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Increasing evidence suggests that the gut microbiome plays a key role in a host of pathological conditions, including cancer. Indeed, the bidirectional communication that occurs between the gut and the brain, known as the 'gut-brain axis,' has recently been implicated in brain tumour pathology. Here, we focus on current research that supports a gut microbiome-brain tumour link with emphasis on high-grade gliomas, the most aggressive of all brain tumours, and the impact on the glioma tumour microenvironment. We discuss the potential use of gut-brain axis signals to improve responses to current and future therapeutic approaches. We highlight that the success of novel treatment strategies may rely on patient-specific microbiome profiles, and these should be considered for personalised treatment approaches.

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The gut-brain axis (GBA) is a crucial communication network linking the gastrointestinal (GI) tract and the central nervous system (CNS). The gut microbiota significantly influences metabolic, immune, and neural functions by generating a diverse array of bioactive compounds that modulate brain function and maintain homeostasis. A pivotal mechanism in this communication is the kynurenine pathway, which metabolises tryptophan into various derivatives, including neuroactive and neurotoxic compounds. Alterations in gut microbiota composition can increase gut permeability, triggering inflammation and neuroinflammation, and contributing to neuropsychiatric disorders. This review elucidates the mechanisms by which changes in gut permeability may lead to systemic inflammation and neuroinflammation, with a focus on the kynurenine pathway. We explore how probiotics can modulate the kynurenine pathway and reduce neuroinflammation, highlighting their potential as therapeutic interventions for neuropsychiatric disorders. The review integrates experimental data, discusses the balance between neurotoxic and neuroprotective kynurenine metabolites, and examines the role of probiotics in regulating inflammation, cognitive development, and gut-brain axis functions. The insights provided aim to guide future research and therapeutic strategies for mitigating GI complaints and their neurological consequences.

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Background: Insomnia persists as a prevalent sleep disorder among middle-aged and older adults, significantly impacting quality of life and increasing susceptibility to age-related diseases. It is classified into objective insomnia (O-IN) and paradoxical insomnia (P-IN), where subjective and objective sleep assessments diverge. Current treatment regimens for both patient groups yield unsatisfactory outcomes. Consequently, investigating the neurophysiological distinctions between P-IN and O-IN is imperative for devising novel precision interventions aligned with primary prediction, targeted prevention, and personalized medicine (PPPM) principles.Working hypothesis and methodology.Given the emerging influence of gut microbiota (GM) on sleep physiology via the gut-brain axis, our study focused on characterizing the GM profiles of a well-characterized cohort of 96 Italian postmenopausal women, comprising 54 insomniac patients (18 O-IN and 36 P-IN) and 42 controls, through 16S rRNA amplicon sequencing. Associations were explored with general and clinical history, sleep patterns, stress, hematobiochemical parameters, and nutritional patterns. Results: Distinctive GM profiles were unveiled between O-IN and P-IN patients. O-IN patients exhibited prominence in the Coriobacteriaceae family, including Collinsella and Adlercreutzia, along with Erysipelotrichaceae, Clostridium, and Pediococcus. Conversely, P-IN patients were mainly discriminated by Bacteroides, Staphylococcus, Carnobacterium, Pseudomonas, and respective families, along with Odoribacter. Conclusions: These findings provide valuable insights into the microbiota-mediated mechanism of O-IN versus P-IN onset. GM profiling may thus serve as a tailored stratification criterion, enabling the identification of women at risk for specific insomnia subtypes and facilitating the development of integrated microbiota-based predictive diagnostics, targeted prevention, and personalized therapies, ultimately enhancing clinical effectiveness. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00369-1.

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Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.

