The antidepressant effect of Komagataella pastoris KM 71 H in maternal separation mice model mediated by the microbiota-gut-brain axis.

BACKGROUND: The intestinal microbiota plays a fundamental role in maintaining host health, especially during childhood, a critical period for its establishment. Early life stress can lead to shifts in gut microbiota composition, thus increasing the risk of major depressive disorder (MDD) in adulthood. The supplementation with probiotics restores intestinal permeability and the health of gut microbial communities, therefore being potential study targets for the treatment of MDD. In this sense, the yeast Komagataella pastoris was reported as a promising probiotic with antidepressant effect. METHODS: Hence, the present study aims to investigate this effect in mice submitted to maternal separation (MS) 3 h per day from PND2 to PND14. Adult mice and mothers were treated with K. pastoris KM71H (8 log UFC.g-1/per animal, i.g.) or PBS (500 µl, i.g.) for 14 days. After behavioral tests, the animals were euthanized, followed by hippocampi and intestines removal for biochemical analysis. RESULTS: On behavioral tests, K. pastoris KM71H treatment reduced the immobility time in TST of adult mice and increased the grooming activity in splash test of adult mice and mothers induced by MS. The probiotic treatment restored plasma corticosterone levels and glucocorticoid receptor expression in hippocampi, alongside nitrate/nitrite levels and superoxide dismutase activity in intestine, in addition to reducing reactive species levels in both structures. Moreover, it also normalized the fecal pH and water content of feces. CONCLUSION: Thus, we conclude that K. pastoris KM71H is a promising therapeutic strategy for the treatment of MDD.

Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.

More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.

Gut microbiome and Alzheimer's disease: what we know and what remains to be explored.

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.

Association Between Stress, Neuroinflammation, and Irritable Bowel Syndrome: The Positive Effects of Probiotic Therapy.

Stress refers to an organism's response to environmental threats in normal condition to maintain homeostasis in the body. In addition, strong inflammatory reactions induced by the hypothalamic-pituitary-adrenal (HPA) axis under stress condition during a long time. Reciprocally, chronic stress can induce the irritable bowel syndrome (IBS) which is a well-known gut disorder thereby play an important role in the promotion and pathophysiology of neuropsychiatric diseases. It has been demonstrated that leaky gut is a hallmark of IBS, leads to the entrance the microbiota into the bloodstream and consequent low-grade systemic inflammation. In the current review, we will discuss the mechanisms by which stress can influence the risk and severity of IBS and its relationship with neuroinflammation. Also, the role of probiotics in IBS co-existing with chronic stress conditions is highlighted.

Probiotics as a targeted intervention in anti-aging: A review.

The age-induced disruption of gut flora, termed gut dysbiosis, is intimately tied to compromised immune function, augmented oxidative stress, and a spectrum of age-linked disorders. This review examines the fundamental mechanisms employed by probiotic strains to modulate gut microbiota composition and metabolic profiles, mitigate cognitive decline via the gut-brain axis, modulate gene transcription, and alleviate inflammatory responses and oxidative stress. We elucidate the capacity of probiotics as a precision intervention to restore gut microbiome homeostasis and alleviate age-related conditions, thereby offering a theoretical framework for probiotics to decelerate aging, manage age-related diseases, and elevate quality of life.

Transfer of microbiota from lean donors in combination with prebiotics prevents excessive weight gain and improves gut-brain vagal signaling in obese rats.

Gastrointestinal (GI) microbiota plays an active role in regulating the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and studies have shown that high fat (HF) diets induce detrimental changes (dysbiosis) in the GI bacterial makeup. HF diet induced dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if improving microbiota composition after diet-induced obesity has been established can ameliorate gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male rats were maintained on regular chow or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using antibiotics. The animals were then divided into four groups (n = 10 each): LF - control fed regular chow, LF-LF - chow fed animals that received microbiota from chow fed donors, HF-LF - HF fed animals that received microbiota from chow fed donors, and HF-HF - HF fed animals that received microbiota from HF fed donors. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome. We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons. We concluded from these data that improving microbiota composition in obese rats is sufficient to ameliorate gut-brain communication and restore normal feeding patterns which was associated with a reduction in weight gain.

