Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies.

Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis.

BACKGROUND: Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear. PURPOSE: This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA. METHODS: Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT). RESULTS: LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA. CONCLUSION: The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.

Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis.

The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 µg/L) and RIS (0.03 and 3 µg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.

Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis.

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

Phyllanthus emblica Fruit Improves Obesity by Reducing Appetite and Enhancing Mucosal Homeostasis via the Gut Microbiota-Brain-Liver Axis in HFD-Induced Leptin-Resistant Rats.

The impact of leptin resistance on intestinal mucosal barrier integrity, appetite regulation, and hepatic lipid metabolism through the microbiota-gut-brain-liver axis has yet to be determined. Water extract of Phyllanthus emblica L. fruit (WEPE) and its bioactive compound gallic acid (GA) effectively alleviated methylglyoxal (MG)-triggered leptin resistance in vitro. Therefore, this study investigated how WEPE and GA intervention relieve leptin resistance-associated dysfunction in the intestinal mucosa, appetite, and lipid accumulation through the microbiota-gut-brain-liver axis in high-fat diet (HFD)-fed rats. The results showed that WEPE and GA significantly reduced tissues (jejunum, brain, and liver) MG-evoked leptin resistance, malondialdehyde (MDA), proinflammatory cytokines, SOCS3, orexigenic neuropeptides, and lipid accumulation through increasing leptin receptor, tight junction proteins, antimicrobial peptides, anorexigenic neuropeptides, excretion of fecal triglyceride (TG), and short-chain fatty acids (SCFAs) via a positive correlation with the Allobaculum and Bifidobacterium microbiota. These novel findings suggest that WEPE holds the potential as a functional food ingredient for alleviating obesity and its complications.

Long-term use of etomidate disrupts the intestinal homeostasis and nervous system in mice.

Etomidate (ETO) is used as an anesthetic in surgery, but it is being abused in some populations. The damage caused by long-term intake of ETO to intestinal and brain functions is not yet clear, and it remains to be determined whether the drug affects the central nervous system through the gut-brain axis. This study aimed to investigate the neurotoxic and gastrointestinal effects of ETO at doses of 1 mg/kg and 3 mg/kg in mice over 14 consecutive days. The results showed that long-term injection of ETO led to drug resistance in mice, affecting their innate preference for darkness and possibly inducing dependence on ETO. The levels of 5-hydroxytryptamine in the brain, serum, and colon decreased by 37%, 51%, and 42% respectively, while the levels of γ-aminobutyric acid reduced by 38%, 52%, and 41% respectively. H&E staining revealed that ETO reduced goblet cells in the colon and damaged the intestinal barrier. The expression of tight junction-related genes Claudin4 and ZO-1 was downregulated. The intestinal flora changed, the abundance of Akkermansia and Lactobacillus decreased by 33% and 14%, respectively, while Klebsiella increased by 18%. TUNEL results showed that high-dose ETO increased apoptotic cells in the brain. The expression of Claudin1 in the brain was downregulated. Untargeted metabolomics analysis of the colon and brain indicated that ETO caused abnormalities in glycerophospholipid metabolism. Abnormal lipid metabolism might lead to the production or accumulation of lipotoxic metabolites, causing central nervous system diseases. ETO induced changes in the intestinal flora and metabolism, further affecting the central nervous system through the gut-brain axis. The study unveiled the detrimental effects on the brain and gastrointestinal system resulting from long-term intake of ETO, which holds significant implications for comprehending the adverse impact of ETO abuse on human health.

Enrofloxacin exposure undermines gut health and disrupts neurotransmitters along the microbiota-gut-brain axis in zebrafish.

The environmental prevalence of antibiotic residues poses a potential threat to gut health and may thereby disrupt brain function through the microbiota-gut-brain axis. However, little is currently known about the impacts of antibiotics on gut health and neurotransmitters along the microbiota-gut-brain axis in fish species. Taking enrofloxacin (ENR) as a representative, the impacts of antibiotic exposure on the gut structural integrity, intestinal microenvironment, and neurotransmitters along the microbiota-gut-brain axis were evaluated in zebrafish in this study. Data obtained demonstrated that exposure of zebrafish to 28-day environmentally realistic levels of ENR (6 and 60 µg/L) generally resulted in marked elevation of two intestinal integrity biomarkers (diamine oxidase (DAO) and malondialdehyde (MDA), upregulation of genes that encode inter-epithelial tight junction proteins, and histological alterations in gut as well as increase of lipopolysaccharide (LPS) in plasma, indicating an evident impairment of the structural integrity of gut. Moreover, in addition to significantly altered neurotransmitters, markedly higher levels of LPS while less amount of two short-chain fatty acids (SCFAs), namely acetic acid and valeric acid, were detected in the gut of ENR-exposed zebrafish, suggesting a disruption of gut microenvironment upon ENR exposure. Along with corresponding changes detected in gut, significant disruption of neurotransmitters in brain indicated by marked alterations in the contents of neurotransmitters, the activity of acetylcholin esterase (AChE), and the expression of neurotransmitter-related genes were also observed. These findings suggest exposure to environmental antibiotic residues may impair gut health and disrupt neurotransmitters along the microbiota-gut-brain axis in zebrafish. Considering the prevalence of antibiotic residues in environments and the high homology of zebrafish to other vertebrates including human, the risk of antibiotic exposure to the health of wild animals as well as human deserves more attention.