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BACKGROUND: Major depressive disorder (MDD) is a severe mental health condition characterized by persistent depression, impaired cognition, and reduced activity. Increasing evidence suggests that gut microbiota (GM) imbalance is closely linked to the emergence and advancement of MDD, highlighting the potential significance of regulating the "Microbiota-Gut-Brain" (MGB) axis to impact the development of MDD. Natural products (NPs), characterized by broad biological activities, low toxicity, and multi-target characteristics, offer unique advantages in antidepressant treatment by regulating MGB axis. PURPOSE: This review was aimed to explore the intricate relationship between the GM and the brain, as well as host responses, and investigated the mechanisms underlying the MGB axis in MDD development. It also explored the pharmacological mechanisms by which NPs modulate MGB axis to exert antidepressant effects and addressed current research limitations. Additionally, it proposed new strategies for future preclinical and clinical applications in the MDD domain. METHODS: To study the effects and mechanism by which NPs exert antidepressant effects through mediating the MGB axis, data were collected from Web of Science, PubMed, ScienceDirect from initial establishment to March 2024. NPs were classified and summarized by their mechanisms of action. RESULTS: NPs, such as flavonoids,alkaloids,polysaccharides,saponins, terpenoids, can treat MDD by regulating the MGB axis. Its mechanism includes balancing GM, regulating metabolites and neurotransmitters such as SCAFs, 5-HT, BDNF, inhibiting neuroinflammation, improving neural plasticity, and increasing neurogenesis. CONCLUSIONS: NPs display good antidepressant effects, and have potential value for clinical application in the prevention and treatment of MDD by regulating the MGB axis. However, in-depth study of the mechanisms by which antidepressant medications affect MGB axis will also require considerable effort in clinical and preclinical research, which is essential for the development of effective antidepressant treatments.

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The sedative and hypnotic properties of 5,7,3',4',5'-pentamethoxyflavone (PMF), a monomer extracted from the leaves of Murraya paniculata (L.) Jack, have been reported. However, the role of PMFs in the development of anxiety remains uncertain. An anxiety model was developed using chronic unpredictable mild stimulation (CUMS). Kunming mice were randomly allocated to the following groups: control, CUMS, PMF (50 mg/kg), PMF (100 mg/kg), and diazepam (3 mg/kg). The anxiolytic effects of PMFs were evaluated using elevated plus maze (EPM) test and open field test (OFT). Enzyme-linked immunosorbent assay (ELISA) kits were used to analyze the serum levels of corticosterone (CORT), 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), and cyclic adenosine monophosphate (cAMP) in the hippocampus. High-throughput-16S rRNA sequencing was performed to investigate its effect on the composition of the gut microbiota. Subsequently, western blotting was performed to assess the expression of GABAergic synaptic-associated proteins. PMF effectively mitigated CUMS-induced anxiety-like behavior. Further examination revealed that PMF treatment ameliorated dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and increased 5-HT and GABA levels in the hippocampus. Notably, the ability of PMF to maintain the stability of GABAergic synapses by enhancing the species composition of the gut microbiota and acting on the adenosine a2a receptor (A2AR)/gephyrin/gamma-aminobutyric acid A receptor alpha 2 (GABRA2) pathway revealed a previously unrecognized mechanism for the anxiolytic effect of PMF. These findings suggest that PMF enhances the expression of A2AR, preserves GABAergic synaptic stability, and reduces anxiety by modulating the microbiota composition. Thus, it holds promise as an anxiolytic agent.

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In the human body, eukaryotic somatic cells and prokaryotic microorganisms live together. In this state, the body can be viewed as a "superorganism." Symbiotic life with commensal microorganisms can be observed in almost every part of the body. Intestinal microbiota plays an important role in health and disease, and in shaping and regulating neuronal functions from the intrauterine period to the end of life. Microbiota-based treatment opportunities are becoming more evident in both understanding the etiopathogenesis and treatment of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first choice in the treatment of depression, also have antimicrobial and immunomodulatory mechanisms of action. From these perspectives, direct probiotics and fecal microbiota transplantation are treatment options to modulate microbiota composition. There are few preclinical and clinical studies on the effectiveness and safety of these applications in depression. The information obtained from these studies may still be at a doxa level. However, the probability that this information will become episteme in the future seems to be increasing.