A pathophysiologic framework for the overlap of disorders of gut-brain interaction and the role of the gut microbiome.

The International Rome Committee defines Disorders of Gut-Brain Interactions (DGBI) based upon distinct combinations of chronic and/or recurrent unexplained gastrointestinal symptoms. Yet patients often experience overlapping DGBI. Patients with DGBI frequently also suffer from extraintestinal symptoms, including fatigue, sleep disturbances, anxiety, and depression. Patients with overlapping DGBI typically experience more severe GI symptoms and increased psychosocial burden. Concerning the pathophysiology, DGBI are associated with disruptions in gut motility, function of the brain and enteric neurons, immune function, and genetic markers, with recent findings revealing gut microbiome alterations linked to these mechanisms of DGBI. Emerging evidence summarized in this review suggests that the microbiome influences various established disease mechanisms of different DGBI groups. Overall, changes in the gastrointestinal microbiome do not seem to be linked to a specific DGBI subgroup but may play a key role in the manifestation of different DGBI and, subsequently, overlap of DGBI. Understanding these shared mechanisms and the role of the gastrointestinal microbiome, particularly for overlapping DGBI, might aid in developing more precise diagnostic criteria and treatment strategies while developing personalized interventions that target specific mechanisms to improve patient outcomes.

Gut microbiota and irritable bowel syndrome: status and prospect.

Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients' quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.

Asiaticoside improves depressive-like behavior in mice with chronic unpredictable mild stress through modulation of the gut microbiota.

Background: Asiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression. Methods: Behavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA. Results: This study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic-pituitary-adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis. Conclusions: These results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model.

Oxyntomodulin physiology and its therapeutic development in obesity and associated complications.

Incretins, such as glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), have advanced the treatment landscape of obesity to a new pinnacle. As opposed to singular incretin effects, oxyntomodulin (OXM) activates glucagon receptors (GCGR) and glucagon-like peptide-1 receptors (GLP1R), demonstrating a more dynamic range of effects that are more likely to align with evolving 'health gains' goals in obesity care. Here, we will review the molecular insights from their inception to recent developments and challenges. This review will discuss the physiological actions of OXM, primarily appetite regulation, energy expenditure, and glucose homeostasis. Finally, we will shed light on the development of OXM-based therapies for obesity and associated complications, and outline important considerations for more translational efforts.

From gut to brain: unveiling probiotic effects through a neuroimaging perspective-A systematic review of randomized controlled trials.

The gut-brain axis, a bidirectional communication network between the gastrointestinal system and the brain, significantly influences mental health and behavior. Probiotics, live microorganisms conferring health benefits, have garnered attention for their potential to modulate this axis. However, their effects on brain function through gut microbiota modulation remain controversial. This systematic review examines the effects of probiotics on brain activity and functioning, focusing on randomized controlled trials using both resting-state and task-based functional magnetic resonance imaging (fMRI) methodologies. Studies investigating probiotic effects on brain activity in healthy individuals and clinical populations (i.e., major depressive disorder and irritable bowel syndrome) were identified. In healthy individuals, task-based fMRI studies indicated that probiotics modulate brain activity related to emotional regulation and cognitive processing, particularly in high-order areas such as the amygdala, precuneus, and orbitofrontal cortex. Resting-state fMRI studies revealed changes in connectivity patterns, such as increased activation in the Salience Network and reduced activity in the Default Mode Network. In clinical populations, task-based fMRI studies showed that probiotics could normalize brain function in patients with major depressive disorder and irritable bowel syndrome. Resting-state fMRI studies further suggested improved connectivity in mood-regulating networks, specifically in the subcallosal cortex, amygdala and hippocampus. Despite promising findings, methodological variability and limited sample sizes emphasize the need for rigorous, longitudinal research to clarify the beneficial effects of probiotics on the gut-brain axis and mental health.

