The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

JOURNAL/nrgr/04.03/01300535-202508000-00002/figure1/v/2024-09-30T120553Z/r/image-tiff Traumatic brain injury is a prevalent disorder of the central nervous system. In addition to primary brain parenchymal damage, the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury; however, the underlying pathogenesis remains unclear, and effective intervention methods are lacking. Intestinal dysfunction is a significant consequence of traumatic brain injury. Being the most densely innervated peripheral tissue in the body, the gut possesses multiple pathways for the establishment of a bidirectional "brain-gut axis" with the central nervous system. The gut harbors a vast microbial community, and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal, hormonal, and immune pathways. A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications. We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury, with a specific focus on the complex biological processes of peripheral nerves, immunity, and microbes triggered by traumatic brain injury, encompassing autonomic dysfunction, neuroendocrine disturbances, peripheral immunosuppression, increased intestinal barrier permeability, compromised responses of sensory nerves to microorganisms, and potential effector nuclei in the central nervous system influenced by gut microbiota. Additionally, we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury. This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the "brain-gut-microbiota axis."

Acute stress can enhance or impair synaptic plasticity depending on the nature, duration, and type of stress exposure as well as the brain region examined. The absence of a gut microbiome can also alter hippocampal plasticity. However, the possible interplay between synaptic plasticity, acute stress, and the gut microbiota remains unknown. Here, we examine this interaction and determine whether the gut microbiota impacts stress-induced alterations in hippocampal plasticity. Further, we explored whether exposure to the microbial metabolite butyrate is sufficient to counteract stress-induced alterations in synaptic plasticity. We used electrophysiological and molecular experiments in adult male C57/BL6 antibiotic-treated and acutely stressed mice. In electrophysiological experiments we treated hippocampal slices with 3 μM sodium butyrate to explore the effect of this microbial metabolite. We found the presence of the microbiota essential for the enhancement of both short- and long-term potentiation induced by 15 min of acute restraint stress. Furthermore, butyrate exposure effectively restored the stress-induced enhancement of potentiation in slices from microbiome-depleted animals while also enhancing long-term potentiation independent of stress. In addition, alterations of hippocampal synaptic plasticity markers were noted. Our findings highlight a critical new temporal role for gut-derived metabolites in defining the impact of acute stress on synaptic plasticity.

Obstructive sleep apnea (OSA) and depression are highly comorbid. Increased intestinal permeability has been hypothesized to play a role in the pathogenesis of both. The current study aimed to assess the severity of OSA symptoms, comorbid depressive symptoms, and lipopolysaccharide-binding protein (LBP) levels in adult patients being diagnosed for OSA syndrome. The study population consisted of 176 subjects. An apnea-hypopnea index (AHI) ≥ 5/hour was used for the diagnosis of OSA syndrome. Depressive symptoms were assessed with the Beck Depression Inventory-2. LBP levels were measured in the blood serum by enzyme-linked immunosorbent assay (ELISA). Associations between clinical symptom profiles or severity and LBP as an intestinal permeability biomarker marker were tested. LBP levels were not different between patients with different OSA severity, as assessed with AHI or daily sleepiness. Nor were LBP levels different in subjects with different depressiveness severity. Daily sleepiness was weakly positively correlated with depression score, and LBP levels correlated positively with a neutrophils-to-lymphocytes ratio. Finally, LBP levels were not explained by multiple linear regression models, including sleep-related parameter values and depression score. Intestinal permeability, as measured with LBP level, may not explain the comorbidity of depression and daily sleepiness in the course of OSA syndrome.

According to the criteria established by the International League Against Epilepsy (ILAE), epilepsy is defined as a disorder characterized by at least two unprovoked seizures occurring more than 24 h apart. Its pathogenesis is closely related to various physiological and pathological factors. Advances in high-throughput metagenomic sequencing have increasingly highlighted the role of gut microbiota dysbiosis in epilepsy. Short-chain fatty acids (SCFAs), the major metabolites of the gut microbiota and key regulators of the gut-brain axis, support physiological homeostasis through multiple mechanisms. Recent studies have indicated that SCFAs not only regulate seizures by maintaining intestinal barrier integrity and modulating intestinal immune responses, but also affect the structure and function of the blood-brain barrier (BBB) and regulate neuroinflammation. This review, based on current literatures, explores the relationship between SCFAs and epilepsy, emphasizing how SCFAs affect epilepsy by modulating the intestinal barrier and BBB. In-depth studies on SCFAs may reveal their therapeutic potential and inform the development of gut microbiota-targeted epilepsy treatments.

Nitric oxide is a vasodilator molecule that acts on blood pressure (BP) control, and its production can occur through the reduction of nitrates by oral or intestinal nitrate-reducing bacteria. However, the relationship between nitrate-reducing bacteria and arterial hypertension (HTN) remains under debate.

Systematically review if there is an association between the abundance of oral and intestinal nitrate-reducing bacteria and the occurrence of HTN in humans.

MEDLINE, Scopus, Cochrane Library, EMBASE, LILACS, Web of Science, Livivo, ProQuest Dissertations, and Google Scholar were searched for eligible articles until February 10th, 2024. Studies were included if they: (1) were observational studies or clinical trials; (2) included adults (≥18 years old) with HTN (systolic BP ≥ 130 mmHg and/or diastolic BP > 80 mmHg and/or use of BP lowering medication); (3) compared (or not) to no-HTN adults; and (4) used next-generation sequencing microbiome analysis to identify bacterial taxa in the oral and/or gut nitrate-reducing bacteria.

