Brain-gut Peptide Research Articles

Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.

The combination of a glucagon-like peptide-1 and amylin receptor agonists reduces alcohol consumption in both male and female rats.

Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 may be of potential interest as they individually reduce alcohol intake in rodents. While the combination of amylin receptor (AMYR) and glucagon-like peptide-1 receptor (GLP-1R) agonists have been found to decrease feeding and body weight in obese male rats synergistically, their combined impact on alcohol intake is unknown. Therefore, the effect of the combination of an AMYR (salmon calcitonin (sCT)) and a GLP-1R (dulaglutide) agonist on alcohol intake in rats of both sexes was explored in two separate alcohol-drinking experiments. The first alcohol-drinking experiment evaluated the potential of adding sCT to an ongoing dulaglutide treatment, whereas the second alcohol-drinking experiment examined the effect when adding sCT and dulaglutide simultaneously. When adding sCT to an ongoing dulaglutide treatment, a reduction in alcohol intake was observed in both male and female rats. However, when combining sCT and dulaglutide simultaneously, an initial reduction in alcohol intake was observed in rats of both sexes, whereas tolerance towards treatment was observed. In both alcohol-drinking experiments, this treatment combination consistently decreased food consumption and body weight in males and females. While the treatment combination did not affect inflammatory mediators, the gene expression of AMYR or GLP-1R, it changed fat tissue morphology. Further investigation needs to be done on the combination of AMYR and GLP-1R agonists to assess their combined effects on alcohol intake.

Weichang' an pill alleviates functional dyspepsia through modulating brain-gut peptides and gut microbiota.

To evaluate the effect of Weichang'an pill (, WCAP) on functional dyspepsia (FD) and explore its regulation of brain-gut peptides (BGPs) and gut microbiota balance as a potential treatment mechanism. The "0 ℃ saline gavage + irregular feeding and tail clamp" method was used to establish the FD rat model, excluding the normal group. The successfully established FD rat models were randomly divided into the model group and the WCAP1 (WC1), WCAP2 (WC2), WCAP3 (WC3), WCAP4 (WC4), WCAP5 (WC5), and Domperidone (Dom) groups (n = 10 per group). The unhandled rats were designated as the control group. The gastrointestinal motility of the rats was evaluated using the charcoal propulsion test. Histopathology was assessed by hematoxylin and eosin (HE) staining. The enzyme-linked immunosorbnent assay method was used to detect the levels of motilin (MTL), gastrin (GAS), vasoactive intestinal peptide (VIP), and somatostatin (SS) in the serum from each group. In addition, the gut microbiota composition of fecal samples was analyzed using 16S rRNA sequencing. Rat models were successfully established according to data from rat state, gastrointestinal motility assessments, and HE staining. WCAP improved FD symptoms by accelerating the gastric emptying and small intestinal transit of FD rats. Mechanistically, WCAP increased the levels of GAS and MTL and reduced the levels of VIP and SS. Moreover, WCAP treatment restored the total relative abundance of Firmicutes and Bacteroidetes, increased the species richness of the gut flora, and modulated the changes in the composition and function of the gut microbiota. WCAP can effectively promote the recovery of gastrointestinal motility disorders in FD rats. The mechanism may be related to regulating the secretion of BGPs and the composition of the gut microbiota.

Hesperidin facilitating gastrointestinal motility by “Gut-brain axis” and “SCF/C-Kit signaling pathways”

