No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Long-term Pu-erh tea consumption improves blue light-induced depression-like behaviors
Abstract
Blue light emitted by smartphones and tablets at night increases the risk of depression. Pu-erh tea has been reported to reduce the risk of depression by regulating tryptophan metabolism, but its underlying protective mechanism on depression induced by blue light at night (BLAN) remains unclear. In this work, two groups of C57BL6/J mice were given water or 0.25% (w/v) Pu-erh tea for 120 days, followed by a 45-day BLAN treatment (400 lux blue light between 21:00 and 23:00) to simulate blue light emitted from electronic equipment. Our results indicated that BLAN induced depression-like behaviors and gut microbiota disorders in healthy mice. Pu-erh tea intake significantly reshaped the gut microbiome (especially Bifidobacterium) and regulated the metabolism of short-chain fatty acids (SCFAs) which protected the integrity of the intestinal barrier. This improvement further reduced blood-brain barrier (BBB) damage and alleviated neuroinflammation by inhibiting MyD88/NF-κB pathways which finally regulated neurotransmitters such as brain-derived neurotrophic factor (BDNF) and serotonin (5-hydroxytryptamine, 5-HT). Collectively, 0.25% (w/v) Pu-erh tea has the potential to prevent BLAN-induced depression-like behaviors by reshaping the gut microbiota and increasing the generation of SCFAs via the gut-brain axis.
... Additionally, the intake of Pu-erh tea significantly modulated the gut microbiome, particularly enhancing the Bifidobacterium population, and regulated the metabolism of SCFAs. This beneficial change contributed to reducing blood-brain barrier damage and alleviating neuroinflammation associated with depression-like behaviors by inhibiting the MyD88/NF-κB pathways [80]. ...
Tea, derived from the young leaves and buds of the Camellia sinensis plant, is a popular beverage that may influence the host microbiota. Its consumption has been shown to promote the growth of beneficial bacterial species while suppressing harmful ones. Simultaneously, host bacteria metabolize tea compounds, resulting in the production of bioactive molecules. Consequently, the health benefits associated with tea may stem from both the favorable bacteria it nurtures and the metabolites produced by these microbes. The gut microbiota plays a vital role in mediating the systemic immune homeostasis linked to tea consumption, functioning through complex pathways that involve the gut–lung, gut–brain, and gut–liver axes. Recent studies have sought to establish connections between tea, its bioactive compounds, and immune regulation via the gut microbiota. In this paper, we aim to summarize the latest research findings in this field.
Inflammatory bowel disease (IBD) is a chronic gastrointestinal condition with increasing global prevalence. Current therapies are limited, leading to exploration of novel treatments like Pu-erh tea, a fermented tea recognized for its health benefits. This study shows that long-term consumption of Pu-erh tea significantly reduces IBD symptoms in DSS-induced mice by moderating inflammation and enhancing oxidative responses in the colon. Pu-erh tea notably increases the abundance of specific gut microbiota, particularly enhancing Firmicutes, Bacteroidota, and Proteobacteria phyla, and raising levels of Lactobacillus and Muribaculaceae genera. Key species such as Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus murinus also showed increased abundance. Additionally, Pu-erh tea helps restore the integrity of the intestinal barrier. These findings highlight the potential of Pu-erh tea as a complementary dietary strategy for IBD, potentially improving disease management and patient outcomes through its effects on the intestinal microbiota and mucosal barrier.
Postbiotics are the inactive bacteria and/or metabolites of beneficial microbes which have been recently found to be as effective as their live probiotic. This study aimed to evaluate the benefits of Lactobacillus plantarum (LP)-derived postbiotics on ameliorating Salmonella-induced neurological dysfunctions. Mice were pretreated with LP postbiotics (heat-killed bacteria or the metabolites) or active bacteria, and then challenged with Salmonella enterica Typhimurium (ST). Results showed that LP postbiotics, particularly the metabolites, effectively prevented ST infection in mice, as evidenced by the inhibited weight loss, bacterial translocation, and tissue damages. The LP postbiotics markedly suppressed brain injuries and neuroinflammation (the decreased interleukin (IL)-1β and IL-6, and the increased IL-4 and IL-10). Behavior tests indicated that LP postbiotics, especially the metabolites, protected mice from ST-induced anxiety and depressive-like behaviors and cognitive impairment. A significant modulation of neuroactive molecules (5-hydroxytryptamine, gamma-aminobutyric acid, brain-derived neurotrophic factor, dopamine, acetylcholine, and neuropeptide Y) was also found by LP postbiotic pretreatment. Microbiome analysis revealed that LP postbiotics optimized the cecal microbial composition by increasing Helicobacter, Lactobacillus and Dubosiella, and decreasing Mucispirillum, norank_f_Oscillospiraceae, and Eubacterium_siraeum_group. Moreover, LP postbiotics inhibited the reduction of short-chain fatty acids caused by ST infection. Pearson's correlation assays further confirmed the strong relationship of LP postbiotics-mediated benefits and gut microbiota. This study highlights the effectiveness of postbiotics and provide a promising strategy for preventing infection-induced brain disorders by targeting gut–brain axis.
Chronic visceral pain can occur in many disorders, the most common of which is irritable bowel syndrome (IBS). Moreover, depression is a frequent comorbidity of chronic visceral pain. The P2X7 receptor is crucial in inflammatory processes and is closely connected to developing pain and depression. Gallic acid, a phenolic acid that can be extracted from traditional Chinese medicine, has been demonstrated to be anti-inflammatory and anti-depressive. In this study, we investigated whether gallic acid could alleviate comorbid visceral pain and depression by reducing the expression of the P2X7 receptor. To this end, the pain thresholds of rats with comorbid visceral pain and depression were gauged using the abdominal withdraw reflex score, whereas the depression level of each rat was quantified using the sucrose preference test, the forced swimming test, and the open field test. The expressions of the P2X7 receptor in the hippocampus, spinal cord, and dorsal root ganglion (DRG) were assessed by Western blotting and quantitative real-time PCR. Furthermore, the distributions of the P2X7 receptor and glial fibrillary acidic protein (GFAP) in the hippocampus and DRG were investigated in immunofluorescent experiments. The expressions of p-ERK1/2 and ERK1/2 were determined using Western blotting. The enzyme-linked immunosorbent assay was utilized to measure the concentrations of IL-1β, TNF-α, and IL-10 in the serum. Our results demonstrate that gallic acid was able to alleviate both pain and depression in the rats under study. Gallic acid also reduced the expressions of the P2X7 receptor and p-ERK1/2 in the hippocampi, spinal cords, and DRGs of these rats. Moreover, gallic acid treatment decreased the serum concentrations of IL-1β and TNF-α, while raising IL-10 levels in these rats. Thus, gallic acid may be an effective novel candidate for the treatment of comorbid visceral pain and depression by inhibiting the expressions of the P2X7 receptor in the hippocampus, spinal cord, and DRG.