The search identified 9365 articles, and 28 were included in the study after applying the inclusion and exclusion criteria; 23 articles assessed the gut microbiota, 4 assessed the oral microbiota, and 1 assessed both. Depletion of nitrate-reducing bacteria was not consistently shown in the studies. The included studies reported reduction, increase, and no change in the nitrate-reducing bacteria genera or species in oral or gut microbiota.

We found no association between the abundance of oral and gut nitrate-reducing bacteria and the occurrence of HTN in humans.

PROSPERO identification number CRD42022315891.

The gut microbiome has emerged as a novel and intriguing focus in mood disorder research. Emerging evidence demonstrates the significant role of the gut microbiome in influencing mental health, suggesting a bidirectional communication between the gut and the brain. This review examines the latest findings on the gut-microbiota-brain axis and elucidates how alterations in gut microbiota composition can influence this axis, leading to changes in brain function and behavior. Although dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation have yielded encouraging results, significant advances are needed to establish next-generation approaches that precisely target the neurobiological mechanisms of mood disorders. Future research must focus on developing personalized treatments, facilitated by innovative therapies and technological progress, which account for individual variables such as age, sex, drug history, and lifestyle. Highlighting the potential therapeutic implications of targeting the gut microbiota, this review emphasizes the importance of integrating microbiota research into psychiatric studies to develop more effective and personalized treatment strategies for mood disorders.

The therapeutic targeting of the intestinal microbiota has gained increasing attention as a promising avenue for addressing mood disorders. This study aimed to assess the potential effect of supplementing standard pharmacological treatment with the probiotic kefir in patients with Major Depressive Disorder (MDD).

Thirty-eight female participants diagnosed with moderate MDD by the Hamilton Rating Scale for Depression (HAM-D) were selected to receive the probiotic kefir in conjunction with antidepressant therapy for 12 weeks. The participants were evaluated at baseline (T0) and 90 days after probiotic kefir supplementation (T90). HAM-D scores and blood samples were collected at both time points.

Probiotic supplementation significantly reduced MDD severity, as evidenced by lower HAM-D scores compared to baseline. Probiotic consumption for 90 days also significantly decreased interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels compared to baseline. However, probiotic kefir supplementation did not significantly affect serum serotonin levels. Additionally, after 90 days of probiotic consumption, insulin and morning cortisol levels were significantly reduced. In contrast, no significant changes were observed in serum levels of prolactin, vitamin D, and afternoon cortisol.

This study provides valuable insights into the potential benefits of probiotics, specifically kefir, as adjunctive therapy for female patients with MDD. The findings highlight promising results in ameliorating depressive symptoms and modulating inflammatory and hormonal markers.

High fluoride exposure was widely demonstrated to be related with brain memory impairment. Since the absorption of F- enters the body mainly through the gastrointestinal tract, studying the effects of excessive intake of fluoride on brain memory function in various gut microbiome states might have profound implications for the prevention of fluorosis because growing evidence revealed the significance of the "microbiota-gut-brain" axis (MGBA). In the present study, we aimed to illustrate the potential mechanism of gut microbiota on high fluoride exposure-induced hippocampal lesions and spatial memory dysfunction in mice by the various intestinal microecological environments, which were constructed by antibiotic treatment. Mice fed with normal (CG1 and Exp1 groups) or sodium-fluoride (CG2 and Exp2 groups; 24 mg/kg sodium fluoride per mouse) by gavage administration with or without antibiotic treatments, a combination of metronidazole (1 g/L) and ciprofloxacin (0.2 g/L) in drinking water. Mice gavaged with excessive sodium fluoride alone exhibited reduced weight gain, hippocampal tissue damages, spatial memory levels dysfunction, impaired intestinal permeability, decreased inflammatory cytokines expression and antioxidant capability in the hippocampal and ileal tissues. In contrast, antibiotic intervention significantly reversed these high fluoride exposure-induced hippocampal and ileal changes.16S rRNA high throughput sequencing found that ileal microbiota were dominated by abundant taxa, which is conducive to constructing microbial interaction networks and module communities, and identifying keystone species targeted by high fluoride exposure compared with colonic microbiome. In addition, the microbial community composition and assembly mechanism of ileal microbiome under the effects of antibiotics were suitable for revealing the characteristics of high fluoride environment. In the later analysis, Lactobacillus, Staphylococcus, Muribaculaceae and Robinsoniella were considered as the keystone species targeted by high fluoride-exposed mice based on the analysis of network node properties and niche overlap of ileal microbes. Spearman rank correlation demonstrated that these keystone species had significant effects on hippocampal memory levels and intestinal health, as well as microbial communities functions. Compared to previous researches, this study further revealed intestinal microbial coummunity mediated the underlying mechanism through antibiotic treatment against high fluoride-induce hippocampal spatial memory impairment.

We explored the mechanisms underlying the improvement of postoperative ileus (POI) following probiotic pretreatment. We assessed intestinal permeability, inflammation, tight junction (TJ) protein expression in the gut epithelium, and plasma interleukin (IL)-17 levels in a guinea pig model of POI.

Guinea pigs were divided into control, POI, and probiotic groups. The POI and probiotic groups underwent surgery, but the probiotic group received probiotics before the procedure. The ileum and proximal colon were harvested. Intestinal permeability was measured via horseradish peroxidase permeability. Inflammation was evaluated via leukocyte count in the intestinal wall muscle layer, and calprotectin expression in each intestinal wall layer was analyzed immunohistochemically. TJ proteins were analyzed using immunohistochemical staining, and plasma IL-17 levels were measured using an enzyme-linked immunosorbent assay.