The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.

Steering the Microbiota-Gut-Brain Axis by Antibiotics to Model Neuro-Immune-Endocrine Disorders.

BACKGROUND: Over the last century, animal models have been employed to study the gut-brain axis and its relationship with physiological processes, including those necessary for survival, such as food intake and thermoregulation; those involved in diseases, ranging from inflammation to obesity; and those concerning the development of neurodegenerative diseases and neuropsychiatric disorders, such as Alzheimer's disease and autism spectrum disorder, respectively. SUMMARY: The gut microbiota has been recognized in the last decade as an essential functional component of this axis. Many reports demonstrate that the gut microbiota influences the development of a vast array of physiological processes. Experiments that use animal models to assess the effect of the gut microbiota on the brain and behavior may involve the acute or chronic administration of broad-spectrum antibiotics. KEY MESSAGES: This narrative review summarizes the beneficial or detrimental effects of antibiotics administered prenatally or postnatally to rodents during acute or chronic periods in a wide range of protocols. These include animal models of disease and behavioral paradigms of learning and memory, anxiety, obsessive-compulsive disorder, and autism spectrum disorder. Biomarkers and behavioral assays associated with antibiotic exposure are also included in this review.

Berberine alleviates Alzheimer's disease by regulating the gut microenvironment, restoring the gut barrier and brain-gut axis balance.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Intestinal flora and its metabolism play a significant role in ameliorating central nervous system disorders, including AD, through bidirectional interactions between the gut-brain axis. A naturally occurring alkaloid compound called berberine (BBR) has neuroprotective properties and prevents Aß-induced microglial activation. Additionally, BBR can suppress the synthesis of Aß and decrease BACE1 expression. However, it is still unclear if BBR therapy can alleviate AD by changing the gut flora. PURPOSE: In this study, we examined whether a partial alleviation of AD could be achieved with BBR treatment and the molecular mechanisms involved. METHODS: We did this by analyzing alterations in Aß plaques, neurons, and related neuroinflammation-related markers in the brain and the transcriptome of the mouse brain. The relationship between the intestinal flora of 5xFAD model mice and BBR treatment was investigated using high-throughput sequencing analysis of 16S rRNA from mouse feces. RESULTS: The findings demonstrated that treatment with BBR cleared Aß plaques, alleviated neuroinflammation, and ameliorated spatial memory dysfunction in AD. BBR significantly alleviated intestinal inflammation, decreased intestinal permeability, and could improve intestinal microbiota composition in 5xFAD mice.

The microbiota-gut-brain axis: A crucial immunomodulatory pathway for Bifidobacterium animalis subsp. lactis' resilience against LPS treatment in neonatal rats.

An imbalanced gut microflora may contribute to immune disorders in neonates due to an immature gut barrier. Bacterial toxins, particularly, can trigger the immune system, potentially resulting in uncontrolled gut and systemic inflammation. Previous research has revealed that Bifidobacterium animalis subsp. lactis (B. lactis) could protect against early-life pathogen infections by enhancing the gut barrier. However, the effects of B. lactis on a compromised immune system remain uncertain. Hence, this study concentrated on the immunomodulatory effects and mechanisms of B. lactis in neonatal rats intraperitoneally injected with lipopolysaccharide (LPS), a bacterial toxin and inflammatory mediator. First, B. lactis significantly alleviated the adverse effects induced by LPS on the growth, development, and body temperature of neonatal rats. Second, B. lactis significantly reduced the immune responses and damage induced by LPS, affecting both systemic and local immune responses in the peripheral blood, gut, and brain. Notably, B. lactis exhibited extra potent neuroprotective and neurorepair effects. Our research found that pre-treatment with B. lactis shaped the diverse gut microecology by altering both microbial populations and metabolic biomolecules, closely linked to immunomodulation. Overall, this study elucidated the multifaceted roles of B. lactis in neonatal hosts against pathogenic infection and immune disorder, revealing the existence of the microbiota-gut-brain axis.

Notoginsenoside R1 alleviates cerebral ischemia/reperfusion injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway through microbiota-gut-brain axis.