Evidence from human cohorts indicates that chronic insomnia is associated with higher risk of cardiometabolic diseases (CMD), yet whether gut microbiota plays a role is unclear. Here, in a longitudinal cohort (n = 1809), we find that the gut microbiota-bile acid axis may link the positive association between chronic insomnia and CMD. Ruminococcaceae UCG-002 and Ruminococcaceae UCG-003 are the main genera mediating the positive association between chronic insomnia and CMD. These results are also observed in an independent cross-sectional cohort (n = 6122). The inverse associations between those gut microbial biomarkers and CMD are mediated by certain bile acids (isolithocholic acid, muro cholic acid and nor cholic acid). Habitual tea consumption is prospectively associated with the identified gut microbiota and bile acids in an opposite direction compared with chronic insomnia. Our work suggests that microbiota-bile acid axis may be a potential intervention target for reducing the impact of chronic insomnia on cardiometabolic health. Chronic insomnia is associated with cardiometabolic diseases. Here, in two clinical cohorts (n = 7,931), authors show that gut microbiota-bile acid axis may be an intervention target to attenuate the impact of chronic insomnia on cardiometabolic health.
Several lines of evidence suggest that stress induces the neurovascular dysfunction associated with increased blood–brain barrier (BBB) permeability, which could be an important pathology linking stress and psychiatric disorders, including major depressive disorder (MDD). However, the detailed mechanism resulting in BBB dysfunction associated in the pathophysiology of MDD still remains unclear. Herein, we demonstrate the role of vascular endothelial growth factor (VEGF), a key mediator of vascular angiogenesis and BBB permeability, in stress-induced BBB dysfunction and depressive-like behavior development. We implemented an animal model of depression, chronic restraint stress (RS) in BALB/c mice, and found that the BBB permeability was significantly increased in chronically stressed mice. Immunohistochemical and electron microscopic observations revealed that increased BBB permeability was associated with both paracellular and transcellular barrier alterations in the brain endothelial cells. Pharmacological inhibition of VEGF receptor 2 (VEGFR2) using a specific monoclonal antibody (DC101) prevented chronic RS-induced BBB permeability and anhedonic behavior. Considered together, these results indicate that VEGF/VEGFR2 plays a crucial role in the pathogenesis of depression by increasing the BBB permeability, and suggest that VEGFR2 inhibition could be a potential therapeutic strategy for the MDD subtype associated with BBB dysfunction.
Sleep disorders have received widespread attention nowadays, which have been promoted by the accelerated pace of life, unhealthy diets and lack of exercise in modern society. The chemical medications to improve sleep has shown serious side effects and risks with high costs. Therefore, it is urgent to develop efficient nutraceuticals from natural sources to ensure sleep quality as a sustainable strategy. As the second most consumed beverage worldwide, the health-promoting effects of tea have long been widely recognized. However, the modulatory effect of teas on sleep disorders has received much less attention. Tea contains various natural sleep-modulating active ingredients such as L-theanine (LTA), caffeine, tea polyphenols (TPP), tea pigments, tea polysaccharides (TPS) and γ-aminobutyric acid (GABA). This review focuses on the potential influence and main regulating mechanisms of different tea active ingredients on sleep, including being absorbed by the small intestine and then cross the blood-brain barrier to act on neurons in the brain as neurotransmitters, manipulating the immune system and further affect sleep-wake cycle by regulating the levels of cytokines, and controlling the gut microbes to maintain the homeostasis of circadian rhythm. Current research progress and limitations are summarized and several future development directions are also proposed. This review hopes to provide new insights into the future elucidation of the sleep-regulating mechanisms of different teas and their natural active ingredients and the development of tea-based functional foods for alleviating sleep disorders.
• Highlights
• • Natural sleep-modulating active ingredients in tea have been summarized.
• • Influences of drinking tea or tea active ingredients on sleep are reviewed.
• • Three main regulating mechanisms of tea active ingredients on sleep are explained.
• • The associations among nervous system, immune system and intestinal microbiota are investigated.
• • The potential of developing delivery carriers for tea active ingredients is proposed.
Growing evidence supports the concept that bidirectional brain–gut microbiome interactions play an important mechanistic role in aging, as well as in various neuropsychiatric conditions including depression. Gray matter volume (GMV) deficits in limbic regions are widely observed in geriatric depression (GD). We therefore aimed to explore correlations between gut microbial measures and GMV within these regions in GD. Sixteen older adults (>60 years) with GD (37.5% female; mean age, 70.6 (SD = 5.7) years) were included in the study and underwent high-resolution T1-weighted structural MRI scanning and stool sample collection. GMV was extracted from bilateral regions of interest (ROI: hippocampus, amygdala, nucleus accumbens) and a control region (pericalcarine). Fecal microbiota composition and diversity were assessed by 16S ribosomal RNA gene sequencing. There were significant positive associations between alpha diversity measures and GMV in both hippocampus and nucleus accumbens. Additionally, significant positive associations were present between hippocampal GMV and the abundance of genera Family_XIII_AD3011_group, unclassified Ruminococcaceae, and Oscillibacter, as well as between amygdala GMV and the genera Lachnospiraceae_NK4A136_group and Oscillibacter. Gut microbiome may reflect brain health in geriatric depression. Future studies with larger samples and the experimental manipulation of gut microbiome may clarify the relationship between microbiome measures and neuroplasticity.
Keywords: gray matter volume (GMV); gut–brain axis; geriatric depression (GD)
Objective
This study examined problematic mobile phone use (PMPU) and its relationship with life satisfaction in Chinese university students during the pandemic.