The POI group exhibited increased intestinal permeability and inflammation, whereas probiotic pretreatment reduced the extent of these POI-induced changes. Probiotics restored the expression of TJ proteins occludin and zonula occludens-1 in the proximal colon, which were increased in the POI group. Calprotectin expression significantly increased in the muscle layer of the POI group and was downregulated in the probiotic group; however, no distinct differences were observed between the mucosal and submucosal layers. Plasma IL-17 levels did not significantly differ among the groups.

Probiotic pretreatment may relieve POI by reducing intestinal permeability and inflammation and TJ protein expression in the gut epithelium. These findings suggest a potential therapeutic approach for POI management.

Background: Emerging evidence suggests that the maternal microbiome plays a crucial role in shaping fetal neurodevelopment, immune programming, and metabolic health. Dysbiosis during pregnancy-whether gastrointestinal, oral, or vaginal-can significantly influence pregnancy outcomes and long-term child health. Materials and Methods: The search was performed using databases such as PubMed, Scopus, and Google Scholar including research published from January 2000 to January 2025. The keywords used were "Fetal Programming", " Maternal Immune Activation", "Maternal microbiome", "Microbiota-Gut-Brain Axis", and "Pregnancy Dysbiosis". Results: The maternal microbiome undergoes substantial changes during pregnancy, with alterations in microbial diversity and function linked to conditions such as gestational diabetes, obesity, and preeclampsia. Pregnancy-related dysbiosis has been associated with adverse neurodevelopmental outcomes, including an increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and cognitive impairments in offspring. Conclusions: Understanding the intricate relationship between maternal microbiota and fetal health is essential for developing targeted interventions. Personalized microbiome-based strategies, including dietary modifications and probiotic supplementation, hold promise in optimizing pregnancy outcomes and promoting health in offspring.

A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.

Sexual dysfunction, influenced by hormonal imbalances, psychological factors, and chronic diseases, affects a significant portion of the population. Probiotics, known for their beneficial effects on gut microbiota, have emerged as potential therapeutic agents for improving sexual health. This systematic review evaluates the impact of probiotics on sexual function, hormonal regulation, and reproductive outcomes. A comprehensive search identified 3308 studies, with 12 meeting the inclusion criteria-comprising 10 randomized controlled trials (RCTs) and 2 in vivo and in vitro studies. Probiotic interventions were shown to significantly improve sexual function, particularly in women undergoing antidepressant therapy (p < 0.05). Significant improvements in Female Sexual Function Index (FSFI) scores were observed, with combined treatments such as Lactofem with Letrozole and Lactofem with selective serotonin reuptake inhibitors (SSRIs) demonstrating a 10% biochemical and clinical pregnancy rate compared to 0% in the control group (p = 0.05). Probiotic use was also associated with a 66% reduction in menopausal symptoms, increased sperm motility (36.08%), viability (46.79%), and morphology (36.47%). Probiotics also contributed to favorable hormonal changes, including a reduced luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio (from 3.0 to 2.5, p < 0.05) and increased testosterone levels. Regarding reproductive outcomes, probiotic use was associated with higher pregnancy rates in women undergoing fertility treatments and improvements in sperm motility, viability, and morphology in men. This review highlights the promising role of probiotics in addressing sexual dysfunction and reproductive health, suggesting their potential as adjunctive treatments for conditions such as depression and infertility. Further research is needed to better understand the underlying mechanisms of these beneficial effects.

Depression is a mental disorder, and genistein is known to have antidepressant effects, but its mechanism of action is still unclear. Here, the mechanism of genistein improving depression based on gut microbiota was explored using classic behavioral indicators of depression combined with genomic technology. The behavioral evaluation showed that rats gavaged with 20-40 mg/kg genistein showed an increase in body weight, glucose preference, absenteeism score, body temperature, and 5-hydroxytryptamine (5-HT) content, while a decrease in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) content compared to the depression rat model group, but there was no significant difference compared to the positive control (fluoxetine). The results of high-throughput sequencing showed that genistein increased the relative abundance of Firmicutes and Actinobacteriota and decreased the relative abundance of Bacteroidota at the phylum level. At the genus level, the abundance of Bifidobacterium, a short-chain fatty acid producing bacterium, was increased. Furthermore, metagenome results revealed that the antidepressant effect of genistein can be achieved by promoting glutamate metabolism, increasing glutamic acid decarboxylase (GAD) expression levels, promoting γ-aminobutyric acid (GABA) synthesis, and indirectly increasing 5-HT levels.

Although depression is a leading cause of disability worldwide, the pathophysiological mechanisms underlying this disorder-particularly those involving the gut microbiome-are poorly understood.

To investigate, we conducted a community-based observational study to explore complex associations between changes in the gut microbiome, cytokine levels, and depression symptoms in 51 participants (Mage = 49.56, SD = 13.31) receiving an immersive psychosocial intervention. A total of 142 multi-omics samples were collected from participants before, during, and three months after the nine-day inquiry-based stress reduction program.

Results revealed that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1.

These findings reveal a potentially protective link between the Prevotella-dominant microbiome and depression, as evidenced by a reduced pro-inflammatory environment and fewer depressive symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, may highlight potential avenues for microbiome-targeted therapies for managing depression.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

This review explores the intricate relationships among the gut microbiota, dietary patterns, and mental health, focusing specifically on depression. It synthesizes insights from microbiological, nutritional, and neuroscientific perspectives to understand how the gut-brain axis influences mood and cognitive function.