A New Plant Active Polysaccharide from Nicotiana Improves the Lead-Led Impairment of Spatial Memory in Mice by Modulating the Gut Microbiota and IL-6.

Active polysaccharides from plants are broadly applied in the food and health industry. The purpose of this study is to identify a new plant active polysaccharide and to investigate its role in modulating spatial memory. Ultrasonics and DEAE-52 chromatography were used to separate and purify the plant active polysaccharide (PAP). Mice were exposed to 100 ppm of lead acetate from birth to 7 weeks old to establish the memory impairment model. PAPs with concentrations of 200 or 400 ppm were fed to the subject mice each day after weaning in a spatiotemporally separated fashion. At the end of the intervention, mice were examined using the Morris water maze test, microbiome sequencing, cytokine profiling and protein analysis. The derived active polysaccharide was constituted by ß-anomeric carbon, indicating a new form of PAP. The PAP significantly ameliorates the memory impairment caused by postnatal lead exposure, as evidenced by the preferred coverage of the test mouse in the hidden platform, demonstrating salient neuroregulatory activity. In terms of the gut microbiome in response to PAP treatment, it was found that the 400 ppm PAP reversed the gut dysbiosis, producing a comparable structure to the intact animals, represented by the relative abundance of Firmicutes and Muribaculum, Desulfovibrio, etc. For cytokines, the PAP reversed the plasma levels of IL-6, suggesting an anti-inflammatory trend in the context of proinflammation caused by lead invasion. By injecting an IL-6 antagonist, Tocilizumab, into the deficient mice, the spatial memory was significantly repaired, which demonstrates the central roles of IL-6 in mediating the positive effect of the PAP. Finally, a histone modification mark, H3K27me3, was found to be potent in responding to the signals conveyed by the PAP. The PAP could improve the memory deficits by remodeling the gut-brain axis centered at the microbiota and IL-6, which is regarded as an important cytokine-modulating brain activity. This is an intriguing instance linking neuromodulation with the active polysaccharide, shedding light on the innovative applications of plant polysaccharides due to the scarcity of similar phenotypic connections.

The gut-brain axis in appetite, satiety, food intake, and eating behavior: Insights from animal models and human studies.

The gut-brain axis plays a pivotal role in the finely tuned orchestration of food intake, where both homeostatic and hedonic processes collaboratively control our dietary decisions. This interplay involves the transmission of mechanical and chemical signals from the gastrointestinal tract to the appetite centers in the brain, conveying information on meal arrival, quantity, and chemical composition. These signals are processed in the brain eventually leading to the sensation of satiety and the termination of a meal. However, the regulation of food intake and appetite extends beyond the realms of pure physiological need. Hedonic mechanisms, including sensory perception (i.e., through sight, smell, and taste), habitual behaviors, and psychological factors, exert profound influences on food intake. Drawing from studies in animal models and human research, this comprehensive review summarizes the physiological mechanisms that underlie the gut-brain axis and its interplay with the reward network in the regulation of appetite and satiety. The recent advancements in neuroimaging techniques, with a focus on human studies that enable investigation of the neural mechanisms underpinning appetite regulation are discussed. Furthermore, this review explores therapeutic/pharmacological strategies that hold the potential for controlling food intake.

Oral Trehalose Intake Modulates the Microbiota-Gut-Brain Axis and Is Neuroprotective in a Synucleinopathy Mouse Model.