Methods
An anonymous online survey was conducted in a university in China. The Mobile Phone Addiction Index (MPAI) and the Satisfaction with Life Scale (SWLS) were used to assess the severity of problematic mobile phone use and life satisfaction, respectively. Data on demographic and health-related factors were also collected.
Results
A total of 1,491 undergraduate students (73.3% were male) completed the survey. On average, students in the survey reported spending 7.4 ± 4.3 h/day on phone use. Their MPAI score was 38.1 ± 13.3 and SWLS score was 24.9 ± 6.8, respectively. After controlling for confounding factors, the MPAI score was significantly associated with lower life satisfaction. Multiple linear regression revealed that higher monthly allowances, frequent insomnia, longer phone use duration were significantly associated with PMPU.
Conclusion
University students in China spend nearly half of their waking hours on mobile phone use, significantly longer than before the COVID-19 pandemic. PMPU is associated with insomnia, lower life satisfaction and higher allowances. If the trend continues after the pandemic, interventions may be needed. Increase in-person interactions, limiting online social and gaming time, awareness campaign may be effective in reducing the impact of PMPU and improve life satisfaction.
Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.
Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.
The gut microbiome is known to be involved in depression development. Thus, phytochemicals changing gut microbiota may alleviate depression-like behaviors. Coniferyl ferulate (CF) is a long studied natural product and known to alleviate psychiatric disorders. However, its mechanism of action remains unclear. In this experimental study, oral administration of 50 mg kg-1 CF once daily attenuated weight loss and depression-like and anxiety-like behaviors induced by chronic unpredicted mild stress (CUMS) in mice. Four weeks of CF administration significantly ameliorated colonic inflammation, lowered the levels of IL-6, IL-1β, and TNF-α, and restructured the gut microbiome, and microbial metabolism. Intestinal microbiota can impact the development and function of the brain via the microbiota-gut-brain axis. Therefore, oral administration of CF is a promising nutritional strategy to treat CUMS-induced depression via the regulation of microbiota and microbial metabolism.
Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.
Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs resilience and emotion‐related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder and posttraumatic stress disorder is increasing in our modern societies. Unfortunately, 30‐50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion‐related biology to gain mechanistic insights that could lead to innovative therapies. Here we provide an overview of inflammation‐related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention and thus the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation‐driven leakiness of the blood‐brain and gut barriers in emotion regulation and mood are highlighted. Stress‐induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut‐brain axis which is central to production of mood‐related neurotransmitter serotonin. Novel therapeutic approaches such as anti‐inflammatory drugs, the fast‐acting antidepressant ketamine and probiotics could directly act on the mechanisms described here improving mood disorder‐associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation.
The intestinal microbiota plays an important role in the pathophysiology of depression. As determined, the microbiota influences the shaping and modulation of the functioning of the gut–brain axis. The intestinal microbiota has a significant impact on processes related to neurotransmitter synthesis, the myelination of neurons in the prefrontal cortex, and is also involved in the development of the amygdala and hippocampus. Intestinal bacteria are also a source of vitamins, the deficiency of which is believed to be related to the response to antidepressant therapy and may lead to exacerbation of depressive symptoms. Additionally, it is known that, in periods of excessive activation of stress reactions, the immune system also plays an important role, negatively affecting the tightness of the intestinal barrier and intestinal microflora. In this review, we have summarized the role of the gut microbiota, its metabolites, and diet in susceptibility to depression. We also describe abnormalities in the functioning of the intestinal barrier caused by increased activity of the immune system in response to stressors. Moreover, the presented study discusses the role of psychobiotics in the prevention and treatment of depression through their influence on the intestinal barrier, immune processes, and functioning of the nervous system.
The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.
Propionate has been reported to exert antidepressant effects, but high-dose propionate may induce autism-like symptoms in experimental animals through induction of dysbiosis of neurotransmitters. The bi-directional effects of propionate seem to be dose-dependent. However, due to the pathological discrepancies between depression and autism, conclusions drawn from autism may not be simply transferable to depression. The effect and underlying action mechanisms of high-dose propionate on depression remains undetermined. To investigate the effects of propionate on depression, propionate dose gradients were intravenously administrated to rats exposed to chronic unpredictable mild stress (CUMS) for 1 week. Results of these behavioral tests demonstrate that low-dose propionate (2 mg/kg body weight/day) induces antidepressant effect through bodyweight recovery, elevated reward-seeking behaviors, and reduced depression-like behaviors, while high-dose propionate (200 mg/kg body weight/day) induces prodepressant effects opposite of those of low-dose propionate. A comprehensive profiling of neurotransmitters in the hippocampus demonstrated that CUMS induces reduction of NE (Norepinephrine), DA (Dopamine). GABA (γ-aminobutyric acid) was recovered by low-dose propionate, while high-dose propionate exerted more complicated effects on neurotransmitters, including reduction of NE, DA, 5-Hydroxytryptamine and Tryptophan, and increase of GABA, Kynurenine, Homovanillic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine. The neurotransmitters disturbed by high-dose propionate suggest metabolic disorders in the hippocampus, which were confirmed by the clear group separation in PCA of metabolomic profiling. The results of this study demonstrate the double-edged dose-dependent effects of propionate on depression and suggest potential cumulative toxicity of propionate as a food additive to mood disorders.
Besides generating vision, light modulates various physiological functions, including mood. While light therapy applied in the daytime is known to have anti-depressive properties, excessive light exposure at night has been reportedly associated with depressive symptoms. The neural mechanisms underlying this day–night difference in the effects of light are unknown. Using a light-at-night (LAN) paradigm in mice, we showed that LAN induced depressive-like behaviors without disturbing the circadian rhythm. This effect was mediated by a neural pathway from retinal melanopsin-expressing ganglion cells to the dorsal perihabenular nucleus (dpHb) to the nucleus accumbens (NAc). Importantly, the dpHb was gated by the circadian rhythm, being more excitable at night than during the day. This indicates that the ipRGC→dpHb→NAc pathway preferentially conducts light signals at night, thereby mediating LAN-induced depressive-like behaviors. These findings may be relevant when considering the mental health effects of the prevalent nighttime illumination in the industrial world.