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Severe toxic effects of arsenic on human physiology have been of immense concern worldwide. Arsenic causes irrevocable structural and functional disruption of tissues, leading to major diseases in chronically exposed individuals. However, it is yet to be resolved whether the effects result from direct deposition and persistence of arsenic in tissues, or via activation of indirect signaling components. Emerging evidences suggest that gut inhabitants play an active role in orchestrating various aspects of brain physiology, as the gut-brain axis maintains cognitive health, emotions, learning and memory skills. Arsenic-induced dysbiosis may consequentially evoke neurotoxicity, eventually leading to anxiety and depression. To delineate the mechanism of action, mice were exposed to different concentrations of arsenic. Enrichment of Gram-negative bacteria and compromised barrier integrity of the gut enhanced lipopolysaccharide (LPS) level in the bloodstream, which in turn elicited systemic inflammation. Subsequent alterations in neurotransmitter levels, microglial activation and histoarchitectural disruption in brain triggered onset of anxiety- and depression-like behaviour in a dose-dependent manner. Finally, to confirm whether the neurotoxic effects are specifically a consequence of modulation of gut microbiota (GM) by arsenic and not arsenic accumulation in the brain, fecal microbiota transplantations (FMT) were performed from arsenic-exposed mice to healthy recipients. 16S rRNA gene sequencing indicated major alterations in GM population in FMT mice, leading to severe structural, functional and behavioural alterations. Moreover, suppression of Toll-like receptor 4 (TLR4) using vivo-morpholino oligomers (VMO) indicated restoration of the altered parameters towards normalcy in FMT mice, confirming direct involvement of the GM in inducing neurotoxicity through the arsenic-gut-brain axis. This study accentuates the potential role of the gut microbiota in promoting neurotoxicity in arsenic-exposed mice, and has immense relevance in predicting neurotoxicity under altered conditions of the gut for designing therapeutic interventions that will target gut dysbiosis to attenuate arsenic-mediated neurotoxicity.

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Disgust is a vital emotion in the avoidance of illness. Human adults across cultures show disgust towards sources of potential contamination or pathogens, and elect to avoid their ingestion or even to look at them. Stomach rhythms appear to play an important role: disgust reduces normogastric power, and the pharmacological normalisation of gastric state reduces disgust avoidance. Human children are remarkably slow to develop disgust as measured by self-report and facial expressions. Here, we investigate whether disgust-induced avoidance (measured using eye tracking) and changes in gastric rhythm (measured using electrogastrography) exist in children aged 5 to 13 years (N = 45). We found that children in this bracket showed oculomotor avoidance of disgusting stimuli in a preferential-looking task, similar to adult samples in previous research. However, in contrast to adult samples in previous research, children did not show an attenuation in normogastric power. These findings could suggest that avoidance behaviour precedes gastric involvement during disgust. This would support the idea that children initially respond to parental modelling: parents set (and enforce) the social norm of disgust avoidance, and children initially conform and only later do they internalise disgust as an interoceptive signal. Alternatively, the employed stimuli could have been potent enough to induce oculomotor avoidance, but not a gastric response. Research is slim in this area, and future work should focus on elucidating the role of the stomach in disgust, and on longitudinal studies of disgust development from childhood to adolescence.

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Neurodegenerative disorders are the main cause of cognitive and physical disabilities, affect millions of people worldwide, and their incidence is on the rise. Emerging evidence pinpoints a disturbance of the communication of the gut-brain axis, and in particular to gut microbial dysbiosis, as one of the contributors to the pathogenesis of these diseases. In fact, dysbiosis has been associated with neuro-inflammatory processes, hyperactivation of the neuronal immune system, impaired cognitive functions, aging, depression, sleeping disorders, and anxiety. With the rapid advance in metagenomics, metabolomics, and big data analysis, together with a multidisciplinary approach, a new horizon has just emerged in the fields of translational neurodegenerative disease. In fact, recent studies focusing on taxonomic profiling and leaky gut in the pathogenesis of neurodegenerative disorders are not only shedding light on an overlooked field but are also creating opportunities for biomarker discovery and development of new therapeutic and adjuvant strategies to treat these disorders. Lactiplantibacillus plantarum (LBP) strains are emerging as promising psychobiotics for the treatment of these diseases. In fact, LBP strains are able to promote eubiosis, increase the enrichment of bacteria producing beneficial metabolites such as short-chain fatty acids, boost the production of neurotransmitters, and support the homeostasis of the gut-brain axis. In this review, we summarize the current knowledge on the role of the gut microbiota in the pathogenesis of neurodegenerative disorders with a particular focus on the benefits of LBP strains in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism, anxiety, and depression.

