Probiotics comprise various strains that offer numerous health benefits. Researchers have recently focused on the relationship between probiotic consumption and improved gut microbiota function, enhanced digestion, increased nutrient absorption, and enhanced sports performance. Therefore, the present study investigated the effects of pre-sleep casein intake, coupled with probiotic strains, on soccer players' anaerobic power, lower-body-specific strength, and power performance.

A randomized, double-blinded, and placebo-controlled study was conducted with forty-four male soccer players (Age: 22.81 ± 2.76 years, Height: 177.90 ± 6.75 cm, Weight: 67.42 ± 8.44 kg). The participants underwent the isokinetic strength, Wall-squat, and running-based anaerobic sprint (RAST) tests initially; then, they were randomly divided into four groups: probiotics (PRO), casein (CAS), probiotics with casein (PRO+CAS), and placebo (PLA). The PRO groups were given one probiotic capsule (containing eight bacterial strains: Lactiplantibacillus plantarum BP06, Lacticaseibacillus casei BP07, Lactobacillus acidophilus BA05, Lactobacillus bulgaricus BD08, Bifidobacterium infantis BI04, Bifidobacterium longum BL03, Bifidobacterium breve BB02, and Streptococcus thermophilus BT01, with a total dose of 4.5 × 1011 CFU) during dinner, while the CAS groups consumed 20 grams of casein powder 45 minutes before bed. The PRO+CAS group was given one probiotic capsule during dinner and 20 grams of casein powder 45 minutes before bed. The participants in the PLA group were given one red capsule (containing 5 grams of starch) during dinner. All participants were instructed to take the supplements only on training days, three times a week for four weeks. Additionally, isokinetic strength parameters, including absolute peak torque (APT) and average rate of force development (AvRFD), were measured for the knee extensors (ext) and flexors (flx) muscles (concentric phase at angular velocities of 60°/s and 180°/s, using the dominant leg). One-way analysis of covariance (ANCOVA) or Quade tests with a significance level of p < 0.05 was used to analyze the collected data.

The current study's findings indicated that APT-180°/s (ext) significantly increased in CAS (p = 0.008) and PRO+CAS (p = 0.003) compared to PLA. Additionally, the AvRFD-180°/s (ext) increased significantly in the PRO compared to the PLA (p = 0.007). Also, the AvRFD-60°/s (flx) increased significantly in the PRO+CAS group compared to the PLA (p = 0.014), CAS (p = 0.001), and PRO (p = 0.007). Furthermore, the AvRFD-180°/s (flx) increased significantly in the PRO+CAS compared to the CAS (p = 0.010). Moreover, the RAST average power increased dramatically in PRO+CAS compared to PLA (p = 0.003) and CAS (p = 0.02). Additionally, the Wall-squat test demonstrated a significant increase in PRO+CAS compared to PLA (p = 0.001) and PRO (p = 0.001). However, there were no significant differences in the APT-60°/s (ext&flx), APT-180°/s (flx), and AvRFD-60°/s (ext) between groups (p > 0.05).

The simultaneous consumption of casein and probiotics significantly improved anaerobic power, isokinetic strength, and lower-body muscular endurance in male soccer players. These enhancements were more pronounced than those observed with casein or probiotics alone, as supported by statistical significance and effect sizes. The findings suggest a synergistic benefit of combined supplementation for athletic performance.

Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

To investigate the impact of steam explosion on the structure of β-glucan and its regulation human gut microbiota (GM), two polysaccharides were prepared from Hericium erinaceus fruit bodies treated by steam explosion and conventional crushing, respectively. Structural analysis indicated that both two fractions were identified as β-(1 → 3)-glucan with different branching ratios attached at O-6 position. Compared with W20E obtained by conventional crushing, Q5E obtained by steam explosion possessed lower molecular weight (Mw, 2.158 × 106 g/mol) and lower branching ratio of 2:7, which influenced its effects on the diversity and metabolites of GM. W20E (Mw, 6.944 × 106 g/mol, branching ratio of 1:3) could promote n-butyrate production by increasing the abundance of Prevotellaceae_NK3B31_group, Lachnospira and Faecalibacterium. Q5E tended to improve the abundance of Lactococcus, as well as the total production of short chain fatty acids, especially for acetic and propionic acids. These findings provide reference for further development of β-glucan in healthy food.