Some recent clinical and preclinical evidence suggests that neuroinflammation is a key factor that interacts with the three neurobiological correlates of major depressive disorder: depletion of brain serotonin, dysregulation of the hypothalamus‐pituitary‐adrenal (HPA) axis and alteration of the continuous production of adult‐generated neurons in the dentate gyrus of the hippocampus. This review discusses the main players in brain immunity as well as how inflammation interacts with the above three mechanisms. It is reported that kynurenine (KYN) pathway alteration in favour of its excitotoxic component and HPA axis dysregulation have the common effect of increasing extracellular glutamate levels and glutamate neurotransmission, which can impact hippocampal neurogenesis. This pathophysiological cascade appears to be triggered or sustained and reinforced by any chronic inflammatory condition involving increased circulating markers of inflammation that are able to cross the blood‐brain barrier and activate microglia; it can also be the consequence of primary brain neuroinflammation, such as in neurodegenerative disorders with early manifestations that are frequently depressive symptoms. Further recent data indicate that primary microglial activation may also result from a direct impact of chronic stress on vascular function. The intricated dynamic crosstalk between neuroinflammation and other relevant neurobiological correlates of depression add to evidence that neuroinflammation may be a key therapeutic target for future therapeutic strategies in major depressive disorder.
Significance
Thirty to fifty percent of depressed individuals are unresponsive to commonly prescribed antidepressant treatments, suggesting that biological mechanisms, such as stress-induced inflammation and blood vessel dysfunction, remain untreated. The blood–brain barrier is the ultimate frontier between the brain and harmful toxins or inflammatory signals circulating in the blood. Depression and vulnerability to chronic social stress are associated with loss of this barrier integrity; however, the mechanisms involved remain poorly understood. Identification of adaptations leading to resilience under stressful conditions could help develop novel treatments. Here we combined behavioral, pharmacological, and cell-specific gene profiling experiments in mice with epigenetic, molecular, and anatomical analysis of human samples to unravel mechanisms with therapeutic potential to protect the brain and promote resilience.
The azoxymethane (AOM)/dextran sulfate sodium (DSS) murine model is commonly used to study colitis-associated cancer. The human commensal bacterium, enterotoxigenic Bacteroides fragilis (ETBF) secretes the Bacteroides fragilis toxin (BFT) which is necessary and sufficient to cause colitis. We report that BALB/c mice infected with WT-ETBF and administered three cycles of AOM/DSS developed numerous, large-sized polyps predominantly in the colorectal region. In addition, AOM/DSS-treated BALB/c mice orally inoculated with wild-type nontoxigenic Bacteroides fragilis (WT-NTBF) overexpressing bft (rETBF) developed numerous polyps whereas mice infected with WT-NTBF overexpressing a biologically inactive bft (rNTBF) did not promote polyp formation. Unexpectedly, the combination of AOM+ETBF did not induce polyp formation whereas ETBF+DSS did induce polyp development in a subset of BALB/c mice. In conclusion, WT-ETBF promoted polyp development in AOM/DSS murine model with increased colitis in BALB/c mice. The model described herein provides an experimental platform for understanding ETBF-induced colonic tumorigenesis and studying colorectal cancer in wild-type mice.
Dust storms are environmental natural events that transport high concentrations of particulate matter (PM) in living spaces. Recent epidemiological studies have shown that air pollution is associated with stroke. In the present study we aimed to investigate the probable protective effects of gallic acid (GA) on blood-brain barrier (BBB) disruption, brain oxidative stress, anxiety, depression, locomotion behaviors, and changes of hippocampal local electroencephalogram (local EEG) power induced by 4-vessel transient occlusion (4VO I/R) following exposure to dusty PM in rats. Male Wistar rats were divided randomly into eight groups: (1) vehicle+Sham (Veh + Sh), (2) vehicle+4VO I/R (Veh + I/R), (3) gallic acid+sham (GA + Sh), (4) gallic acid+4VO I/R (GA + I/R), (5) vehicle+PM (Veh + PM), (6) PM + 4VO I/R (PM + I/R), (7) gallic acid+PM + Sham (GA + PM + Sh), and (8) gallic acid+PM + 4Vo I/R (GA + PM + I/R). 4VO type of I/R was induced after 10 days of pretreatment by GA 100 mg/kg/2 ml/ip, or 2 ml/kg/ip, normal saline as vehicle (Veh) and exposure to dust storm composed of dusty PM (DPM, 2000–8000 μg/m3), 60 min daily for consecutive 10 days) simultaneously. Seventy-two hours after I/R induction, all behavioral tests and BBB permeability evaluation were done. Hippocampus local EEG was recorded just before and 72 h after I/R induction, and finally brain tissue oxidative stress was assayed. Data showed that 4VO I/R following exposure to DPM increased BBB permeability (p < 0.001), brain oxidative stress (p < 0.001), induced anxiety (p < 0.001), depression (p < 0.01), locomotion impairment (p < 0.001), superoxide dismutase (SOD) activity, and local EEG power also were decreased in PM + Sh (p < 0.001). Pretreatment with GA reversed BBB permeability and MDA. Our findings suggest that GA is a probable protective agent against adverse effects of both I/R and exposure to DPM and also in I/R subjects exposed to DPM. The beneficial effects of GA may induce by its antioxidative and anti-inflammatory properties.
Major depression is one of the leading causes of disability, morbidity, and mortality worldwide. The brain–gut axis functions are disturbed, revealed by a dysfunction of the brain, immune system, endocrine system, and gut. Traditional depression treatments all target the brain, with different drugs and/or psychotherapy. Unfortunately, most of the patients have never received any treatment. Studies indicate that gut microbiota could be a direct cause for the disorder. Abnormal microbiota and the microbiota–gut–brain dysfunction may cause mental disorders, while correcting these disturbance could alleviate depression. Nowadays, the gut microbiota modulation has become a hot topic in treatment research of mental disorders. Depression is closely related with the health condition of the brain–gut axis, and maintaining/restoring the normal condition of gut microbiota helps in the prevention/therapy of mental disorders.
Background/objectives:
Recent epidemiological studies have examined associations between various types of non-alcoholic beverage consumption and risk of depression, but the associations were inconsistent. To provide a quantitative assessment of this association, we performed a systematic review and meta-analysis of observational studies.
Subjects/methods:
We searched PubMed and Web of Science databases through February 2017 for eligible studies and examined the reference lists of the retrieved articles. A random-effects model was used to calculate pooled relative risks (RR) with 95% CIs after adjusting for important confounders.