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Globally, irritable bowel syndrome (IBS) is present in approximately 10% of the population. While this condition does not pose a risk of complications, it has a substantial impact on the patient's quality of life. Moreover, this disease has a significant financial impact on healthcare systems. This includes the direct costs associated with the diagnosis and treatment of these patients, as well as the indirect costs that arise from work absenteeism and reduced productivity. In light of these data, recent research has focused on elucidating the pathophysiological basis of this condition in order to improve the quality of life for affected individuals. Despite extensive research to date, we still do not fully understand the precise mechanisms underlying IBS. Numerous studies have demonstrated the involvement of the gut-brain axis, visceral hypersensitivity, gastrointestinal dysmotility, gut microbiota dysbiosis, food allergies and intolerances, low-grade mucosal inflammation, genetic factors, and psychosocial factors. The acquisition of new data is crucial for the advancement of optimal therapeutic approaches aimed at enhancing the general health of these patients while simultaneously reducing the financial burden associated with this ailment.

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Elevated levels of glial fibrillary acidic protein (GFAP) in plasma reflect neuroinflammation and are linked to cognitive decline. Preclinical studies show that dietary change can attenuate astrocyte reactivity and neuroinflammation. In the current study, we investigate if the Okinawa-based Nordic (O-BN) diet alters plasma GFAP levels in patients with Type 2 Diabetes (T2D), a metabolic disorder associated with cognitive disturbances and an increased risk of dementia. Plasma GFAP levels were measured in T2D patients (n = 30) at baseline, after 3 months of the diet, and after a subsequent 4 months of unrestricted diets. The GFAP levels decreased significantly after 3 months of the diet (p = 0.048) but reverted to baseline levels after 4 months of unrestricted diets. At baseline, the GFAP levels correlated significantly with levels of the neurodegeneration marker neurofilament light polypeptide (r = 0.400*) and, after correcting for age, sex, and body mass index, with proinflammatory plasma cytokines (ranging from r = 0.440* to r = 0.530**) and the metabolic hormone islet amyloid polypeptide (r = 0.478*). We found no correlation with psychological well-being. These results suggest that the O-BN diet reduces neuroinflammation in T2D patients and may thus be an important preventive measure for managing T2D and reducing the risk of neurodegenerative disorders.

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The long-term high-fat, high-sugar diet exacerbates type 2 diabetes mellitus (T2DM)-related cognitive impairments. Phlorizin, a well-studied natural compound found in apples and other plants, is recognized for its bioactive properties, including modulation of glucose and lipid metabolism. Despite its established role in mitigating metabolic disorders, the neuroprotective effects of phlorizin, particularly against diabetes-related cognitive dysfunction, have not been fully elucidated. Therefore, the present study aimed to investigate the effect of dietary supplementation of phlorizin on high-fat and high-fructose diet (HFFD)-induced cognitive dysfunction and evaluate the crucial role of the microbiota-gut-brain axis. We found that dietary supplementation of phlorizin for 14 weeks effectively prevented glucolipid metabolism disorder, spatial learning impairment, and memory impairment in HFFD mice. In addition, phlorizin improved the HFFD-induced decrease in synaptic plasticity, neuroinflammation, and excessive activation of microglia in the hippocampus. Transcriptomics analysis shows that the protective effect of phlorizin on cognitive impairment was associated with increased expression of neurotransmitters and synapse-related genes in the hippocampus. Phlorizin treatment alleviated colon microbiota disturbance, mainly manifested by an increase in gut microbiota diversity and the abundance of short-chain fatty acid (SCFA)-producing bacteria. The level of microbial metabolites, including SCFA, inosine 5'-monophosphate (IMP), and D (-)-beta-hydroxybutyric acid (BHB) were also significantly increased after phlorizin treatment. Integrating multiomics analysis observed tight connections between phlorizin-regulated genes microbiota, and metabolites. Furthermore, removal of the gut microbiota via antibiotics treatment diminished the protective effect of phlorizin against HFFD-induced cognitive impairment, underscoring the critical role of the gut microbiota in mediating cognitive behavior. Importantly, supplementation with SCFA and BHB alone mimicked the regulatory effects of phlorizin on cognitive function. Therefore phlorizin shows promise as a potential nutritional therapy for addressing cognitive impairment associated with metabolic disorders. Further research is needed to explore its effectiveness in preventing and alleviating neurodegenerative diseases.