Recent studies underscore the central role of gut microbiota in modulating neurological and psychological health via the gut-brain axis. Key findings highlight the importance of dietary components, including probiotics, prebiotics, and psychobiotics, in restoring microbial balance and enhancing mood regulation. Different dietary patterns exhibit a profound impact on gut microbiota composition, suggesting their potential as complementary strategies for mental health support. Furthermore, mechanisms like tryptophan metabolism, the HPA axis, and microbial metabolites such as SCFAs are implicated in linking diet and microbiota to depression. Clinical trials show promising effects of probiotics in alleviating depressive symptoms. This review illuminates the potential of diet-based interventions targeting the gut microbiota to mitigate depression and improve mental health. While the interplay between microbial diversity, diet, and brain function offers promising therapeutic avenues, further clinical research is needed to validate these findings and establish robust, individualized treatment strategies.

It has been shown that the microflora of the gastrointestinal tract undergoes changes in obese individuals. The present study aimed to investigate the effect of kefir fortified with two strains, Lactobacillus helveticus and Bifidobacterium longum, on depression, appetite, oxidative stress, and inflammatory parameters in overweight and obese elderly individuals.

This study was a double-blind, randomized, and placebo-controlled clinical trial conducted on 67 elderly men aged over 65, who were randomly divided into two groups. One group (n = 35) received one bottle (240 cc) of regular kefir as a placebo, while the intervention group (n = 32) received one bottle of probiotic-fortified kefir for eight weeks. Depression and appetite were evaluated using the Geriatric Depression Scale-15 (GDS-15) and a validated Visual Analogue Scale (VAS), respectively. Oxidative stress parameters were assessed using the standard calorimetric method, and inflammatory parameters were measured via the enzyme-linked immunosorbent assay method (ELISA). The differences between the two groups were compared using the independent samples T-test.

The median age of participant in both groups was 65 years. A significant difference in depression scores and the mean change between the two groups was observed after eight weeks (p = 0.001 and p = 0.042, respectively). Within-group comparison revealed a significant increase in appetite scores in both groups (p < 0.05 for both). Moreover, a significant difference in the changes in total antioxidant capacity (TAC) was noted (p = 0.009). However, no significant differences were observed in other oxidative and inflammatory parameters between the two groups (p˃0.05 for all).

The results demonstrated the positive impact of two specific strains of Bifidobacterium and Lactobacillus on improving depression in the elderly. However, when comparing the two groups, no significant effects were observed on appetite, inflammation, and oxidative stress parameters, except for TAC.

The interplay between human health and the microbiome has gained extensive attention, with probiotics emerging as pivotal therapeutic agents due to their vast potential in treating various health issues. As significant modulators of the gut microbiota, probiotics are crucial in maintaining intestinal homeostasis and enhancing the synthesis of short-chain fatty acids. Despite extensive research over the past decades, there remains an urgent need for a comprehensive and detailed review that encapsulates probiotics' latest insights and applications. This review focusses on the multifaceted roles of probiotics in promoting health and preventing disease, highlighting the complex mechanisms through which these beneficial bacteria influence both gut flora and the human body at large. This paper also explores probiotics' neurological and gastrointestinal applications, focussing on their significant impact on the gut-brain axis and their therapeutic potential in a broad spectrum of pathological conditions. Current innovations in probiotic formulations, mainly focusing on integrating genomics and biotechnological advancements, have also been comprehensively discussed herein. This paper also critically examines the regulatory landscape that governs probiotic use, ensuring safety and efficacy in clinical and dietary settings. By presenting a comprehensive overview of recent studies and emerging trends, this review aims to illuminate probiotics' extensive therapeutic capabilities, leading to future research and clinical applications. However, besides extensive research, further advanced explorations into probiotic interactions and mechanisms will be essential for developing more targeted and effective therapeutic strategies, potentially revolutionizing health care practices for consumers.

Chronic stress often has deleterious effects leading to the development of psychiatric diseases. The gut-brain axis represents a novel avenue for stress research. The negative effects of stress on the gut physiology have been well-described, whereas the pathways whereby stress controls microbial composition to modulate behaviors remains mainly unknown. We discovered that vasoactive intestinal peptide (VIP) activation promoted stress-induced microbial changes leading to increased infiltration of T helper (Th) 17 cells and microglial activation in the hippocampus and depressive-like behaviors, uncovering a close crosstalk between intestinal VIPergic release and the gut microbiota during stress and providing a new interaction between the nervous system and the gut microbiome after stress. Neutralization of the signature cytokine of Th17 cells, interleukin (IL)-17A, was sufficient to block depressive-like behaviors, reduce neuronal VIPergic activation and microglia activation induced by VIPergic activation after stress, opening new potential therapeutic targets for depression.