Results:
We identified fifteen observational studies (9 cross-sectional studies; 6 prospective studies) of beverage consumption and depression, including 20,572 cases of depression among 347,691 participants. For coffee and tea consumption, the pooled RRs of depression for the high vs. low categories of consumption were 0.73 (95% CI 0.59-0.90) and 0.71 (95% CI 0.55-0.91), respectively. For soft drinks, however, the pooled RR for the high vs. low category of consumption was 1.36 (95% CI 1.24-1.50). The inverse association with coffee or tea consumption and the positive association with soft drink consumption for risk of depression did not vary by gender, country, high consumption category, and adjustment factors such as alcohol, smoking and physical activity.
Conclusions:
Our findings suggest that high consumption of coffee and tea may reduce the risk of depression, while high consumption of soft drinks may increase the risk of depression. Further well-designed large prospective studies are needed to provide definitive evidence to address the effects of various types of beverages on risk of depression.
Depression is a polygenic and highly complex psychiatric disorder that remains a major burden on society. Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are some of the most commonly prescribed drugs worldwide. In this review, we will discuss the evidence that links serotonin and serotonin receptors to the etiology of depression and the mechanisms underlying response to antidepressant treatment. We will then revisit the role of serotonin in three distinct hypotheses that have been proposed over the last several decades to explain the pathophysiology of depression: the monoamine, neurotrophic, and neurogenic hypotheses. Finally, we will discuss how recent studies into serotonin receptors have implicated specific neural circuitry in mediating the antidepressant response, with a focus being placed on the hippocampus.
Caffeine is the most widely consumed psychoactive drug in the world. Natural sources of caffeine include coffee, tea, and chocolate. Synthetic caffeine is also added to products to promote arousal, alertness, energy, and elevated mood. Over the past decade, the introduction of new caffeine-containing food products, as well as changes in consumption patterns of the more traditional sources of caffeine, has increased scrutiny by health authorities and regulatory bodies about the overall consumption of caffeine and its potential cumulative effects on behavior and physiology. Of particular concern is the rate of caffeine intake among populations potentially vulnerable to the negative effects of caffeine consumption: pregnant and lactating women, children and adolescents, young adults, and people with underlying heart or other health conditions, such as mental illness. Here, we review the research into the safety and safe doses of ingested caffeine in healthy and in vulnerable populations. We report that, for healthy adults, caffeine consumption is relatively safe, but that for some vulnerable populations, caffeine consumption could be harmful, including impairments in cardiovascular function, sleep, and substance use. We also identified several gaps in the literature on which we based recommendations for the future of caffeine research.
Tea (Camellia sinensis) is a beverage beneficial to health and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of heteropolysaccharides bound with proteins. There is evidence showing that TPS not only improves immunity but also has various bioactivities, such as antioxidant, antitumor, antihyperglycemia, and anti-inflammation. However, inconsistent results concerning chemical composition and bioactivity of TPS have been published in recent years. The advances in chemical composition and bioactivities of TPS are reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS are also discussed.
Research on the neurobiology of the kynurenine pathway has suffered years of relative obscurity because tryptophan degradation, and its involvement in both physiology and major brain diseases, was viewed almost exclusively through the lens of the well-established metabolite serotonin. With increasing recognition that kynurenine and its metabolites can affect and even control a variety of classic neurotransmitter systems directly and indirectly, interest is expanding rapidly. Moreover, kynurenine pathway metabolism itself is modulated in conditions such as infection and stress, which are known to induce major changes in well-being and behaviour, so that kynurenines may be instrumental in the etiology of psychiatric and neurological disorders. It is therefore likely that the near future will not only witness the discovery of additional physiological and pathological roles for brain kynurenines, but also ever-increasing interest in drug development based on these roles. In particular, targeting the kynurenine pathway with new specific agents may make it possible to prevent disease by appropriate pharmacological or genetic manipulations.
Depression is a global public health issue with high morbidity and mortality, which tends to cause fatigue, inability to concentrate, insomnia, and loss of appetite, especially represented by major depressive disorder (MDD). Pathologically, depression is associated with hyperactivity of hypothalamic–pituitaryadrenal (HPA) axis, inflammation, loss of monoaminergic system, and disturbance of gut microbiota. Epidemiological studies have
shown that regular tea drinking can reduce the risk of depression. Tea bioactive compounds (L-theanine, catechin, tea pigment and GABA) can regulate depression by inhibiting hyperactive HPA axis, reducing the inflammatory response, restoring the monoaminergic system, inhibiting monoamine oxidase levels, increasing the enrichment of intestinal flora and promoting microbial-gut-brain axis activity. This review discusses the composition, structure, bioavailability and safety of bioactive components from tea, and focuses on exploring the possible pathways of tea bioactive compounds in the regulation of depression. In addition, the low bioavailability of natural bioactive compounds from tea limits the efficacy on depression. Emerging technologies (such as
metabolomics, proteomics, and genomics) and nano-encapsulation can be utilized to improve the stability and bioavailability of tea active ingredients, and reduce the potential biotoxicity. The review provides a theoretical basis of utilization of tea active compounds for formulating the prevention and treatment of depression.
Depression is a risk factor for Alzheimer’s (AD) and cardiovascular diseases (CVD). Therefore, depression treatment restricts its deteriorating effects on mood, memory and CV system. Fluoxetine is the most widely used antidepressant drug, it has neuroprotective effect through its antioxidant/anti-inflammatory properties. The current study investigated for the first-time the cross link between depression, AD and CVD besides, role of fluoxetine in mitigating such disorders. Depression was induced in rats by social isolation (SI) for 12 weeks, AlCL3 (70 mg/kg/day, i.p.) was used to induce AD which was administered either in SI or normal control (NC) grouped rats starting at 8th week till the end of the experiment, fluoxetine (10 mg/kg/day, p.o) treatment also was started at 8th week. SI and AD showed a statistically significant deteriorated effect on behavioral, neurochemical and histopathological analysis which was exaggerated when two disorder combined than each alone. Fluoxetine treatment showed protective effect against SI, AD and prevents exacerbation of CVD. Fluoxetine improved animals’ behavior, increased brain monoamines, BDNF besides increased antioxidant defense mechanism of SOD, TAC contents and increased protein expression of Nrf2/HO-1 with significant decrease of AChE activity, β-amyloid, Tau protein, MDA, TNF-α, IL1β contents as well as decreased protein expression of NF-kB, TLR4, NLRP3 and caspase1. It also showed cardioprotective effects as it improved lipid profile with pronounced decrease of cardiac enzymes of CK-MB, troponin and MEF2. In conclusion, fluoxetine represents as a promising drug against central and peripheral disorders through its anti-inflammatory/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.