Hesperidin shows promising results as a potential feed additive for enhancing gastrointestinal motility in animals. Gastrointestinal function plays a pivotal role in animal growth and the digestibility of dietary nutrients, with gastrointestinal motor function serving as a crucial component. However, limited research has been conducted on the application of hesperidin as a feed additive to promote gastrointestinal motility. The present study aims to assess the efficacy of Hesperidin as a feed additive in promoting gastrointestinal motility and elucidating its underlying mechanism. A total of 200 newly hatched (1-day-old) broilers with similar body weight were randomly allocated into 4 groups as follows: the control group receiving only the basal diet, and the other 3 groups supplemented with 50, 100, and 150 mg of hesperidin per kg of the basal diet, respectively. Each group consisted of 5 replicates with ten broilers per replicate, and the feeding trial lasted for a duration of 21 d. At 21 d of age, a 5% w/v Evans Blue solution in distilled water was utilized to measure intestinal transit rates (ITR). Gastric emptying (GE) was evaluated by administering a phenol red solution at a concentration of 0.05% w/v (1 mL/broiler). Fifteen broilers from each group were euthanized and immediately dissected to obtain gizzard, hypothalamus, duodenum, and jugular blood samples. Jugular blood samples were collected for brain-gut peptide content analysis, while gizzard, hypothalamus, and duodenum samples were used for immunohistochemical analysis. Real-time qPCR was performed on gizzard samples. The results demonstrated a significant improvement in the GE and ITR of broilers in all treatment groups compared to the control group (P < 0.05), particularly in the 100mg/Kg and 150mg/Kg hesperidin group. Incorporation of hesperidin into the broilers' diet significantly enhances serum levels of ghrelin, encompassing serotonin (5-HT), motilin (MTL), cholecystokinin (CCK), and Stem Cell Factor (SCF) as well as substance P (SP) in the gizzard and duodenal tissues while reducing vasoactive intestinal peptide (VIP) levels (P < 0.05). The group administered a dosage of 150mg/Kg exhibited the most pronounced effect.Immunohistochemistry analysis revealed that hesperidin supplementation up-regulated SP protein content and down-regulated VIP protein content in the hypothalamus, gizzard, and duodenum of broilers (P < 0.05), with the most pronounced effect illustrated in the 150mg/Kg hesperidin group. Furthermore, addition of hesperidin to broiler feed resulted in a significant up-regulation of protein expression and gene expression related to SCF and The protein expression of Receptor tyrosine kinase (C-Kit) was significantly upregulated in the 150mg/Kg group, while the gene expression of C-Kit was significantly upregulated in the 50 mg/Kg group (P < 0.05). In conclusion, hesperidin exhibits promising potential as a feed additive for broilers, as its dietary supplementation of hesperidin improves gastrointestinal motility through modulation of both "gut-brain axis" signaling pathways and "SCF/C-Kit signaling pathways" within broiler chicken's digestive system. Notably, basal diet supplemented with 150mg/Kg hesperidin demonstrates superior efficacy.

LEAP2, a ghrelin receptor inverse agonist, and its effect on alcohol-related responses in rodents

The underlying neurobiology of alcohol use disorder (AUD) is complex and needs further unraveling, with one of the key mechanisms being the gut-brain peptide ghrelin and its receptor (GHSR). However, additional substrates of the ghrelin pathway, such as liver-expressed antimicrobial peptide 2 (LEAP2), an endogenous GHSR inverse agonist, may contribute to this neurobiological framework. While LEAP2 modulates feeding and reward through central mechanisms, its effects on alcohol responses are unknown. The aim of the present study was therefore to identify the impact of central LEAP2 on the ability of alcohol to activate the mesolimbic dopamine system and to define its ability to control alcohol intake. These experiments revealed that central LEAP2 (i.e. into the third ventricle) prevented the ability of alcohol to cause locomotor stimulation in male mice, suppressed the memory of alcohol reward and attenuated the dopamine release in the nucleus accumbens caused by alcohol. Moreover, central LEAP2 reduced alcohol consumption in both male and female rats exposed to alcohol for 6 weeks before treatment. However, the serum levels of LEAP2 were similar between high- and low- alcohol-consuming (male) rats. Furthermore, central LEAP2 lowered the food intake in the alcohol-consuming male rats and reduced the body weight in the females. Collectively, the present study revealed that central LEAP2 mitigates alcohol-related responses in rodents, contributing to our understanding of the ghrelin pathway’s role in alcohol effects.