Postoperative insulin resistance (IR) is a metabolic disorder characterized by decreased insulin sensitivity and elevated blood glucose levels following major surgery. Our previous clinical study identified a notable correlation between postoperative IR and gut microbiota, particularly butyrate-producing bacteria, yet the mechanisms remain unclear. In this study, we established gastric resection SD rat models to evaluate the impact of Clostridium butyricum NCU-27 (butyrate-producing bacteria) on postoperative IR. The results demonstrated significant reductions in fasting blood glucose (FBG), fasting insulin (FIns) levels, and HOMA-IR (6.64 ± 0.76 vs. 11.47 ± 1.32; 4.27 ± 0.59 vs. 7.40 ± 0.54) in the postoperative period compared to the control group (P < 0.05). Additionally, glucose tolerance and hepatic glycogen content were markedly improved (P < 0.001). Further exploration of butyrate demonstrated effects similar to C. butyricum NCU-27, potentially mediated through the gut-liver axis by inhibiting mTORC1 expression in liver cells, activating the IRS1/AKT pathway, enhancing glucose uptake and glycogen synthesis, suppressing gluconeogenesis, increasing insulin sensitivity, and improving IR. Finally, the use of mTORC1 agonists and inhibitors further confirmed the critical role of the mTORC1 pathway in mediating the beneficial effects of C. butyricum NCU-27 and butyrate on postoperative IR. In conclusion, this study elucidated that C. butyricum NCU-27 improves postoperative IR by regulating butyrate metabolism and inhibiting the mTORC1 pathway, offering new insights for preventing and treating post-gastrectomy IR.

Anxiety disorders are one of the major conditions in psychiatry characterized by symptoms such as worry, social and performance fears, unexpected and/or triggered panic attacks, anticipatory anxiety, and avoidance behaviors. Recent developments have drawn attention to the putative involvement of peripheral systems in the control of anxiety, and the gut microbiota has come to light as an emerging peripheral target for anxiety. The relationship between the gut-brain axis, a bidirectional communication network between the central nervous system (CNS) and enteric nervous system (ENS), and anxiety has been the subject of some recent studies. Therefore, this systematic review analyzed clinical trials evaluating the potential of microbiome modulation methods in mitigating and ameliorating anxiety disorders. Clinical studies on probiotic, prebiotic, synbiotic supplements, dietary interventions, and fecal microbiota transplantation in anxiety disorders were screened. All of the studies examined the effects of probiotic intervention. One of these studies compared a prebiotic-rich diet with probiotic supplementation. Longitudinal analyses showed that the probiotic intervention alleviated anxiety. However, most of the controlled studies reported that the probiotic intervention did not make a difference compared to placebo. Thus, the current findings suggest that it is too early to consider the promising role of microbiome modulation in the treatment of anxiety disorders. However, it is obvious that more clinical research is needed to clarify issues such as probiotic strains, prebiotic types, and their doses that may be effective on anxiety disorders.

Multiple sclerosis (MS) is defined as an inflammatory disorder that chronically affects the central nervous system of young people mostly and is distributed globally. It is associated with degeneration and demyelination of the myelin sheath around the nerves, resulting in multiple neurological disability symptoms ranging from mild to severe cases that end with paralysis sometimes. MS is one of the rising diseases globally that is unfortunately associated with reduced quality of life and adding national economic burdens. The definite MS mechanism is not clearly defined; however, all the previous researches confirm the role of the immune system as the master contributor in the pathogenesis. Innate and adaptive immune cells are activated peripherally then attracted toward the central nervous system (CNS) due to the breakdown of the blood-brain barrier. Recently, the gut-brain axis was shown to depend on gut metabolites that are produced by different microorganisms in the colon. The difference in microbiota composition between individuals is responsible for diversity in secreted metabolites that affect immune responses locally in the gut or systemically when reach blood circulation to the brain. It may enhance or suppress immune responses in the central nervous system (CNS) (repeated short forms); consequently, it may exacerbate or ameliorate MS symptoms. Recent data showed that some metabolites can be used as adjuvant therapy in MS and other inflammatory diseases. This review sheds light on the nature of MS and the possible interaction between gut microbiota and immune system regulation through the gut-brain axis, hence contributing to MS pathogenesis.