Pu-erh tea is post-fermented sun-dried tea leaves of Camellia sinensis (Linn.) var. assamica (Masters) Kitamura plant, native to Yunnan, China. Pu-erh tea is a highly prized commodity with unique aroma and taste and multiple health effects. This review overviews the chemical constituents, tentative bioactive compounds and their mechanisms responsible for bioactivities of Pu-erh tea. The bioactivities include antioxidative, antimutagenic, antimicrobial, laxative and neuroprotective activities, and controlling or preventing hypercholesterolemia, hyperglycemia, obesity, diabetes, osteoporosis and Alzheimer’s disease. Limited human trials hardly convince therapeutic efficiency of Pu-erh tea. Raw and ripened Pu-erh tea possess their respective sensory characteristics, chemical and microbial diversities. Chemical and biological differences between Pu-erh and other tea types could be explained by different extents of their respective processing-induced compound transformations. Undesirable heavy metals, mycotoxins and other biocontaminants detected in Pu-erh tea relate to growing conditions of tea plants, processing and storage conditions. Chemistry- and nutrition-derived mechanisms for tea pricing are lacking. Decontamination strategies and future studies for quality improvement are recommended.
Angiotensin II, the effector peptide of the renin-angiotensin system, is not only a pivotal peptide implicated in the regulation of blood pressure but also a key mediator of the inflammatory processes that play an important role in the pathology of hypertension-related cSVD. Harpagide is the major bioactive constituent of Scrophulariae Radix widely used in traditional Chinese medicine for numerous diseases including hypertension. The present study aimed to investigate the effect of harpagide on Ang II-induced neuroinflammation and the potential mechanism. Pretreated with harpagide or resatorvid (the TLR4 pathway inhibitor), BV2 cells were treated with Ang II or LPS (the TLR4 activator). NO, pro-inflammatory cytokines, the proteins on TLR4/MyD88/NF-κB signaling pathway and the expression of CD86, CD206, TREM2 in BV2 cells were detected respectively. Subsequently, the effects of harpagide on neurotoxicity and BBB destruction triggered by Ang II-induced neuroinflammation were investigated in the co-cultures of BV2 microglia/HT22 hippocampal neurons, BV2 microglia/bEnd.3 endotheliocyte and BV2 microglia/BBB monolayer model. We found that Ang II converted microglia into M1 state and resulted in neuroinflammation through activating TLR4/MyD88/NF-κB signaling pathway. It also triggered the imbalance of TLR4/TREM2 in microglia. Ang II-mediated inflammation microglia further led to neuronal apoptosis and BBB damage. Harpagide showed the effect of alleviating Ang II-mediated neuroinflammation as well as the resulting neurotoxicity and BBB destruction through inhibiting the TLR4/MyD88/NF-κB pathway. The anti-inflammatory and neuroprotective effect of harpagide suggested that it might be a potential therapeutic strategy in hypertensive cSVD.
Background
Dark tea is a post-fermented tea with unique organoleptic characteristics. A unique microbial fermentation procedure is involved in dark tea processing that is considered a major factor to manage the quality of dark tea. Dark tea is gaining increasing attention recently because it contains various bioactive compounds with diverse biological functions.
Scope and approach
This review summarizes the microbial fermentation process, main bioactive compounds, and important biological functions or health benefits of dark tea, emphasizing its protective effects against different diseases and relevant molecular mechanisms, and proposes the perspectives in research and application of dark tea.
Key findings and conclusions
Functional core microorganism-mediated bioconversion is crucial for the formation of dark tea's main quality components during the fermentation period. Dark tea contains a variety of bioactive compounds, including alkaloids, free amino acids, peptides, polyphenols, pigments, polysaccharides, and volatile compounds. Consumption of dark teas has been linked to multiple health benefits, such as antioxidant, anti-obesity, anti-diabetic, anti-cancer, cardiovascular protective, gastrointestinal protective, hepatoprotective, neuroprotective, and photoprotective activities. Future studies focusing on the health mechanisms of dark teas and the potential applications of dark tea in the food, pharmaceutical, and medical industries are guaranteed.
Background: Abnormal energy metabolism is often documented in the brain of patients and rodents with depression. In metabolic stress, acetate serves as an important source of acetyl coenzyme A (Ac-CoA). However, its exact role and underlying mechanism remain to be investigated.
Method: We used chronic social failure stress (CSDS) to induce depression-like phenotype of C57BL/6J mice. The drugs were administered by gavage. We evaluated the depressive symptoms by sucrose preference test, social interaction, tail suspension test and forced swimming test. The dendritic branches and spine density were detected by Golgi staining, mRNA level was analyzed by real-time quantitative RT-PCR, protein expression level was detected by western blot, and the content of Ac-CoA was detected by ELISA kit.
Result: The present study found that acetate supplementation significantly improved the depression-like behaviors of mice either in acute forced swimming test (FST) or in CSDS model and that acetate administration enhanced the dendritic branches and spine density of the CA1 pyramidal neurons. Moreover, the down-regulated levels of BDNF and TrkB were rescued in the acetate-treated mice. Of note, chronic acetate treatment obviously lowered the transcription level of HDAC2, HDAC5, HDAC7, HDAC8, increased the transcription level of HAT and P300, and boosted the content of Ac-CoA in the nucleus, which facilitated the acetylation levels of histone H3 and H4.
Limitations: The effect of acetate supplementation on other brain regions is not further elucidated.
Conclusion: These findings indicate that acetate supplementation can produce antidepressant-like effects by increasing histone acetylation and improving synaptic plasticity in hippocampus.