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BACKGROUND: Ischemic stroke belongs to "apoplexy" and its pathogenesis is characterized by qi deficiency and blood stasis combining with phlegm-damp clouding orifices. Buqi-Huoxue-Tongnao decoction (BHTD) is a traditional Chinese medicine formula for qi deficiency, blood stasis and phlegm obstruction syndrome. However, its efficacy and potential mechanism on ischemic stroke are still unclear. This study aims to investigate the protective effect and potential mechanism of BHTD against ischemic stroke. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) surgery was carried out to establish an ischemic stroke model in rats. Subsequently, the rats were gavaged with different doses of BHTD (2.59, 5.175, 10.35 g/kg) for 14 days. The protective effects of BHTD on the brain and gut were evaluated by neurological function scores, cerebral infarction area, levels of brain injury markers (S-100B, NGB), indicators of gut permeability (FD-4) and bacterial translocation (DAO, LPS, D-lactate), and tight junction proteins (Occludin, Claudin-1, ZO-1) in brain and colon. 16S rRNA gene sequencing and metabolomic analysis were utilized to analyze the effects on gut microecology and screen for marker metabolites to explore potential mechanisms of BHTD protection against ischemic stroke. RESULTS: BHTD could effectively mitigate brain impairment, including reducing neurological damage, decreasing cerebral infarction and repairing the blood-brain barrier, and BHTD showed the best effect at the dose of 10.35 g/kg. Moreover, BHTD reversed gut injury induced by ischemic stroke, as evidenced by decreased intestinal permeability, reduced intestinal bacterial translocation, and enhanced intestinal barrier integrity. In addition, BHTD rescued gut microbiota dysbiosis by increasing the abundance of beneficial bacteria, including Turicibacter and Faecalibaculum. Transplantation of the gut microbiota remodeled by BHTD into ischemic stroke rats recapitulated the protective effects of BHTD. Especially, BHTD upregulated tryptophan metabolism, which promoted gut microbiota to produce more indole lactic acid (ILA). Notably, supplementation with ILA by gavage could alleviate stroke injury, which suggested that driving the production of ILA in the gut might be a novel treatment for ischemic stroke. CONCLUSION: BHTD could increase gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis. Our current finding provides evidence that traditional Chinese medicine can ameliorate central diseases through regulating the gut microbiology.

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BACKGROUND: The significant morbidity and mortality rates of acute intracerebral hemorrhage (ICH) are well-known around the world. The link between gut microbiota and different types of strokes is becoming more studied. The goal of this study was to look at the relationships between intestinal flora and early-stage mild-to-moderate ICH (emICH), and to provide a new perspective for adjunctive treatment of emICH. METHODS: Fecal samples from 100 participants with emICH (n=50) and healthy individuals (n=50) in this study were collected as well as analyzed utilizing 16S rRNA gene amplicon sequencing in order to characterize the gut microbial community. RESULTS: Distinct microbial communities are present within each group, with emICH patients exhibiting a diminished diversity and uniformity in their microbial profiles. A notable shift in the gut microbiota composition of emICH patients has been observed, characterized by an upsurge in pro-inflammatory microbes belonging to the Euryarchaeota phylum and a concurrent decline in beneficial Bacteroidetes species. Concurrently, significant associations and patterns among operational taxonomic units (OTUs) were identified in emICH patients. A panel of biomarkers (WAL_1855D, Methanobrevibacter, Streptococcus, Bacteroides, Coprococcus, Lachnospira) has been effectively utilized to distinguish emICH patients from healthy individuals, with an area under the curve (AUC) of 0.845. Additionally, an analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation uncovered several perturbed pathways in emICH patients, predominantly those related to metabolic processes and the inflammatory response. Moreover, predictive profiling of the microbiome's phenotypic traits suggests that emICH patients are likely to harbor a higher prevalence of Gram-negative bacteria and potential opportunistic pathogens compared to healthy controls. CONCLUSIONS: The gut microbiota ecosystem of emICH patients is disrupted, characterized primarily by an increase in pro-inflammatory microbiota, elevated inflammatory signaling pathways, and metabolic dysregulation. Furthermore, microbiota modulation may be seen as a novel approach for the adjunctive treatment of emICH.