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.

Convergent data across species paint a compelling picture of the critical role of the gut and its resident microbiota in several brain functions and disorders. The chemicals mediating communication along these sophisticated highways of the brain-gut-microbiome (BGM) axis include both microbiota metabolites and classical neurotransmitters. Amongst the latter, GABA is fundamental to brain function, mediating most neuronal inhibition. Until recently, GABA's role and specific molecular targets in the periphery within the BGM axis had received limited attention. Yet, GABA is produced by neuronal and non-neuronal elements of the BGM, and recently, GABA-modulating bacteria have been identified as key players in GABAergic gut systems, indicating that GABA-mediated signalling is likely to transcend physiological boundaries and species. We review the available evidence to better understand how GABA facilitates the integration of molecularly and functionally disparate systems to bring about overall homeostasis and how GABA perturbations within the BGM axis can give rise to multi-system medical disorders, thereby magnifying the disease burden and the challenges for patient care. Analysis of transcriptomic databases revealed significant overlaps between GABAAR subunits expressed in the human brain and gut. However, in the gut, there are notable expression profiles for a select number of subunits that have received limited attention to date but could be functionally relevant for BGM axis homeostasis. GABAergic signalling, via different receptor subtypes, directly regulates BGM homeostasis by modulating the excitability of neurons within brain centres responsible for gastrointestinal (GI) function in a sex-dependent manner, potentially revealing mechanisms underlying the greater prevalence of GI disturbances in females. Apart from such top-down regulation of the BGM axis, a diverse group of cell types, including enteric neurons, glia, enteroendocrine cells, immune cells and bacteria, integrate peripheral GABA signals to influence brain functions and potentially contribute to brain disorders. We propose several priorities for this field, including the exploitation of available technologies to functionally dissect components of these GABA pathways within the BGM, with a focus on GI and brain-behaviour-disease. Furthermore, in silico ligand-receptor docking analyses using relevant bacterial metabolomic datasets, coupled with advances in knowledge of GABAAR 3D structures, could uncover new ligands with novel therapeutic potential. Finally, targeted design of dietary interventions is imperative to advancing their therapeutic potential to support GABA homeostasis across the BGM axis.

Nutritional strategies are critical for optimizing soccer players' performance and body composition. Spirulina, a protein-rich plant-based supplement, and probiotics offer individual benefits. However, their combined effects remain underexplored. This study investigated the effects of co-supplementation with spirulina and probiotics on body composition, isokinetic, isometric strength, and performance metrics in male soccer players. In a double-blind, placebo-controlled trial, forty soccer players were randomly assigned to four groups: placebo (PLA), probiotics (PRO), spirulina (SPI), and combined probiotics-spirulina (PRO + SPI). The PRO group received two probiotic capsules (a total dose of 4.5 × 1011 CFU) daily, with breakfast and dinner. The SPI group consumed two 1-g spirulina tablets twice daily (2 g total), with breakfast and dinner. The PRO + SPI group received both supplements in the same dosing regimen, while the PLA group consumed starch-based placebo capsules. Over eight weeks, participants followed identical training regimens. Pre- and post-intervention assessments included body composition (weight, BMI, fat percentage, fat weight, muscle weight), performance metrics (vertical jump, agility, speed, anaerobic sprint tests), and isokinetic and isometric knee strength tests. Statistical analyses utilized repeated measures and Bonferroni post-hoc tests. The PRO + SPI group demonstrated more significant reductions in weight (P = 0.012) and fat weight (P = 0.001) compared to the PLA group, while the SPI group showed a significant reduction in fat percentage (P = 0.034). Agility scores improved significantly in the PRO + SPI group compared to the PLA (P = 0.001) and SPI (P = 0.004) groups. Isokinetic performance metrics, including average power during knee extension at 60°/s and 180°/s, improved significantly in the PRO + SPI group compared to the PLA group (P = 0.018 and P = 0.009, respectively). Similarly, the PRO and SPI groups outperformed the PLA group in isokinetic measures such as absolute peak torque at 60°/s (P = 0.032) and 180°/s (P = 0.006). Also, maximum voluntary isometric contraction (MVIC) improved significantly in the PRO and SPI groups compared to the PLA group (P = 0.001 for both). From gut to skeletal muscle, spirulina, and probiotic co-supplementation significantly enhanced body composition, reduced weight and fat mass, and improved agility and isokinetic strength compared to placebo or individual supplementation. These results emphasize the synergistic potential of this nutritional strategy for optimizing athletic performance and recovery, warranting further investigation across diverse athletic populations.