Antenatal obesity increases the risk of postpartum depression. Previous research found that dietary fiber supplementation could alleviate mental behavioral disorders. The present study aims to uncover the effects of high-dietary fiber intake on high-fat diet (HFD)-induced depressive-like behaviors and its underlying mechanism. Female C57BL6/J mice were fed with HFD to establish an antenatal obese model. A high-dietary fiber intake (inulin, 0.037 g/kcal) significantly attenuated cognitive deficits and depressive-like behaviors in the maternal mice after the offspring weaning. High-dietary fiber intake upregulated the expression of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) and suppressed neuroinflammation. Furthermore, high-dietary fiber intake restructured the gut microbiome and elevated the formation of short-chain fatty acids (SCFAs). Correlation analysis indicated that the increase in microbes such as Lactobacillus and S24-7, and SCFAs' levels were positively correlated with behavioral improvements. In conclusion, high-dietary fiber intake is a promising nutritional intervention strategy to prevent antenatal obesity-induced behavioral disorders via a microbiota-gut-brain axis.
The gut microbiota is a complex ecosystem that comprises of more than 100 trillion symbiotic microbial cells. The microbiota, the gut, and the brain form an association, ‘the microbiota-gut-brain axis,’ and synchronize the gut with the central nervous system and modify the behavior and brain immune homeostasis. The bidirectional communication between gut and brain occurs via the immune system, the vagus nerve, the enteric nervous system, and microbial metabolites, including short-chain fatty acids (SCFAs), proteins, and tryptophan metabolites. Recent studies have implicated the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we present an overview of gut microbiota, including Firmicutes, Bacteroidetes, SCFA, tryptophan, bacterial composition, besides age-related changes in gut microbiota composition, the microbiota-gut-brain axis pathways, the role of gut metabolites in amyloid-beta clearance, and gut microbiota modulation from experimental and clinical AD models. Understanding the role of the microbiota may provide new targets for treatment to delay the onset, progression, or reverse AD, and may help in reducing the prevalence of AD.
Background
Pu'er tea, a type of post-fermented tea made from Camellia sinensis leaves, has long been widely used in East Asian countries. It is mainly produced in southern China and is effective in preventing obesity due to its ability to break down fat. However, the effects of Pu'er tea on cognitive impairment or neuroinflammation by endotoxin have not yet been studied.
Purpose
Here, we assessed the inhibitory activity of Pu'er tea hot water extract (PTW) on neuroinflammation and cognitive impairment and explored its mechanism.
Study design
The ability of PTW to inhibit cognitive impairment was investigated in a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation and murine microglia BV2 cells.
Methods
We examined whether oral administration of PTW prevented cognitive impairment and LPS-induced neuroinflammation using behavioral tests, Nissl staining, immunohistochemistry, western blotting, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), Griess assay, and enzyme-linked immunosorbent assay (ELISA).
Results
First, Morris water maze (MWM) and passive avoidance (PA) tests demonstrated that oral administration of PTW effectively attenuated LPS-induced spatial memory loss and inhibited neuronal damage of mouse brains. Histopathological analysis showed that PTW repressed LPS-induced expression of the activation markers ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Furthermore, PTW inhibited the expression of amyloidogenesis proteins such as amyloid-β precursor protein (APP), C99, and β-secretase-1 (BACE-1); production of inflammatory proteins such as Iba-1, GFAP, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2; activation of inflammatory pathways; and expression of inflammatory mediator mRNAs in hippocampal tissue. In cultured microglia, PTW treatment inhibited the generation of various inflammatory factors activated by LPS.
Conclusion
Our results in vivo and in vitro demonstrate that PTW effectively prevents cognitive impairment caused by neuroinflammation and is, therefore, a potential candidate for the development of a therapeutic agent for neurodegenerative diseases.
Growing evidence shows that gut microbiota and neuroinflammatory responses play a critical role in the pathogenesis of depression. Our previous study demonstrated that schisandrin (SCH) could reduce proinflammatory factors of depressive mice. Therefore, our present study is to research the potential connection between gut microbial and anti-inflammatory effects of SCH on a depressive mouse model induced by lipopolysaccharide (LPS). We found that SCH pre-treatment could decrease the immobility time of forced swimming test (FST) and tail suspension test (TST). And the results of 16S rRNA demonstrated that SCH pre-administration attenuated the dysbiosis of gut microbiota of depressive mice, along with altered fecal short-chain fatty acids (SCFAs). Furthermore, SCH reduced the levels of proinflammatory factors of depressive mice and the expression of TLR4/NF-κB signaling pathway in the hippocampus. Overall, our study indicated that SCH might recover the gut microbial disorder of depressive mice through suppressing the expression of TLR4/NF-κB signaling pathway.
Mounting evidence suggests that the gut microbiome impacts brain development and function. Gut–brain connections may be mediated by an assortment of microbial molecules that are produced in the gastrointestinal tract, which can subsequently permeate many organs, including sometimes the brain. Studies in animal models have identified molecular cues propagated from intestinal bacteria to the brain that can affect neurological function and/or neurodevelopmental and neurodegenerative conditions. Herein, we describe bacterial metabolites with known or suspected neuromodulatory activity, define mechanisms of signalling pathways from the gut microbiota to the brain and discuss direct effects that gut bacterial molecules are likely exerting on specific brain cells. Many discoveries are recent, and the findings described in this Perspective are largely novel and yet to be extensively validated. However, expanding research into the dynamic molecular communications between gut microorganisms and the CNS continues to uncover critical and previously unappreciated clues in understanding the pathophysiology of behavioural, psychiatric and neurodegenerative diseases.
Green and dark tea extract (GTE/DTE) ameliorate chemical induced-colitis in mice; however, the role of gut microbiota on the anti-colitis effects of green and dark tea in mice remains unclear. This study aims to explore the role of modulations in gut microbes mediated by green and dark tea in colitis mice by a fecal microbiota transplantation (FMT). Our results indicated that GTE and DTE (5 mg/kg bodyweight/day for 4 weeks) exhibited prebiotic effects on the donor mice. Moreover, the FMT treatments (transferring the microbiota daily from the 1g/kg bodyweight fecal sample to each recipient) indicated that, compared with the fecal microbiota from the normal diet treated donor mice, the fecal microbiota from the GTE and DTE treated donor mice significantly ameliorate colitis-related symptoms (e.g., loss of bodyweight, colonic inflammation, loss of barrier integrity, and gut microbiota dysbiosis) and downregulated TLR4/MyD88/NF-κB pathway. Collectively, GTE and DTE ameliorate chemical induced-colitis by modulating gut microbiota.