Parkinson's disease (PD) is a neurodegenerative disease affecting dopaminergic neurons in the nigrostriatal and gastrointestinal tracts, causing both motor and non-motor symptoms. This study examined the neuroprotective effects of trehalose. This sugar is confined in the gut due to the absence of transporters, so we hypothesized that trehalose might exert neuroprotective effects on PD through its action on the gut microbiota. We used a transgenic mouse model of PD (PrP-A53T G2-3) overexpressing human α-synuclein and developing GI dysfunctions. Mice were given water with trehalose, maltose, or sucrose (2% w/v) for 6.5 m. Trehalose administration prevented a reduction in tyrosine hydroxylase immunoreactivity in the substantia nigra (-25%), striatum (-38%), and gut (-18%) in PrP-A53T mice. It also modulated the gut microbiota, reducing the loss of diversity seen in PrP-A53T mice and promoting bacteria negatively correlated with PD in patients. Additionally, trehalose treatment increased the intestinal secretion of glucagon-like peptide 1 (GLP-1) by 29%. Maltose and sucrose, which break down into glucose, did not show neuroprotective effects, suggesting glucose is not involved in trehalose-mediated neuroprotection. Since trehalose is unlikely to cross the intestinal barrier at the given dose, the results suggest its effects are mediated indirectly through the gut microbiota and GLP-1.

Impact of Lyophilized Milk Kefir-Based Self-Nanoemulsifying System on Cognitive Enhancement via the Microbiota-Gut-Brain Axis.

Chronic inflammatory bowel disorders (IBDs) are characterized by altered intestinal permeability, prompting inflammatory, oxidative stress, and immunological factors. Gut microbiota disorders impact brain function via the bidirectional gut-brain axis, influencing behavior through inflammatory cascades, oxidative stress, and neurotransmitter levels. This study highlights the potential effect of integrating lyophilized milk kefir alone and lyophilized milk kefir as solid carriers loaded with a self-nanoemulsifying self-nanosuspension (SNESNS) of licorice extract on an induced chronic IBD-like model in rats. Licorice-SNESNS was prepared by the homogenization of 30 mg of licorice extract in 1 g of the selected SNEDDS (30% Caraway oil, 60% Tween 20, and 10% propylene glycol (w/w)). Licorice-SNESNS was mixed with milk kefir and then freeze-dried. Dynamic TEM images and the bimodal particle size curve confirmed the formation of the biphasic nanosystems after dilution (nanoemulsion and nanosuspension). Daily oral administration of lyophilized milk kefir (100 mg/kg) loaded with SNESNS (10 mg/kg Caraway oil and 1 mg/kg licorice) restored normal body weight and intestinal mucosa while significantly reducing submucosal inflammatory cell infiltration in induced rats. Importantly, this treatment demonstrated superior efficacy compared to lyophilized milk kefir alone by leading to a more significant alleviation of neurotransmitter levels and improved memory functions, thereby addressing gut-brain axis disorders. Additionally, it normalized fecal microbiome constituents, inflammatory cytokine levels, and oxidative stress in examined tissues and serum. Moreover, daily administration of kefir-loaded SNESNS normalized the disease activity index, alleviated histopathological changes induced by IBD induction, and partially restored the normal gut microbiota. These alterations are associated with improved cognitive functions, attributed to the maintenance of normal neurotransmitter levels and the alleviation of triggered inflammatory factors and oxidative stress levels.

Ex vivo and miniaturized in vitro models to study microbiota-gut-brain axis.

The microbiota-gut-brain axis involves complex bidirectional communication through neural, immune, and endocrine pathways. Microbial metabolites, such as short-chain fatty acids, influence gut motility and brain function by interacting with gut receptors and modulating hormone release. Additionally, microbial components such as lipopolysaccharides and cytokines can cross the gut epithelium and the blood-brain barrier, impacting immune responses and cognitive function. Ex vivo models, which preserve gut tissue and neural segments, offer insight into localized gut-brain communication by allowing for detailed study of nerve excitability in response to microbial signals, but they are limited in systemic complexity. Miniaturized in vitro models, including organ-on-chip platforms, enable precise control of the cellular environment and simulate complex microbiota-host interactions. These systems allow for the study of microbial metabolites, immune responses, and neuronal activity, providing valuable insights into gut-brain communication. Despite challenges such as replicating long-term biological processes and integrating immune and hormonal systems, advancements in bioengineered platforms are enhancing the physiological relevance of these models, offering new opportunities for understanding the mechanisms of the microbiota-gut-brain axis. This review aims to describe the ex vivo and miniaturized in vitro models which are used to mimic the in vivo conditions and facilitate more precise studies of gut brain communication.