Fermentation modifies plant polysaccharides and enhances their bioactivity. In this study, polysaccharides were extracted from Ganoderma lucidum-fermented (FBP) and non-fermented (NBP) Tartary buckwheat. The structure of the polysaccharides and their effects on gut microbial composition were explored. According to the results, the molecular weight of FBP lowered from 8.86 × 105 Da to 3.83 × 104 Da, the fermentation process produced fucose (7.72 %) and mannose (6.68 %), and the content of glucose and galactose increased. Compared with NBP, FBP showed a significant increase in solubility, crystallinity and thermal stability, while there was a decrease in apparent viscosity. The in vitro fecal fermentation results suggested that FBP promoted the production of short-chain fatty acids, with acetic acid, propionic acid and butyric acid being the main metabolites. FBP and NBP dramatically decreased the relative abundance of Escherichia-Shigella. FBP increased the relative abundances of Bacteroides, Parabacteroides, and Megamonas, while NBP increased those of Bifidobacterium and Phascolarctobacterium. Finally, further analysis of functional prediction indicated that carbohydrate metabolism, lipid metabolism and cardiovascular disease were the most vital pathways for FBP to promote health. This study offers some theoretical foundation for the chemical structure and regulation of gut microbiota by Ganoderma lucidum fermented buckwheat modified polysaccharides.

Appetite regulation is a lifestyle intervention strategy to maintain health. The regulatory effects of dietary fiber (especially insoluble dietary fiber), as a crucial element of the nutritional composition, on appetite remain poorly understood. This study investigated modulatory effects of konjac fiber (KF, with high and low expansion) and konjac powder (KP) on chyme digestion, gastrointestinal hormones, intestinal microbiota, appetite genes in hypothalamus, GLP-1 receptor (GLP-1R) protein in various tissues of rats by dietary intervention. The results showed that highly-expanded konjac fiber (HKF) significantly delayed gastric emptying and inhibited hydrolysis of chyme. Konjac fiber (KF), especially HKF, and KP increased short-chain fatty acid (SCFA) content and plasma glucagon-like peptide-1 (GLP-1) levels. HKF upregulated the expression of GLP-1R protein in rat stomachs, nucleus tractus solitaries (NTS), and area postrema (AP) of rat brain, but down-regulated the expression of appetite gene AgRP/NPY in hypothalamus, thus, inhibiting appetite, reducing daily food intake and weight gain. Overall, this study reveals the mechanism through which expandable konjac fiber modulates appetite and chyme digestion in vivo by stomach-intestine-brain axis. Our findings provide an insight into the regulatory effects of insoluble dietary fiber on appetite and offered a valuable reference for the development of satiety-enhancing functional foods.

The gut-brain axis (GBA) is a bidirectional communication network between the gastrointestinal tract and the brain, modulated by gut microbiota and related biomarkers. Malnutrition disrupts GBA homeostasis, exacerbating GBA dysfunction through gut dysbiosis, impaired neuroactive metabolite production, and systemic inflammation. Nutraceuticals, including probiotics, prebiotics, synbiotics, postbiotics, and paraprobiotics, offer a promising approach to improving GBA homeostasis by modulating the gut microbiota composition and related neuroactive metabolites. This review aims to elucidate the interplay between gut microbiota-derived biomarkers and GBA dysfunction in malnutrition and evaluate the potential of nutraceuticals in combating malnutrition. Furthermore, it explores the future of personalised nutraceutical interventions tailored to individual genetic and microbiome profiles, providing a targeted approach to optimise health outcomes. The integration of nutraceuticals into GBA health management could transform malnutrition treatment and improve cognitive and metabolic health.