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The organic anion transporters, OAT1 and OAT3, regulate the movement of drugs, toxins, and endogenous metabolites. In 2006, we proposed that OATs and other SLC22 transporters are involved in "remote sensing" and organ crosstalk. This is now known as the Remote Sensing and Signaling Theory (RSST). In the proximal tubule of the kidney, OATs regulate signaling molecules such as fatty acids, bile acids, indoxyl sulfate, kynurenine, alpha-ketoglutarate, urate, flavonoids, and antioxidants. OAT1 and OAT3 function as key hubs in a large homeostatic network involving multi-, oligo- and monospecific transporters, enzymes, and nuclear receptors. The RSST emphasizes the functioning of OATs and other "drug" transporters in the network at multiple biological scales (inter-organismal, organism, organ, cell, organelle). This network plays an essential role in the homeostasis of urate, bile acids, prostaglandins, sex steroids, odorants, thyroxine, gut microbiome metabolites, and uremic toxins. The transported metabolites have targets in the kidney and other organs, including nuclear receptors (e.g., HNF4a, AHR), G protein-coupled receptors (GPCRs), and protein kinases. Feed-forward and feedback loops allow OAT1 and OAT3 to mediate organ crosstalk as well as modulate energy metabolism, redox state, and remote sensing. Furthermore, there is intimate inter-organismal communication between renal OATs and the gut microbiome. Extracellular vesicles containing microRNAs and proteins (exosomes) play a key role in the Remote Sensing and Signaling System as well does the interplay with the neuroendocrine, hormonal, and immune systems. Perturbation of function with OAT-interacting drugs (e.g., probenecid, diuretics, antivirals, antibiotics, NSAIDs) can lead to drug-metabolite interactions. The RSST has general applicability to other multi-specific SLC and ABC "drug" transporters (e.g., OCT1, OCT2, SLCO1B1, SLCO1B3, ABCG2, P-gp, ABCC2, ABCC3, ABCC4). Recent high-resolution structures of SLC22 and other transporters, together with chemoinformatic and artificial intelligence methods, will aid drug development and also lead to a deeper mechanistic understanding of polymorphisms.

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BACKGROUND: Human milk oligosaccharides (HMOs), which are unique bioactive components in human milk, are increasingly recognized for their multifaceted roles in infant health. A deeper understanding of the nexus between HMOs and the gut-brain axis can revolutionize neonatal nutrition and neurodevelopmental strategies. METHODS: We performed a narrative review using PubMed, Embase, and Google Scholar to source relevant articles. The focus was on studies detailing the influence of HMOs on the gut and brain systems, especially in neonates. Articles were subsequently synthesized based on their exploration into the effects and mechanisms of HMOs on these interconnected systems. RESULTS: HMOs significantly influence the neonatal gut-brain axis. Specific concentrations of HMO, measured 1 and 6 months after birth, would seem to agree with this hypothesis. HMOs are shown to influence gut microbiota composition and enhance neurotransmitter production, which are crucial for brain development. For instance, 2'-fucosyllactose has been demonstrated to support cognitive development by fostering beneficial gut bacteria that produce essential short-chain fatty acids. CONCLUSIONS: HMOs serve as crucial modulators of the neonatal gut-brain axis, underscoring their importance in infant nutrition and neurodevelopment. Their dual role in shaping the infant gut while influencing brain function presents them as potential game-changers in neonatal health strategies.