Clinical effect of the warm acupuncture of Mongolian medicine on insomnia in the elderly and its brain-gut peptide mechanism: a randomized controlled trial

To observe the clinical effect and safety of the warm acupuncture of Mongolian medicine in treatment of insomnia in the elderly, and to explore its underlying brain-gut peptide mechanism. Sixty elderly patients with insomnia were randomly divided into a warm acupuncture group and a western medication group, 30 cases in each group. In the warm acupuncture group, the warm acupuncture of Mongolian medicine was operated at Dinghuixue (at the center of the vertex, the crossing site of the anterior midline and the line connected the upper edges of two ear apexes), Heyixue (at the depression of the spinous process of the 7th cervical vertebra) or Xinxue (at the depression of the spinous process of the 6th thoracic vertebra) in each treatment. Only one of the above points was selected and stimulated for 20 min one treatment and the three points were used alternatively. The treatment was given once every day or every other day, 3 times a week, and for a total of 3 weeks. In the western medication group, estazolam tablets were administered orally, once a day, 1 mg before bedtime, consecutively for 3 weeks. Before and after treatment, as well as in 1-month follow-up visit after the treatment completion, the scores of the Pittsburgh sleep quality index (PSQI) and the insomnia severity index (ISI) were observed in the two groups. The serum brain-related peptide markers (substance P [SP], neuropeptide Y [NPY], 5-hydroxytryptamine 1A [5-HT1A] and 5-hydroxytryptamine 2A [5-HT2A]) were measured before and after treatment, and the clinical efficacy and safety was evaluated in the two groups. After treatment and in follow-up, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total scores of PSQI, and ISI scores were all reduced in the two groups (P<0.05, P<0.01); and the scores in the warm acupuncture group were lower than those of the western medication group (P<0.05, P<0.01). After treatment, the levels of serum SP and 5-HT2A were decreased (P<0.01) and the levels of serum NPY and 5-HT1A were increased (P<0.01) when compared with those before treatment in the two groups. The levels of serum SP and 5-HT2A in the warm acupuncture group were lower than those of the western medication group (P<0.05), and the levels of serum NPY and 5-HT1A were higher than those of the western medication group (P<0.05). After treatment, the total effective rate was 93.3% (28/30) in the warm acupuncture group, which was higher than 83.3% (25/30) of the western medication group (P<0.05). No serious adverse reactions were found in the two groups. Warm acupuncture of Mongolian medicine can effectively improve the sleep quality of the elderly patients with insomnia, and its mechanism may be related to the regulation of the levels of serum SP, NPY, 5-HT1A and 5-HT2A.

Nucleus accumbens ghrelin signaling controls anxiety-like behavioral response to acute stress

BackgroundAnxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated.MethodsIn the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests.ResultsWe reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects.ConclusionsThis study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.

Improvement of functional dyspepsia with Suaeda salsa (L.) Pall via regulating brain-gut peptide and gut microbiota structure.

The traditional Chinese herbal medicine Suaeda salsa (L.) Pall (S. salsa) with a digesting food effect was taken as the research object, and its chemical composition and action mechanism were explored. The chemical constituents of S. salsa were isolated and purified by column chromatography, and their structures were characterized by nuclear magnetic resonance. The food accumulation model in mice was established, and the changes of the aqueous extract of S. salsa in gastric emptying and intestinal propulsion rate, colonic tissue lesions, serum brain-gut peptide hormone, colonic tissue protein expression, and gut microbiota structure were compared. Ten compounds were isolated from S. salsa named as naringenin (1), hesperetin (2), baicalein (3), luteolin (4), isorhamnetin (5), taxifolin (6), isorhamnetin-3-O-β-D-glucoside (7), luteolin-3'-D-glucuronide (8), luteolin-7-O-β-D-glucuronide (9), and quercetin-3-O-β-D-glucuronide (10), respectively. The aqueous extract of S. salsa can improve the pathological changes of the mice colon and intestinal peristalsis by increasing the rate of gastric emptying and intestinal propulsion. By adjusting the levels of 5-HT, CCK, NT, SS, VIP, GT-17, CHE, MTL, and ghrelin, it can upregulate the levels of c-kit, SCF, and GHRL protein, and restore the imbalanced structure of gut microbiota, further achieve the purpose of treating the syndrome of indigestion. The effect is better with the increase of dose. S. salsa has a certain therapeutic effect on mice with the syndrome of indigestion. From the perspective of "brain-gut-gut microbiota", the mechanism of digestion and accumulation of S. salsa was discussed for the first time, which provided an experimental basis for further exploring the material basis of S. salsa.