The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.

In recent years, the gut microbiota and derived metabolites have emerged as relevant players in modulating several brain functions, including energy balance control1-3. This form of distant communication mirrors that of metabolic hormones (for example, leptin, ghrelin), which convey information about the organism's energy status by exerting effects on diverse brain regions, including the master homeostatic centre, the hypothalamus4. However, whether the hypothalamus is also able to influence gut microbiota composition remains enigmatic. Here we present a study designed to unravel this challenging question. To this aim, we used chemogenetics5 (to selectively activate or inhibit hypothalamic pro-opiomelanocortin or agouti-related peptide neurons) or centrally administered leptin or ghrelin to male mice. Subsequently, we conducted microbiota composition analysis throughout the gut using 16S rRNA gene sequencing. Our results showed that these brain interventions significantly changed the gut microbiota in an anatomical and short-term (2-4 h) fashion. Transcriptomic analysis indicated that these changes were associated with the reconfiguration of neuronal and synaptic pathways in the duodenum concomitant with increased sympathetic tone. Interestingly, diet-induced obesity attenuated the brain-mediated changes triggered by leptin in gut microbiota communities and sympathetic activation. Our findings reveal a previously unanticipated brain-gut axis that acutely attunes microbiota composition on fast timescales, with potential implications for meal-to-meal adjustments and systemic energy balance control.

Overabundance of reactive oxygen species (oxidative distress) leads to redox homeostasis disturbance and is associated with many pathological conditions. Accumulating evidence suggests that oxidative distress may contribute to osteoporosis. This review thoroughly outlines the relationships among osteoporosis, redox homeostasis, and alcohol addiction, since these relations are not sufficiently known and subsequently summarized. The brain-bone axis plays a crucial role in alcohol-induced damage to the nervous and skeletal systems. Alterations in the nervous system can lead to osteoporosis because the central nervous system is involved in bone remodeling through various neural pathways. Conversely, as an endocrine organ, bone secretes a number of bone-derived factors (osteokines), which can influence brain function and behavior. As a result, osteoporosis is more common in individuals with neurological disorders, and sudden neurological events can rapidly increase the risk of osteoporosis. Excessive alcohol consumption is linked to many neurological complications, as well as osteoporosis, which are manifested by disrupted redox homeostasis, inflammation, neurodegeneration, inhibition of neurogenesis, decreased bone mineral density, impaired bone microarchitecture, altered mineral homeostasis, raising fracture risk, hormonal dysregulation, and altered gut microbiota composition. Compared to men, alcohol dependence has more negative consequences for women, including an increased risk of liver, cardiovascular, metabolic, mental disorders, and breast cancer. Abstinence has been demonstrated to improve bone and brain health in alcohol addiction. The discovery of the brain-bone axis may lead to the development of new therapeutic approaches for alcohol and other substance addictions. Further research is needed in this direction, as many questions remain unanswered.

The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.

Lacto-fermented fruits and vegetables (FVs) such as kimchi, sauerkraut, and fermented olives and nonalcoholic juices have a long history as dietary staples. Herein, the production steps and microbial ecology of lacto-fermented FVs are discussed alongside findings from human and laboratory studies investigating the health benefits of these foods. Lacto-fermented FVs are enriched in beneficial live microbes and bioactive compounds, including lactic and acetic acids, phenolic compounds, bacteriocins, and amino acid derivatives such as indole-3-lactic acid, phenyl-lactic acid, and γ-aminobutyric acid. At least 11 human studies have been performed on kimchi, whereas others have been investigated in only one or two trials. Besides exploring the health benefits, it is imperative to ensure that these foods made either commercially or at home have minimal risk for foodborne illness and exposure to undesired compounds like biogenic amines. Development of starter-culture strains and production protocols can lead to lacto-fermented FVs designed for specific health benefits.