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From Italian physician Hieronymus Mercurialis's contention that the stomach was 'the king of the belly', to its promotion by the end of the nineteenth century to the 'monarch of humanity' in patent medicine, to Byron Robinson's discovery of the enteric nervous system in 1907 (a mesh of neural connectivity that led him to dub the gut 'the second brain'), there has historically been a longstanding awareness of the expansive reach of the gut in the functions of the body. In the nineteenth century, the authority of the gut and its allyship with the brain became a focus for writers thinking about the intersections of illness and 'modern life'. In medical texts, domestic health manuals, patent medicine, and fiction, the electric telegraph in particular became a way of envisaging what we would now call the 'gut-brain axis'. The telegraphic metaphor enabled a view of digestion as not simply a mechanical or chemical process, but one that was understood in terms of time, space, and communication. However, such a framework also suggested problems of connection that were common to both systems, emphasising not only the healthy body's quasi-telegraphic networks but also its vulnerability to delay, disruption, and pathological incoherence. This article will explore the use of telegraphic technologies as proxies for theorising gastric connection and more broadly the concept of 'gastric time' as a key conceit for understanding digestion as a process that was and is subject to the idiosyncrasies of bodily rhythms.

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Microglia are macrophage cells residing in the brain, where they exert a key role in neuronal protection. Through the gut-brain axis, metabolites produced by gut commensal microbes can influence brain functions, including microglial activity. The nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the oxidative stress response in microglia, controlling the expression of cytoprotective genes. Lactobacilli-derived cell-free supernatants (CFSs) are postbiotics that have shown antioxidant and immunomodulatory effects in several in vitro and in vivo studies. This study aimed to explore the effects of lactobacilli CFSs on modulating microglial responses against oxidative stress and inflammation. HMC3 microglia were exposed to lipopolysaccaride (LPS), as an inflammatory trigger, before and after administration of CFSs from three human gut probiotic species. The NRF2 nuclear protein activation and the expression of NRF2-controlled antioxidant genes were investigated by immunoassay and quantitative RT-PCR, respectively. Furthermore, the level of pro- and anti-inflammatory cytokines was evaluated by immunoassay. All CFSs induced a significant increase of NRF2 nuclear activity in basal conditions and upon inflammation. The transcription of antioxidant genes, namely heme oxygenase 1, superoxide dismutase (SOD), glutathione-S transferase, glutathione peroxidase, and catalase also increased, especially after inflammatory stimulus. Besides, higher SOD1 activity was detected relative to inflamed microglia. In addition, CFSs pre-treatment of microglia attenuated pro-inflammatory TNF-α levels while increasing anti-inflammatory IL-10 levels. These findings confirmed that gut microorganisms' metabolites can play a relevant role in adjuvating the microglia cellular response against neuroinflammation and oxidative stress, which are known to cause neurodegenerative diseases.

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Background: There are few efficient treatment options for alcohol addiction, which continues to be a serious public health concern. The possible contribution of gut microbiota to the onset and progression of alcohol addiction has been brought to light by recent studies. Probiotics have become a cutting-edge intervention in the treatment of alcohol consumption disorder because of its favorable effects on gut health. The purpose of this systematic review is to assess the body of research on the advantages of probiotics in treating alcoholism and associated neuroinflammatory conditions. Methods: To find pertinent research published from January 2012 to 2023, a thorough search of electronic databases, including PubMed, Scopus, Google Scholar and Web of Science, was carried out. Included were studies looking at how probiotics affect neuroinflammation, gut- brain axis regulation, alcohol addiction, and related behaviors. Findings: Several investigations have shown how beneficial probiotics are in reducing systemic inflammation and alcoholic liver disease (ALD). Probiotic treatments successfully corrected the imbalance of microbiota, decreased intestinal permeability, and stopped the passage of bacterial constituents such lipopolysaccharides (LPS) into the bloodstream. Additionally, probiotics helped to regulate neurotransmitter pathways, especially those connected to GABA, glutamate, and dopamine, which are intimately linked to behaviors related to addiction. Furthermore, it was shown that probiotics altered the expression of neurotransmitter signaling and dopamine receptors. Conclusion: There is strong evidence from this systematic study that probiotics have potential advantages in treating alcohol addiction. The potential of probiotic therapies is demonstrated by the way they modulate important neurotransmitter pathways implicated in addiction, decrease neuroinflammation, and restore the balance of gut flora. To fully investigate the therapeutic potential of probiotics in treating alcohol addiction and enhancing the general wellbeing of those afflicted by this condition, more research is necessary.