Welfare in commercial livestock farming is becoming increasingly important in current agriculture research. Unfortunately, there is a lack of understanding about the neuronal mechanisms that underlie well-being on an individual level. Neuroplasticity in the hippocampus, the subventricular zone (SVZ), the olfactory bulb (OB) and the hypothalamus may be essential regulatory components in the context of farm animal behaviour and welfare that may be altered by providing environmental enrichment (EE). The importance of pre-and probiotics as a form of EE and the microbiota-gut-brain axis (MGBA) has come under the spotlight in the last 20 years, particularly in the contexts of research into stress and of stress resilience. However, it could also be an important regulatory system for animal welfare in livestock farming. This review aims to present a brief overview of the effects of EE on physiology and behaviour in farm animals and briefly discusses literature on behavioural flexibility, as well as inter-individual stress-coping styles and their relationship to animal welfare. Most importantly, we will summarise the literature on different forms of neural plasticity in farm animals, focusing on neurogenesis in various relevant brain regions. Furthermore, we will provide a brief outlook connecting these forms of neuroplasticity, stress, EE, the MGBA and welfare measures in modern livestock farming, concentrating on pigs.

Autism spectrum disorder is a neurodevelopmental disorder characterized by a wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism spectrum disorder, often proving ineffective and accompanied by a multitude of side effects. The gut microbiota is the reservoir of bacteria inhabiting our gastrointestinal tract. The gut microbial alterations observed in individuals with autism spectrum disorder, including elevated levels of Bacteroidetes, Firmicutes, and Proteobacteria, as well as reduced levels of Bifidobacterium, provide a basis for further investigation into the role of the gut microbiota in autism spectrum disorder. Recent preclinical studies have shown favorable outcomes with probiotic therapy, including improvements in oxidative stress, anti-inflammatory effects, regulation of neurotransmitters, and restoration of microbial balance. The aim of this review is to explore the potential of probiotics for the management and treatment of autism spectrum disorder, by investigating insights from recent studies in animals.

The pathogenesis of epilepsy is related to the microbiota-gut-brain axis, but the mechanism has not been clarified. The microbiota-gut-brain axis is divided into the microbiota-gut-brain axis (upward pathways) and the brain-gut-microbiota axis (downward pathways) according to the direction of conduction. Gut microorganisms are involved in pathological and physiological processes in the human body and participate in epileptogenesis through neurological, immunological, endocrine, and metabolic pathways, as well as through the gut barrier and blood brain barrier mediated upward pathways. After epilepsy, the downward pathway mediated by the HPA axis and autonomic nerves triggers "leaky brain "and "leaky gut," resulting in the formation of microbial structures and enterobacterial metabolites associated with epileptogenicity, re-initiating seizures via the upward pathway. Characteristic changes in microbial and metabolic pathways in the gut of epileptic patients provide new targets for clinical prevention and treatment of epilepsy through the upward pathway. Based on these changes, this review further redescribes the pathogenesis of epilepsy and provides a new direction for its prevention and treatment.

The primary objective of this study was to evaluate the effects of liquid (Fructose-added lactic acid bacteria, F-LAB) and commercial (Commercial LAB, C-LAB) probiotics sourced from Rye-Grass Lactic Acid Bacteria (LAB) on broiler chickens experiencing heat stress (HS). The research involved 240 broiler chicks, divided into six groups: control, F-LAB, C-LAB (raised at 24 °C), HS, F-LAB/HS, and C-LAB/HS (exposed to 5-7 h of 34-36 °C daily). The study followed a randomized complete block design, with each group consisting of 40 chicks. F-LAB and HS/F-LAB groups received a natural probiotic added to their drinking water at a rate of 0.5 ml/L, while C-LAB and HS/C-LAB groups were supplemented with a commercial probiotic at the same dosage. Control and HS groups received no probiotic supplementation. The duration of the study was 42 days, with data collected on growth performance, feed intake, feed conversion ratio, and health parameters. Statistical analyses were performed using ANOVA, and significant differences between groups were determined using post hoc tests. The results revealed that without probiotic supplementation, heat stress led to a decrease in body weight gain, T3 levels, citrulline, and growth hormone levels, along with an increase in the feed conversion ratio, serum corticosterone, HSP70, ALT, AST, and leptin levels (p < 0.05 for all). Heat stress also adversely affected cecal microbiota, reducing lactic acid bacteria count (LABC) while increasing Escherichia coli and coliform bacteria (CBC) counts. However, in the groups receiving probiotic supplementation under heat stress (F-LAB/HS and C-LAB/HS), these effects were alleviated (p < 0.05 for all). Particularly noteworthy was the observation that broiler chickens supplemented with natural lactic acid bacteria (F-LAB) exhibited greater resilience to heat stress compared to those receiving the commercial probiotic, as evidenced by improvements in growth, liver function, hormonal balance, intestinal health, and cecal microbiome ecology (p < 0.05). These findings suggest that the supplementation of naturally sourced probiotics (F-LAB) may positively impact the intestinal health of broiler chickens exposed to heat stress, potentially supporting growth and health parameters.

The widespread use of opioids for chronic pain management not only poses a significant public health issue but also contributes to the risk of tolerance, dependence, and addiction, leading to opioid use disorder (OUD), which affects millions globally each year. Recent research has highlighted a potential bidirectional relationship between the gut microbiome and OUD. This emerging perspective is critical, especially as the opioid epidemic intensifies, emphasizing the need to investigate how OUD may alter gut microbiome dynamics and vice versa. Understanding these interactions could reveal new insights into the mechanisms of addiction and tolerance, as well as provide novel approaches for managing and potentially mitigating OUD impacts. This comprehensive review explores the intricate bidirectional link through the gut-brain axis, focusing on how opiates influence microbial composition, functional changes, and gut mucosal integrity. By synthesizing current findings, the review aims to inspire new strategies to combat the opioid crisis and leverage microbiome-centred interventions for preventing and treating OUD.

This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.

In recent years, in-depth research has revealed that gut microbiota has an inseparable relationship with erectile dysfunction (ED) in men.