This study investigated the effects of the polyphenol-polysaccharide complex (HPC) and its purified components (PC1 and PC4), obtained from Hizikia fusiforme, on the human gut microbiota during in vitro simulated digestion and fecal fermentation. Results showed a gradual increase in reducing sugar content for HPC, PC1, and PC4 during simulated digestion, accompanied by a slight decrease in molecular weight, indicating that these complexes were not completely digested during oral-gastrointestinal digestion. However, following fermentation, the molecular weights of HPC, PC1, and PC4 decreased significantly, and the molar ratios of monosaccharide compositions changed considerably compared with prefermentation values. Thus, these complexes were degraded and used by the intestinal microbiota to produce short-chain fatty acids, which decreased the pH. In addition, after fecal fermentation, beneficial bacteria such as Bacteroides, Parabacteroides, and Bifidobacterium became more abundant, whereas the amount of harmful bacteria such as Fusobacterium and Escherichia/Shigella decreased, revealing the regulation by the complex on the intestinal microbiota. In conclusion, the polyphenol-polysaccharide complex improves the composition and abundance of the human gastrointestinal microbiota, thereby supporting gut health.

Replacing sugar with non-nutritive sweeteners (NNS) is a common dietary strategy for reducing the caloric content and glycemic index of foods and beverages. However, the efficacy of this strategy in preventing and managing metabolic syndrome and its associated comorbidities remains uncertain. Human cohort studies suggest that NNS contribute to, rather than prevent, metabolic syndrome, whereas randomized controlled trials yield heterogeneous outcomes, ranging from beneficial to detrimental impacts on cardiometabolic health. The World Health Organization recently issued a conditional recommendation against using NNS, citing the need for additional evidence causally linking sweeteners to health effects. One proposed mechanism through which NNS induce metabolic derangements is through disruption of the gut microbiome, a link strongly supported by evidence in preclinical models. This review summarizes the evidence for similar effects in interventional and observational trials in humans. The limited available data highlight heterogeneity between trials, as some, but not all, find NNS consumption associated with microbiome modulation as well as metabolic effects independent of sweetener type. In other trials, the lack of microbiome changes coincides with the absence of metabolic effects. We discuss the hypothesis that the impacts of NNS on health are personalized and microbiome dependent. Thus, a precision nutrition approach may help resolve the conflicting reports regarding NNS impacts on the microbiome and health. This review also discusses additional factors contributing to study heterogeneity that should be addressed in future clinical trials to clarify the relationship between NNS, the microbiome, and health to better inform dietary guidelines and public health policies.

The microbiota-gut-brain axis has been proposed as a potential modulator of mood disorders such as major depression. Complex bidirectional biochemical activities in this axis have been posited to participate in adverse mood disorders. Environmental and genetic factors have dominated recent discussions on depression. The prescription of antibiotics, antidepressants, adverse negative DNA methylation reactions and a dysbiotic gut microbiome have been cited as causal for the development and progression of depression. While research continues to investigate the microbiome-gut-brain axis, this review will explore the state of persistence of gut bacteria that underpins bacterial dormancy, possibly due to adverse environmental conditions and/or pharmaceutical prescriptions. Bacterial dormancy persistence in the intestinal microbial cohort could affect the role of bacterial epigenomes and DNA methylations. DNA methylations are highly motif driven exerting significant control on bacterial phenotypes that can disrupt bacterial metabolism and neurotransmitter formation in the gut, outcomes that can support adverse mood dispositions.

The microbiota-gut-brain-axis (MGBA) plays a role in the aetiology of mental disorders. Depression, a leading cause of disability worldwide, may be improved by probiotics. The aim of this narrative review is to investigate and synthesize the current evidence linking probiotic food supplementation with depressive symptomology.