Decoding the influence of central LEAP2 on food intake and its effect on accumbal dopamine release

The gut-brain peptide ghrelin and its receptor are established as a regulator of hunger and reward-processing. However, the recently recognized ghrelin receptor inverse agonist, liver-expressed antimicrobial peptide 2 (LEAP2), is less characterized. The present study aimed to elucidate LEAP2s central effect on reward-related behaviors through feeding and its mechanism. LEAP2 was administrated centrally in mice and effectively reduced feeding and intake of palatable foods. Strikingly, LEAP2s effect on feeding was correlated to the preference of the palatable food. Further, LEAP2 reduced the rewarding memory of high preference foods, and attenuated the accumbal dopamine release associated with palatable food exposure and eating. Interestingly, LEAP2 was widely expressed in the brain, and particularly in reward-related brain areas such as the laterodorsal tegmental area (LDTg). This expression was markedly altered when allowed free access to palatable foods. Accordingly, infusion of LEAP2 into LDTg was sufficient to transiently reduce acute palatable food intake. Taken together, the present results show that central LEAP2 has a profound effect on dopaminergic reward signaling associated with food and affects several aspects of feeding. The present study highlights LEAP2s effect on reward, which may have applications for obesity and other reward-related psychiatric and neurological disorders.

Diversity of the Ghrelin Gene in Nigeria’s Fulani and Yoruba Ecotype Chickens

Ghrelin (GHRL) is a novel 28-amino acid gut-brain peptide linked to a gene associated with the regulation of growth hormones in birds. This study was carried out to investigate the polymorphism of the Ghrelin gene in Fulani and Yoruba ecotypes chickens in Nigeria. Blood samples were collected from seventy-eight (78) Nigerian indigenous chickens comprising of 41 Yoruba ecotype chickens and 37 Fulani ecotype chickens. Polymerase Chain Reaction-Restriction fragment length polymorphism (PCR-RFLP) method was used and the MboII restriction enzyme cut site 71 of the ghrelin and genetic structure were determined. Population structure was analyzed using allele and genotype frequencies, heterozygosity and genetic variation metrics. Two alleles (C and T) and three genotypes (CC, CT and TT) were observed. In the Yoruba Ecotype, the allele frequencies were C (0.34) and T (0.66) respectively while C (0.45) and T (0.55) were observed in the Fulani ecotype and the overall population was C (0.39) and T (0.61). The genotype frequencies obtained were; in the Yoruba ecotype, CC (0.10), CT (0.48), and TT (0.41) were observed. In the Fulani ecotype, CC (0.22), CT (0.45), and TT (0.32) were also observed, and in the overall population CC (0.15). CT (0.47) and TT (0.37) were observed. FIS values for the Yoruba ecotype (-0.0847) and Fulani ecotype (0.00702) reflects random mating and inbreeding respectively. The effective number of alleles indicates that the Fulani ecotype has more effective alleles compared to the Yoruba ecotype. These results suggest that the Yoruba ecotype may be at Hardy-Weinberg equilibrium, while Fulani ecotype deviates for the ghrelin locus. In summary, our results may open opportunities for genetic improvement in Nigerian indigenous chicken due to the polymorphic nature of the ghrelin gene.

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea

Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. Methods: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. Results: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. Conclusion: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases.

Dopamine (DA) is a neurotransmitter synthesized in the human body that acts on multiple organs throughout the body, reaching them through the blood circulation. Neurotransmitters are special molecules that act as messengers by binding to receptors at chemical synapses between neurons. As ligands, they mainly bind to corresponding receptors on central or peripheral tissue cells. Signalling through chemical synapses is involved in regulating the activities of various body systems. Lack of DA or a decrease in DA levels in the brain can lead to serious diseases such as Parkinson's disease, schizophrenia, addiction and attention deficit disorder. It is widely recognized that DA is closely related to neurological diseases. As research on the roles of brain-gut peptides in human physiology and pathology has deepened in recent years, the regulatory role of neurotransmitters in digestive system diseases has gradually attracted researchers' attention, and research on DA has expanded to the field of digestive system diseases. This review mainly elaborates on the research progress on the roles of DA and DRs related to digestive system diseases. Starting from the biochemical and pharmacological properties of DA and DRs, it discusses the therapeutic value of DA- and DR-related drugs for digestive system diseases.