(1) To review the correlation between gut microbiota and ED from the perspective of its impact on men's mental health, metabolism, immunity, and endocrine regulation and (2) to provide reference to further explore the pathogenesis of ED and the improvement of clinical treatment plans.

PubMed was used for the literature search to identify publications related to ED and gut microbiota.

Gut microbiota may induce depression and anxiety through the microbiota-gut-brain axis, leading to the occurrence of psychological ED. It may also cause vascular endothelial dysfunction and androgen metabolism disorder by interfering with lipid metabolism, immunity, and endocrine regulation, leading to the occurrence of organic ED.

Gut microbiota and its metabolites play an important role in the occurrence and development of ED. As a new influencing factor of ED, gut microbiota disorder is expected to become a target for treatment.

Changes in maternal gut microbiota due to stress and/or ethanol exposure can have lasting effects on offspring's health, particularly regarding immunity, inflammation response, and susceptibility to psychiatric disorders. The literature search for this review was conducted using PubMed and Scopus, employing keywords and phrases related to maternal stress, ethanol exposure, gut microbiota, microbiome, gut-brain axis, diet, dysbiosis, progesterone, placenta, prenatal development, immunity, inflammation, and depression to identify relevant studies in both preclinical and human research. Only a limited number of reviews were included to support the arguments. The search encompassed studies from the 1990s to the present. This review begins by exploring the role of microbiota in modulating host health and disease. It then examines how disturbances in maternal microbiota can affect the offspring's immune system. The analysis continues by investigating the interplay between stress and dysbiosis, focusing on how prenatal maternal stress influences both maternal and offspring microbiota and its implications for susceptibility to depression. The review also considers the impact of ethanol consumption on gut dysbiosis, with an emphasis on the effects of prenatal ethanol exposure on both maternal and offspring microbiota. Finally, it is suggested that maternal gut microbiota dysbiosis may be significantly exacerbated by the combined effects of stress and ethanol exposure, leading to immune system dysfunction and chronic inflammation, which could increase the risk of depression in the offspring. These interactions underscore the potential for novel mental health interventions that address the gut-brain axis, especially in relation to maternal and offspring health.

Every facet of biological anthropology, including development, ageing, diseases, and even health maintenance, is influenced by gut microbiota's significant genetic and metabolic capabilities. With current advancements in sequencing technology and with new culture-independent approaches, researchers can surpass older correlative studies and develop mechanism-based studies on microbiome-host interactions. The microbiota-gut-brain axis (MGBA) regulates glial functioning, making it a possible target for the improvement of development and advancement of treatments for neurodegenerative diseases (NDDs). The gut-brain axis (GBA) is accountable for the reciprocal communication between the gastrointestinal and central nervous system, which plays an essential role in the regulation of physiological processes like controlling hunger, metabolism, and various gastrointestinal functions. Lately, studies have discovered the function of the gut microbiome for brain health-different microbiota through different pathways such as immunological, neurological and metabolic pathways. Additionally, we review the involvement of the neurotransmitters and the gut hormones related to gut microbiota. We also explore the MGBA in neurodegenerative disorders by focusing on metabolites. Further, targeting the blood-brain barrier (BBB), intestinal barrier, meninges, and peripheral immune system is investigated. Lastly, we discuss the therapeutics approach and evaluate the pre-clinical and clinical trial data regarding using prebiotics, probiotics, paraprobiotics, fecal microbiota transplantation, personalised medicine, and natural food bioactive in NDDs. A comprehensive study of the GBA will felicitate the creation of efficient therapeutic approaches for treating different NDDs.

The production of healthy food is one of the basic requirements and challenges. Research efforts have been introduced in the human's food industry to reduce the microbial resistance and use safe and healthy alternatives with a high durability. However, the conducted work about these issues in the field of livestock animal production have been started since 2015. Inappropriate and extensive use of antibiotics has resulted in the increase of antimicrobial resistance, presence of drug residues in tissues, and destruction of the gut microbiome. Therefore, discovering and developing antibiotic substitutes were urgent demands. Probiotic compounds containing living micro-organisms are important antibiotic alternative that have been beneficially and extensively used in humans, animals, and poultry. However, some probiotics show some obstacles during production and applications. Accordingly, this review article proposes a comprehensive description of the next-generation of probiotics including postbiotics, proteobiotics, psychobiotics, immunobiotics and paraprobiotics and their effects on poultry production and human's therapy. These compounds proved great efficiency in terms of restoring gut health, improving performance and general health conditions, modulating the immune response and reducing the pathogenic micro-organisms. However, more future research work should be carried out regarding this issue.

Post-stroke depression (PSD) is a psychological disease that can occur following a stroke and is associated with serious consequences. Research on the pathogenesis and treatment of PSD is still in the infancy stage. Patients with PSD often exhibit gastrointestinal symptoms; therefore the role of gut microbiota in the pathophysiology and potential treatment effects of PSD has become a hot topic of research. In this review, describe the research on the pathogenesis and therapy of PSD. We also describe how the gut microbiota influences neurotransmitters, the endocrine system, energy metabolism, and the immune system. It was proposed that the gut microbiota is involved in the pathogenesis and treatment of PSD through the regulation of neurotransmitter levels, vagal signaling, hypothalamic-pituitary-adrenal axis activation and inhibition, hormone secretion and release, in addition to immunity and inflammation.