BACKGROUND: Ischemic stroke (IS) ranks as the second common cause of death worldwide. However, a narrow thrombolysis timeframe and ischemia-reperfusion (I/R) injury limits patient recovery. Moreover, anticoagulation and antithrombotic drugs do not meet the clinical requirements. Studies have demonstrated close communication between the brain and gut microbiota in IS. Notoginsenoside R1 (NG-R1), a significant component of the total saponins from Panax notoginseng, has been demonstrated to be effective against cerebral I/R injury. Total saponins have been used to treat IS in Chinese pharmacopoeia. Furthermore, previous research has indicated that the absorption of NG-R1 was controlled by gut microbiota. STUDY DESIGN: This study aimed to access the impact of NG-R1 treatment on neuroinflammation and investigate the microbiota-related mechanisms. RESULTS: NG-R1 significantly reduced neuronal death and neuroinflammation in middle cerebral artery occlusion/reperfusion (MCAO/R) models. 16S rRNA sequencing revealed that NG-R1 treatment displayed the reversal of microbiota related with MCAO/R models. Additionally, NG-R1 administration attenuated intestinal inflammation, gut barrier destruction, and systemic inflammation. Furthermore, microbiota transplantation from NG-R1 exhibited a similar effect in the MCAO/R models. CONCLUSION: In summary, NG-R1 treatment resulted in the restoration of the structure of the blood-brain barrier (BBB) and reduction in neuroinflammation via suppressing the stimulation of astrocytes and microglia in the cerebral ischemic area. Mechanistic research demonstrated that NG-R1 treatment suppressed the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) signaling pathway in both the ischemic brain and colon. NG-R1 treatment enhanced microbiota dysbiosis by inhibiting the TLR4 signaling pathway to protect MCAO/R models. These findings elucidate the mechanisms by which NG-R1 improve stroke outcomes and provide some basis for Panax notoginseng saponins in clinical treatment.

Exploring environmental exposomes and the gut-brain nexus: Unveiling the impact of pesticide exposure.

This review delves into the escalating concern of environmental pollutants and their profound impact on human health in the context of the modern surge in global diseases. The utilisation of chemicals in food production, which results in residues in food, has emerged as a major concern nowadays. By exploring the intricate relationship between environmental pollutants and gut microbiota, the study reveals a dynamic bidirectional interplay, as modifying microbiota profile influences metabolic pathways and subsequent brain functions. This review will first provide an overview of potential exposomes and their effect to gut health. This paper is then emphasis the connection of gut brain function by analysing microbiome markers with neurotoxicity responses. We then take pesticide as example of exposome to elucidate their influence to biomarkers biosynthesis pathways and subsequent brain functions. The interconnection between neuroendocrine and neuromodulators elements and the gut-brain axis emerges as a pivotal factor in regulating mental health and brain development. Thus, manipulation of gut microbiota function at the onset of stress may offer a potential avenue for the prevention and treatment for mental disorder and other neurodegenerative illness.

Suanzaoren decoction improves depressive-like behaviors by regulating the microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 inflammation signal pathway.

Depression is a common but serious sickness which causes a considerable burden on individuals and society. Recently, it has been well established that the occurrence of depression was related to the microbiota-gut-brain axis. The toll-like receptor 4 (TLR4)/ nuclear factor kappa-B kinase (NFκB)/ NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway is closely associated with the regulation of microbiota-gut-brain axis. Suanzaoren Decoction (SZRD), which recorded in Jin Gui Yao Lve in Han dynasty, has been used for treating insomnia and depression for a long time. However, the action mechanism of the depression regulation through the TLR4/NFκB/NLRP3 pathway by SZRD was still unclear. In this study, SZRD was firstly performed on a chronic unpredictable mild stress (CUMS) mice model. The results of behavioral tests showed that SZRD treatment could ameliorate the depressive-like behaviors of CUMS mice effectively. According to our previous researches about the components of SZRD in vitro and in vivo, the identification of serum metabolites in depression model rats was further analyzed qualitatively using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry. 27 prototypes and 44 metabolites were identified. The main types of metabolic reactions are glucuronization, sulfation, and so on. Then, using immunohistochemistry and western blotting to monitor the difference in activation of TLR4/NFκB/NLRP3 signaling pathway in mice brain and colon. The results showed that SZRD treatment could reduce expression levels of related factors. Additionally, the SZRD treatment could also inhibit the histopathological damage in the path morphology of the hippocampus and colon. The results of 16SrRNA demonstrated that SZRD could reduce the dysbiosis of the intestinal flora of depressive mice. The above results provided important information for studying the action mechanism of SZRD in treating depression by regulating microbiota-gut-brain axis via inhibiting TLR4/NFκB/NLRP3 pathway.

Secretin modulates appetite via brown adipose tissue-brain axis.