The Gut-Brain Axis and Neuroinflammation in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major global disability and mortality cause, with the gut-brain axis playing a crucial role in its pathophysiology. Neuroinflammation, triggered by microglia and astrocytes, contributes to neuronal damage and cognitive impairment. This paper aims to explore the relationship between the gut-brain axis and neuroinflammation in TBI and its potential implications for therapeutic interventions. A comprehensive review of the literature was conducted using PubMed, MEDLINE, and Google Scholar databases. Studies investigating the gut-brain axis, neuroinflammation, and TBI were included. Evidence suggests that TBI disrupts the gut-brain axis, leading to alterations in gut microbiota composition, intestinal permeability, and immune responses. These gut-related changes promote the activation of microglia and astrocytes in the central nervous system, contributing to neuroinflammation and neuronal damage. Conversely, interventions that modulate gut microbiota or reduce intestinal permeability have been shown to attenuate neuroinflammation and improve cognitive outcomes in TBI models. The gut-brain axis plays a significant role in the pathogenesis of neuroinflammation following TBI. Targeting the gut-brain axis through interventions that restore gut homeostasis and reduce intestinal permeability holds promise as a novel therapeutic strategy for mitigating neuroinflammation and improving cognitive function in TBI patients. Further research is needed to elucidate the specific mechanisms involved and to develop effective therapies based on this understanding.

Multi-omics insights into the microbiota-gut-brain axis and cognitive improvement post-bariatric surgery.

BACKGROUND: Although numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA). METHODS: Demographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors. RESULTS: LSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05). CONCLUSION: These findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/ .

Ghrelin in Depression: A Promising Therapeutic Target.

Depression is a widespread disease affecting over 300 million individuals of various ethnicities and socioeconomic backgrounds globally. It frequently strikes early in life and becomes a chronic or recurring lifelong illness. Out of the various hypotheses for the pathophysiology of depression, the gut-brain axis and stress hypothesis are the ones that need to be researched, as psychological stress impairs one or more pathways of the brain-gut axis and is likely to cause brain-gut axis dysfunction and depression. A dysfunctional reciprocal gut-brain relationship may contribute to many diseases, including inflammatory disorders, abnormal stress responses, impaired behavior, and metabolic changes. The hormone ghrelin is a topic of interest concerning the gut-brain axis as it interacts with the gut-brain axis indirectly via the central nervous system or via crossing the blood-brain barrier. Ghrelin release is also affected by the gut microbes, which has also been discussed in the review. This review elaborates on Ghrelin's role in depression and its effect on various aspects like neurogenesis, HPA axis, and neuroinflammation. Furthermore, this review focuses on ghrelin as a potential target for alleviation of depressive symptoms.

The emerging role of gut hormones.

The gut is traditionally recognized as the central organ for the digestion and absorption of nutrients, however it also functions as a significant endocrine organ, secreting a variety of hormones such as glucagon-like peptide 1 (GLP-1), serotonin, somatostatin, and glucocorticoids. These gut hormones, produced by specialized intestinal epithelial cells (IECs), are crucial not only for digestive processes but also for the regulation of a wide range of physiological functions, including appetite, metabolism, and immune responses. While gut hormones can exert systemic effects, they also play a pivotal role in maintaining local homeostasis within the gut. This review discusses the role of the gut as an endocrine organ, emphasizing the stimuli, the newly discovered functions, and the clinical significance of gut-secreted hormones. Deciphering the emerging role of gut hormones will lead to a better understanding of gut homeostasis, innovative treatments for disorders in the gut as well as systemic diseases.