Intestinal barrier is a first line of defense that prevents entry of various harmful substances from the lumen into the systemic environment. Impaired barrier function with consequent translocation of harmful substances into systemic circulation ("leaky gut") is a central theme in many gastrointestinal, autoimmune, mental, and metabolic diseases. Probiotics have emerged as a promising strategy to maintain intestinal integrity and address "leaky gut". Using in silico, in vitro and avian in vivo analyses, we previously showed that two novel L. reuteri strains, PTA-126787 (L. reuteri 3630) and PTA-126788 (L. reuteri 3632), isolated from broiler chickens possess favorable safety profiles. Consistent with a recent study, here we show that L. reuteri 3630 and 3632 are phylogenetically similar to human L. reuteri strains. Daily administration of high doses of L. reuteri 3630 and 3632 to Sprague Dawley rats for 28 days was found to be safe with no adverse effects. More importantly, administration of L. reuteri 3630 and 3632 significantly reduced markers associated with alcohol-induced leaky gut, by downregulating inflammatory cytokines and upregulating anti-inflammatory cytokines in an alcohol model of leaky gut in mice. While L. reuteri 3630 cells and supernatant showed no activation, L. reuteri 3632 cells but not supernatant showed activation of AhR, a key transcription factor that regulates gut and immune homeostasis. L. reuteri 3630 is creamish white in morphology typical of Lactobacillus species and L. reuteri 3632 displays a unique orange pigmentation, which was stable even after passaging for 480 generations. We identified a rare polyketide biosynthetic gene cluster in L. reuteri 3632 that likely encodes for the orange-pigmented secondary metabolite. Similar to L. reuteri 3632 cells, the purified orange metabolite activated AhR. All together, these data provide evidence on the phylogenetic relatedness, safety, efficacy, and one of the likely mechanisms of action of L. reuteri 3630 and 3632 for potential probiotic applications to address "leaky gut" and associated pathologies in humans.

The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota-host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions.

Some observational studies and clinical experiments suggest a close association between gut microbiota and metabolic diseases. However, the causal effects of gut microbiota on adrenal diseases, including Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism, remain unclear.

This study conducted a two-sample Mendelian randomization analysis using summary statistics data of gut microbiota from a large-scale genome-wide association study conducted by the MiBioGen Consortium. Summary statistics data for the three adrenal diseases were obtained from the FinnGen study. The study employed Inverse variance weighting, MR-Egger, and MR-PRESSO methods to assess the causal relationship between gut microbiota and these three adrenal diseases. Additionally, a reverse Mendelian randomization analysis was performed for bacteria found to have a causal relationship with these three adrenal diseases in the forward Mendelian randomization analysis. Cochran's Q statistic was used to test for heterogeneity of instrumental variables.

The IVW test results demonstrate that class Deltaproteobacteria, Family Desulfovibrionaceae, and Order Desulfovibrionales exhibit protective effects against adrenocortical insufficiency. Conversely, Family Porphyromonadaceae, Genus Lachnoclostridium, and Order MollicutesRF9 are associated with an increased risk of adrenocortical insufficiency. Additionally, Family Acidaminococcaceae confers a certain level of protection against Cushing syndrome. In contrast, Class Methanobacteria, Family Lactobacillaceae, Family Methanobacteriaceae, Genus. Lactobacillus and Order Methanobacteriales are protective against Hyperaldosteronism. Conversely, Genus Parasutterella, Genus Peptococcus, and Genus Veillonella are identified as risk factors for Hyperaldosteronism.

This two-sample Mendelian randomization analysis revealed a causal relationship between microbial taxa such as Deltaproteobacteria and Desulfovibrionaceae and Adrenocortical insufficiency, Cushing syndrome, and Hyperaldosteronism. These findings offer new avenues for comprehending the development of adrenal diseases mediated by gut microbiota.

The gastrointestinal (GI) tract and the brain form bidirectional nervous, immune, and endocrine communications known as the gut-brain axis. Several factors can affect this axis; among them, various studies have focused on the microbiota and imply that alterations in microbiota combinations can influence both the brain and GI. Also, many studies have shown that the immune system has a vital role in varying gut microbiota combinations. In the current paper, we will review the multidirectional effects of gut microbiota, immune system, and nervous system on each other. Specifically, this review mainly focuses on the impact of Peyer's patches as a critical component of the gut immune system on the gut-brain axis through affecting the gut's microbial composition. In this way, some factors were discussed as proposed elements of missing gaps in this field.

Depression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood.

We examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program.

We found that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1.

Our findings reveal a protective link between the Prevotella-dominant microbiome and depression, associated with a less inflammatory environment and moderated symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, highlight potential avenues for microbiome-targeted therapies in depression management.

Applications for plastic polymers can be found all around the world, often discarded without any prior care, exacerbating the environmental issue. When large waste materials are released into the environment, they undergo physical, biological, and photo-degradation processes that break them down into smaller polymer fragments known as microplastics (MPs). The time it takes for residual plastic to degrade depends on the type of polymer and environmental factors, with some taking as long as 600 years or more. Due to their small size, microplastics can contaminate food and enter the human body through food chains and webs, causing gastrointestinal (GI) tract pain that can range from local to systemic. Microplastics can also acquire hydrophobic organic pollutants and heavy metals on their surface, due to their large surface area and surface hydrophobicity. The levels of contamination on the microplastic surface are significantly higher than in the natural environment. The gut-brain axis (GB axis), through which organisms interact with their environment, regulate nutritional digestion and absorption, intestinal motility and secretion, complex polysaccharide breakdown, and maintain intestinal integrity, can be altered by microplastics acting alone or in combination with pollutants. Probiotics have shown significant therapeutic potential in managing various illnesses mediated by the gut-brain axis. They connect hormonal and biochemical pathways to promote gut and brain health, making them a promising therapy option for a variety of GB axis-mediated illnesses. Additionally, taking probiotics with or without food can reduce the production of pro-inflammatory cytokines, reactive oxygen species (ROS), neuro-inflammation, neurodegeneration, protein folding, and both motor and non-motor symptoms in individuals with Parkinson's disease. This study provides new insight into microplastic-induced gut dysbiosis, its associated health risks, and the benefits of using both traditional and next-generation probiotics to maintain gut homeostasis.