GW9508 ameliorates cognitive dysfunction via autophagy pathway in streptozotocin-induced mouse model of Alzheimer's disease.

G protein-coupled receptor 40 (GPR40) is a potential drug target for Alzheimer's disease (AD), and its agonist GW9508 ameliorates cognitive impairment by intravenous administration. The present study was conducted to investigate the efficacy of GW9508 administered peripherally on cognitive dysfunction in streptozotocin (STZ)-induced AD mice. Seventy male ICR mice were randomly divided into seven groups: vehicle sham group, model, Donepezil, GW9508-L, GW9508-M, GW9508-H, and GW1100 + GW9508-H groups, and administered either vehicle (artificial cerebrospinal fluid [aCSF]) or STZ (3mg/kg in the vehicle) once a day (9:00 a.m.) by intracerebroventricular injection bilaterally on day 1 and day 3, respectively. After 2weeks of recovery, all mice were given drug treatment. Behavioral experiments were applied to test the recognition and spatial memory of mice, while molecular biology experiments such as Western blot, ELISA, and Nissl staining were used to detect the corresponding changes of signaling pathways. Intraperitoneal administration of GW9508 prevented STZ-induced cognitive impairment as well as decreased the level of p-tau and Aβ1-42 in plasma and brain. GW9508 upregulated the expression of gut-brain peptides like PYY, CCK, IGF-1, and GLP-1 both in blood circulation and brain and downregulated the expression level of autophagy-related proteins through activating Akt/mTOR signaling pathway. Meanwhile, the treatment effect of GW9508 was reversed by GPR40 antagonist GW1100 significantly. Peripheral administration of GW9508 exhibits neuroprotective effects, and it could be a promising therapy for AD. The neuroprotective mechanism of GW9508 was based on promoting gut-brain peptide secretion, activating Akt/mTOR signal pathway, and regulating neuronal autophagy.

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

BackgroundGut 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. PurposeThis 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. MethodsKey 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). ResultsLBRD 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. ConclusionThe 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.

Multiomics and blood-based biomarkers of moyamoya disease: protocol of Moyamoya Omics Atlas (MOYAOMICS)

BackgroundMoyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies.MethodsThe MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients.ConclusionsThe MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Podophyllotoxin-mediated neurotoxicity via the microbiota-gut-brain axis in SD rats based on the toxicological evidence chain (TEC) concept

Podophyllotoxin (PPT) is a naturally occurring aryltetralin lignan. However, its clinical application has been limited due to its neurotoxicity, the mechanism of which remains unclear. This study aimed to investigate the potential involvement of the microbiota-gut-brain (MGB) axis in PPT-induced neurotoxicity using the toxicological evidence chain concept. Our approach included behavioral testing in rats, evaluation of colon and hippocampal pathological changes, examination of proinflammatory factors, brain-gut peptides, and an in-depth analysis of gut microbiome and metabolic profiles. Our results demonstrated that PPT exposure compromised cognitive functions, induced damage to the colon and hippocampus, and increased intestinal permeability in rats. Furthermore, it elevated proinflammatory factors, particularly TNF-α and IL-6, while causing disruptions in the gut microbiota, favoring Escherichia-Shigella over Lactobacillus. Significant alterations in metabolic profiles in feces, serum, and hippocampus, particularly in tryptophan metabolism with a correlation to inflammatory factors and Escherichia-Shigella, were also observed. Our findings suggest that PPT promotes the enrichment of Escherichia-Shigella leading to inflammatory factor production and alterations in kynurenine metabolism in the hippocampus, potentially contributing to neurotoxicity. The study provides novel insights into the mechanistic pathways of PPT-induced neurotoxicity, emphasizing the role of the MGB axis and offering avenues for therapeutic interventions.

Role and molecular mechanism of ghrelin in degenerative musculoskeletal disorders.