Background
Short-chain fatty acids (SCFAs) play important physiological roles in human health. Adverse effects on health are known with a low or excessive concentration of SCFAs although the optimal level of SCFAs in the body is unknown yet. The level of endogenous SCFAs is affected by many factors of which gut bacteria are the most important one. However, how gut bacteria and a dietary intervention affect SCFA balance in the gut still needs to be clarified.
Scope and approach
In addition to addressing the importance of a dynamic balance of SCFAs for health, we discuss the factors affecting the dynamic balance of SCFAs, especially the gut SCFA-producing bacteria, including the classification of the bacteria, their response to diet, the SCFAs metabolic pathways and the catalytic mechanisms of the main rate-limiting enzymes.
Key findings and conclusions
SCFAs levels can be regulated endogenously and exogenously. Exogenous regulation delivers SCFAs to gut by esterification with dietary fibres. Endogenous regulation like diet, directly or indirectly affect gut microbiota, including their abundance, fitness and SCFAs production. Until now, 74 bacterial species are reported to produce SCFAs, the metabolic pathways are classified into 4 categories, and the 4 rate-limiting enzymes in the metabolic pathways are summarized. We also propose methods for long-lasting endogenous SCFAs balancing, including identifying the minimum sets of SCFA-producing bacterial group, and possible dietary intervention to form a minimum group of gut microbiota for SCFAs synthesis. An integrated approach will help realize the rational regulation of balanced SCFAs levels to benefit human health.
Increasing evidences point to the effect of gut microbiota on central nervous functions. Supplementation of certain microbial strains have been demonstrated to alleviate the depressive behaviors and neurological abnormality. This study took the approach to screen for an anti-depressive Bifidobacterium longum strain from fourteen candidates, and systematically verified its effect in a chronic stress induced depression mice model. B. longum subsp. infantis CCFM687 could significantly enhance the biosynthesis of 5-hydroxytryptamine (5-HTP) in vitro in RIN14B cells through up-regulation of the Tph1 gene expression. Administration of CCFM687 in mice significantly improved the scores in behavioral tests, and increased the level of 5-HTP and serotonin (5-HT) in prefrontal cortex (PFC) of brain. The brain-derived neurotrophic factor (BDNF) in PFC was also increased, possibly through the 5-HT1A-CREB-BDNF pathway. In addition, CCFM687 alleviated the hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis response, and accordingly reversed the peripheral inflammation status. Moreover, the stress-induced structural and functional dysbiosis of gut microbiome was improved by CCFM687, through increased alpha diversity and abundance of butyrate producing bacteria, in conjunction with inhalation of pathogenic gene expression. In summary, these results indicate that supplementation of B. longum subsp. infantis CCFM687 may prevent the onset of depression from chronic stress, and RIN14B could serve as an efficient cell model for rapid screening the anti-depressive probiotics.
Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.
Background:
Outdoor light at night (LAN) is an increasingly prevalent type of environmental pollution. Studies have demonstrated that outdoor LAN can disrupt circadian rhythms, potentially contributing to insomnia, cancer, cardiovascular disease, and metabolic changes in humans. We investigated the association of outdoor LAN with depressive symptoms and suicidal behaviors in South Korean adults.
Methods:
This study used data from the 2009 Korean Community Health Survey, a representative sample dataset. Study population consisted of 113,119 participants for the assessment of depressive symptoms and 152,159 participants for the assessment of suicidal behavior. Depressive symptoms were measured using the Korean version of the Center for Epidemiologic Studies Depression Scale (depressive symptoms, score of > 16). Suicidal behaviors were defined as the experience of suicidal ideation or attempt. Outdoor LAN was estimated by satellite data from the National Centers for Environmental Information.
Results:
Participants with depressive symptoms or history of suicidal behaviors were more likely to have exposure to outdoor LAN than those without depressive symptoms or suicidal behaviors. Compared with adults living in areas exposed to the lowest outdoor LAN, those living in areas exposed to the highest levels had higher likelihood depressive symptoms (OR = 1.29; 95% CI: 1.15-1.46) or suicidal behaviors (OR = 1.27; 95% CI: 1.16-1.39). Significant dose-response relationships were observed between outdoor LAN and the odds of depressive symptoms and suicidal behaviors.
Conclusion:
Outdoor LAN was found to be significantly associated with depressive symptoms and suicidal behaviors, suggesting that it may be an environmental contributor to mental health problems.
Background:
Alexithymia is an important predictor of mobile phone addiction. Enhancing and improving college students' mental health can reduce the rate of mobile phone addiction. However, it is not clear about the role of depression, anxiety and stress in the relationship between college students' alexithymia and mobile phone addiction.
Methods:
A total of 1105 college students were tested with the Toronto Alexithymia Scale, the Depression Anxiety Stress Scale and the Mobile Phone Addiction Index.
Results:
An individual's level of alexithymia was significantly correlated with depression, anxiety, stress and mobile phone addiction. Alexithymia had a significantly positive prediction effect on mobile phone addiction, and depression, anxiety, and stress on mobile phone are positive predictors. Depression, anxiety or stress had partially mediating effects between alexithymia and mobile phone addiction. Alexithymia not only directly had a positively impact on mobile phone addiction, but both also had an indirect effect on mobile phone addiction through depression, anxiety or stress.
Limitations:
Limitations included sampling method and modest sample size, self-report measures, and unmeasured potential confounders.
Conclusion:
Alexithymia is an important correlate of mobile phone addiction, and depression, anxiety or stress is an important mediator in this relationship.
Background:
The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior.
Methods:
C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed.
Results:
Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota.
Conclusions:
Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology.
Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment. These data, together with a wealth of reports using different animal models with depression-like behavior or manipulation of expression of BDNF or its receptor TrkB have implicated BDNF in the pathophysiology of depression as well as in the mechanism of action of antidepressant treatments. Recent findings have shown that posttranslational processing of BDNF gene product can yield different molecular entities that differently influence signaling through BNDF receptor TrkB and the pan-neurotrophin receptor p75(NTR). We will here review these data and discuss new insights into the possible pathophysiological roles of those new BDNF subtypes as well as recent findings on the role of BDNF mediated neuronal plasticity in mood disorders and their treatments.