Prebiotics are non-digestible ingredients that exert significant health-promoting effects on hosts. Galactooligosaccharides (GOS) have remarkable prebiotic effects and structural similarity to human milk oligosaccharides. They generally comprise two to eight sugar units, including galactose and glucose, which are synthesized from substrate lactose by microbial β-galactosidase. Enzyme sources from probiotics have received particular interest because of their safety and potential to synthesize specific structures that are particularly metabolized by intestinal probiotics. Owing to advancements in modern analytical techniques, many GOS structures have been identified, which vary in degree of polymerization, glycosidic linkage, and branch location. After intake, GOS adjust gut microbiota which produce short chain fatty acids, and exhibit excellent biological activities. They selectively stimulate the proliferation of probiotics, inhibit the growth and adhesion of pathogenic bacteria, alleviate gastrointestinal, neurological, metabolic and allergic diseases, modulate metabolites production, and adjust ion storage and absorption. Additionally, GOS are safe and stable, with high solubility and clean taste, and thus are widely used as food additives. GOS can improve the appearance, flavor, taste, texture, viscosity, rheological properties, shelf life, and health benefits of food products. This review systemically covers GOS synthesis, structure identifications, metabolism mechanisms, prebiotic bioactivities and wide applications, focusing on recent advances.

In recent years, an increasing attention has given to the intricate and diverse connection of microorganisms residing in our gut and their impact on brain health and central nervous system disease. There has been a shift in mindset to understand that drug addiction is not merely a condition that affects the brain, it is now being recognized as a disorder that also involves external factors such as the intestinal microbiota, which could influence vulnerability and the development of addictive behaviors. Furthermore, stress and social interactions, which are closely linked to the intestinal microbiota, are powerful modulators of addiction. This review delves into the mechanisms through which the microbiota-stress-immune axis may shape drug addiction and social behaviors. This work integrates preclinical and clinical evidence that demonstrate the bidirectional communication between stress, social behaviors, substance use disorders and the gut microbiota, suggesting that gut microbes might modulate social stress having a significance in drug addiction.

Chronic stress disrupts microbiota-gut-brain axis function and is associated with altered tryptophan metabolism, impaired gut barrier function, and disrupted diurnal rhythms. However, little is known about the effects of acute stress on the gut and how it is influenced by diurnal physiology. Here, we used germ-free and antibiotic-depleted mice to understand how microbiota-dependent oscillations in tryptophan metabolism would alter gut barrier function at baseline and in response to an acute stressor. Cecal metabolomics identified tryptophan metabolism as most responsive to a 15-min acute stressor, while shotgun metagenomics revealed that most bacterial species exhibiting rhythmicity metabolize tryptophan. Our findings highlight that the gastrointestinal response to acute stress is dependent on the time of day and the microbiome, with a signature of stress-induced functional alterations in the ileum and altered tryptophan metabolism in the colon.

Alzheimer's disease (AD) is a neurodegenerative disorder marked by neuroinflammation and gradual cognitive decline. Recent research has revealed that the gut microbiota (GM) plays an important role in the pathogenesis of AD through the microbiota-gut-brain axis. However, the mechanism by which GM and microbial metabolites alter brain function is not clearly understood. GM dysbiosis increases the permeability of the intestine, alters the blood-brain barrier permeability, and elevates proinflammatory mediators causing neurodegeneration. This review article introduced us to the composition and functions of GM along with its repercussions of dysbiosis in relation to AD. We also discussed the importance of the gut-brain axis and its role in communication. Later we focused on the mechanism behind gut dysbiosis and the progression of AD including neuroinflammation, oxidative stress, and changes in neurotransmitter levels. Furthermore, we highlighted recent developments in AD management, such as microbiota-based therapy, dietary interventions like prebiotics, probiotics, and fecal microbiota transplantation. Finally, we concluded with challenges and future directions in AD research based on GM.

Although there is little direct evidence supporting that stress affects cancer incidence, it does influence the evolution, dissemination and therapeutic outcomes of neoplasia, as shown in human epidemiological analyses and mouse models. The experience of and response to physiological and psychological stressors can trigger neurological and endocrine alterations, which subsequently influence malignant (stem) cells, stromal cells and immune cells in the tumour microenvironment, as well as systemic factors in the tumour macroenvironment. Importantly, stress-induced neuroendocrine changes that can regulate immune responses have been gradually uncovered. Numerous stress-associated immunomodulatory molecules (SAIMs) can reshape natural or therapy-induced antitumour responses by engaging their corresponding receptors on immune cells. Moreover, stress can cause systemic or local metabolic reprogramming and change the composition of the gastrointestinal microbiota which can indirectly modulate antitumour immunity. Here, we explore the complex circuitries that link stress to perturbations in the cancer-immune dialogue and their implications for therapeutic approaches to cancer.