Ghrelin is a brain-gut peptide, and the first 28-peptide that was found in the gastric mucosa. It has a growth hormone (GH)-releasing hormone-like effect and can potently promote the release of GH from pituitary GH cells; however, it is unable to stimulate GH synthesis. Therefore, ghrelin is believed to play a role in promoting bone growth and development. The correlation between ghrelin and some degenerative diseases of the musculoskeletal system has been reported recently, and ghrelin may be one of the factors influencing degenerative pathologies, such as osteoporosis, osteoarthritis, sarcopenia and intervertebral disc degeneration. With population ageing, the risk of health problems caused by degenerative diseases of the musculoskeletal system gradually increases. In this article, the roles of ghrelin in musculoskeletal disorders are summarized to reveal the potential effects of ghrelin as a key target in the treatment of related bone and muscle diseases and the need for further research.

Association of Short-Chain Fatty Acids with Gut Microbiota and Lipid Metabolism in Mice with Diarrhea Induced by High-Fat Diet in a Fatigued State.

Preliminary research finds that a high-fat diet (HFD) in a fatigued state triggers diarrhea, but the exact mechanism has not been clarified. To address concerns about the pathogenesis of diarrhea, the study evaluates the composition and metabolomics of the gut microbiota. The study uses the multiple platform apparatus device to induce fatigue in mice, combined with intragastric administration of lard-caused diarrhea. Subsequently, the characteristics and interaction relationship of gut microbiota, short-chain fatty acids (SCFAs), inflammatory biomarkers, brain-gut peptides, and lipid metabolism are analyzed at the end of the experiment. HFD in a fatigued state results in a significant increase in interleukin-17, interleukin-6, cholecystokinin, somatostatin, and malondialdehyde content in mice (p < 0.05), along with a substantial decrease in high-density lipoprotein (p < 0.05). Additionally, an HFD in a fatigued state causes changes in the structure and composition of the gut microbiota, with Lactobacillus murinus as its characteristic bacteria, and reduces the production of SCFAs. An HFD in a fatigued state triggers diarrhea, possibly associated with gut content microbiota dysbiosis, SCFAs deprivation, increased inflammation, and dysregulated lipid metabolism.

The Mechanism of the Gut-Brain Axis in Regulating Food Intake.

With the increasing prevalence of energy metabolism disorders such as diabetes, cardiovascular disease, obesity, and anorexia, the regulation of feeding has become the focus of global attention. The gastrointestinal tract is not only the site of food digestion and absorption but also contains a variety of appetite-regulating signals such as gut-brain peptides, short-chain fatty acids (SCFAs), bile acids (BAs), bacterial proteins, and cellular components produced by gut microbes. While the central nervous system (CNS), as the core of appetite regulation, can receive and integrate these appetite signals and send instructions to downstream effector organs to promote or inhibit the body's feeding behaviour. This review will focus on the gut-brain axis mechanism of feeding behaviour, discussing how the peripheral appetite signal is sensed by the CNS via the gut-brain axis and the role of the central "first order neural nuclei" in the process of appetite regulation. Here, elucidation of the gut-brain axis mechanism of feeding regulation may provide new strategies for future production practises and the treatment of diseases such as anorexia and obesity.

Exercise for Mental Well-Being: Exploring Neurobiological Advances and Intervention Effects in Depression.

Depression is a common mental disorder in which patients often experience feelings of sadness, fatigue, loss of interest, and pleasure. Exercise is a widely used intervention for managing depression, but the specific molecular mechanisms underlying its antidepressant effect are unclear. In this narrative review, we aim to synthesize current knowledge on the molecular, neural, and physiological mechanisms through which exercise exerts its antidepressant effect and discuss the various exercise interventions used for managing depression. We conducted a narrative review of the literature on the topic of exercise and depression. Our review suggests that exercise impacts peripheral tryptophan metabolism, central inflammation, and brain-derived neurotrophic factors through the peroxisome proliferator-activated receptor γ activating factor 1α (PGC-1α) in skeletal muscles. The uncarboxylated osteocalcin facilitates "bone-brain crosstalk", and exercise corrects atypical expression of brain-gut peptides, modulates cytokine production and neurotransmitter release, and regulates inflammatory pathways and microRNA expression. Aerobic exercise is recommended at frequencies of 3 to 5 times per week with medium to high intensity. Here we highlight the significant potential of exercise therapy in managing depression, supported by the molecular, neural, and physiological mechanisms underlying its antidepressant effect. Understanding the molecular pathways and neural mechanisms involved in exercise's antidepressant effect opens new avenues for developing novel therapies for managing depression.