULTS: The HAMD-17 and CES-D scores after treatment in the SD group were reduced compared with those before treatment (P<0.05), and the total effective rate was 90.9% (30/33). Compared with the healthy control group, Sobs index, Shannon index and Ace index were reduced in the SD group before treatment (P<0.05), Simpson index was increased (P<0.05), the relative abundance of Escherichia-Shigella was increased (P<0.01), the relative abundance of Eubacterium_hallii_group, Ruminococcus, Christensenellaceae_R-7_ group, Paraprevotella was decreased (P<0.05, P<0.01). Compared before treatment, the relative abundance of Escherichia- Shigella after treatment in the SD group was decreased (P<0.01), the relative abundance of Ruminococcus, Christensenaceae_R-7_group, Paraprevotella was increased (P<0.01, P<0.05). Christensenellaceae_R-7_group and Paraprevotella were negatively correlated with the CES-D score (P<0.01, P<0.05). Escherichia-Shigella was positively correlated with the HAMD-17 score (P<0.05). Christensenellaceae_R-7_group was negatively correlated with the HAMD-17 score (P<0.01). CONCLUSION: Patients with subthreshold depression have dysbiosis of intestinal flora, and umbilical moxibustion may exert therapeutic effect by regulating the abundance and diversity of intestinal flora, increasing beneficial bacteria, and reducing harmful bacteria.
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The Gut Microbiome and Mental Health.
The gut microbiome has been well researched in the past few years and may be a target for treating mental illness. Trillions of bacteria in the digestive system work with the brain, immune function, and endocrine pathways. This gut microbiome ecosystem mediates the interaction between the human being and the environment making its inclusion in holistic nursing essential. Changes in normal balance of the gut microbiome occur with diet, antibiotics and other medications, stress, cancer treatment, geography and environment, and current illnesses. When the microbiome is challenged a "dysbiotic" state leads to inadequate production of needed neurotransmitters such as serotonin and dopamine. Research has shown links between the dysbiosis, and the inflammatory response system that are known to contribute to depression, anxiety, and schizophrenia. Understanding the role of the gut microbiome can be beneficial to holistic nurses, providing a new tool to prevent, treat, or reduce symptoms of mental illness and improve general immune function. This innocuous holistic approach to mental wellness is becoming an important evidenced-based approach.
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[Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].
BACKGROUND: The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. METHOD: Overview RESULTS AND CONCLUSIONS: Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.