PURPOSE: Secretin activates brown adipose tissue (BAT) and induces satiation in both mice and humans. However, the exact brain mechanism of this satiety inducing, secretin-mediated gut-BAT-brain axis is largely unknown. METHODS AND RESULTS: In this placebo-controlled, single-blinded neuroimaging study, firstly using [18F]-fluorodeoxyglucose (FDG) PET measures (n = 15), we established that secretin modulated brain glucose consumption through the BAT-brain axis. Predominantly, we found that BAT and caudate glucose uptake levels were negatively correlated (r = -0.54, p = 0.037) during secretin but not placebo condition. Then, using functional magnetic resonance imaging (fMRI; n = 14), we found that secretin improved inhibitory control and downregulated the brain response to appetizing food images. Finally, in a PET-fMRI fusion analysis (n = 10), we disclosed the patterned correspondence between caudate glucose uptake and neuroactivity to reward and inhibition, showing that the secretin-induced neurometabolic coupling patterns promoted satiation. CONCLUSION: These findings suggest that secretin may modulate the BAT-brain metabolic crosstalk and subsequently the neurometabolic coupling to induce satiation. The study advances our understanding of the secretin signaling in motivated eating behavior and highlights the potential role of secretin in treating eating disorders and obesity. TRIAL REGISTRATION: EudraCT no. 2016-002373-35, registered 2 June 2016; Clinical Trials no. NCT03290846, registered 25 September 2017.

Prenatal exposure to titanium dioxide nanoparticles induces persistent neurobehavioral impairments in maternal mice that is associated with microbiota-gut-brain axis.

Gestational exposure to titanium dioxide nanoparticles (TiO2NPs) has been widely reported to have deleterious effects on the brain functions of offspring. However, little attention has been paid to the neurotoxic effects of TiO2NPs on maternal body after parturition. The pregnant mice were orally administrated with TiO2NPs at 150 mg/kg from gestational day 8-21. The potential effects of TiO2NPs on the neurobehaviors were evaluated at postnatal day 60. The gut microbiota, morphological alterations of intestine and brain, and other indicators that involved in gut-brain axis were all assessed to investigate the underlying mechanisms. The results demonstrated that exposure to TiO2NPs during pregnancy caused the persistent neurobehavioral impairments of maternal mice after delivery for 60 days, mainly including behavioural changes, pathological changes in hippocampus, cortex and intestine. Our data also showed that persistent dysfunction and tissue injuries were probably associated with the disruption of gut-brain axis, manifested by the shift in the composition of gut microbial community, alteration of Sstr1, inhibition of enteric neurons and reduction of diamine oxidase contents in maternal mice. These findings provide a novel insight that regulation of gut microecology may be an alternative strategy for the protection against the neurotoxicity of TiO2NPs in pregnant women.

The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems.

Altered gut-brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.

How Microbes Affect Depression: Underlying Mechanisms via the Gut-Brain Axis and the Modulating Role of Probiotics.

Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut-brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known to contribute to the up-regulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis causes decreased levels of BDNF, which could affect neuronal development and synaptic plasticity. Increased gut permeability causes an influx of gut microbial components such as lipopolysaccharides, and the resultant systemic inflammation may lead to neuroinflammation in the central nervous system. In light of the fact that gut microbial factors contribute to the initiation and exacerbation of depressive symptoms, this review summarizes the current understanding of the molecular mechanisms involved in MDD onset, and discusses the therapeutic potential of probiotics, including butyrate-producing bacteria, which can mediate the microbiota-gut-brain axis.

Centenarian-Sourced Lactobacillus casei Combined with Dietary Fiber Complex Ameliorates Brain and Gut Function in Aged Mice.

Dietary intervention could modulate age-related neurological disorders via the gut-brain axis. The potential roles of a probiotic and the dietary fiber complex (DFC) on brain and gut function in aged mice were investigated in this study. Lactobacillus casei LTL1361 and DFC were orally administrated for 12 weeks, and the learning and memory ability, as well as the oxidative parameters, inflammatory markers, gut barrier function and microbial metabolite short-chain fatty acids (SCFAs), were investigated. LTL1361 and DFC supplementation ameliorated cognitive ability, attenuated oxidative stress in brain and inflammation in serum and colon, ameliorated gut barrier function, and increased the SCFA concentrations and gene expression of SCFA receptors. The protective effect was more significantly enhanced in aged mice treated with the combination of LTL1361 and DFC than treated with LTL1361 or DFC alone. These results could be associated with the protected morphology of pyramidal nerve cells in hippocampus of mice brain and the downregulation of apoptosis marker caspase-3 in brain and upregulation of tight junction proteins in small intestine and colon. The results indicated that Lactobacillus casei LTL1361 and DFC alleviated age-related cognitive impairment, as well as protected brain and gut function. Lactobacillus casei LTL1361 and DFC might be used as novel and promising antiaging agents in human.