The gut and the brain communicate and interact via the MGBA through inflammation and the immune system, short chain fatty acid production, neuronal innervation and activation as well as endocrine and neurotransmitter modulation. Dysregulation of gut-brain pathways are caused by gut dysbiosis and implicated in the onset, persistence and exacerbation of depression related symptoms. Modulation of the gut microbiota via administration of probiotics has shown to reduce depressive symptom severity with Bifidobacterium and Lactobacillus strains being the most reported. Probiotics may produce greater benefits in mild depression rather than in chronic, treatment resistant depression. Probiotic supplementation is a promising and safe approach for the prevention of severe depressive disorders in high-risk individuals such as people with subthreshold depression. However, the mechanistic pathways of the MGBA require further investigation and additional human clinical trials are necessary to evaluate the role of probiotics on depression.

Polysaccharides, vital biological macromolecules ubiquitous in organisms, have garnered attention as potential therapeutic candidates for ulcerative colitis (UC). However, the therapeutic potential of Rhodiola crenulata polysaccharides (RCP) in UC remains largely unexplored. The RCP was prepared by boiling water extraction, 80% alcohol precipitation, membrane separation, and D101 macroporous resin purification. The monosaccharide composition of RCP (Mw = 67.848 kDa) includes mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with a molar ratio of 0.22:1:0.07:7.03:2.88:0.64:4.12. In vivo experiments have shown that RCP can improve DSS induced weight loss in UC mice, decrease disease activity index (DAI), alleviate histopathological changes in colon tissue, and suppress the levels of pro-inflammatory cytokine IL-6 and MPO activity. Immunohistochemical results showed that essential tight junction proteins such as occludin, claudin1, and ZO-1 were upregulated, improving the integrity of the intestinal barrier. Importantly, RCP regulated the abundance of the intestinal microbiota by reducing the Firmicutes-to-Bacteroidetes ratio (F/B), increasing beneficial bacteria such as Muribaculaceae and Bifidobacterium, decreasing harmful bacteria including Erysipelotrichaceae, Faecalibaculum, Lachnospiraceae_unclassified, Parabacteroides, and Ruminiclostridium_9. Additionally, it enhanced the restoration of acetic acid, propionic acid, isovaleric acid, and valeric acid to maintain intestinal SCFA levels, thereby restoring the intestinal microecology. Therefore, RCP has excellent therapeutic effects on UC and is worthy of further drug development and clinical treatment.

Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes (13C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with 13C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.

Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.

Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and gamma-aminobutyric acid (GABA), act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription. In addition, we found that CXC chemokine ligand 12 (CXCL12) produced from Foxl1high sub-epithelial mesenchymal cells induces epithelial cell cycle arrest through modulation of the mevalonate-cholesterol synthesis pathway, which suppresses tumor progression in ApcMin/+ mice. We identified that Foxl1high sub-epithelial cells highly express CXCL12 among colonic mesenchymal cells. Foxl1-cre; Cxcl12f/f mice showed an increased number of Ki67+ colonic epithelial cells. CXCL12-induced Ca2+ mobilization facilitated phosphorylation of AMPK in intestinal epithelial cells, which inhibits the maturation of sterol regulatory element-binding proteins (SREBPs) that are responsible for mevalonate pathway activation. Furthermore, Cxcl12 deficiency in Foxl1-expressing cells promoted tumor development in the small and large intestines of ApcMin/+ mice. Collectively, these results demonstrate that CXCL12 secreted from Foxl1high mesenchymal cells manipulates intestinal epithelial cell metabolism, which links to the prevention of tumor progression in ApcMin/+ mice.

Successfully adapting to a feral lifestyle with different access to food, shelter and other resources requires rapid physiological and behavioural changes, which could potentially be facilitated by gut microbiota plasticity. To investigate whether alterations in gut microbiota support this transition to a feral lifestyle, we analysed the gut microbiomes of domestic and feral cats from six geographically diverse locations using genome-resolved metagenomics. By reconstructing 229 non-redundant metagenome-assembled genomes from 92 cats, we identified a typical carnivore microbiome structure, with notable diversity and taxonomic differences across regions. While overall diversity metrics did not differ significantly between domestic and feral cats, hierarchical modelling of species communities, accounting for geographic and sex covariates, revealed significantly larger microbial functional capacities among feral cats. The increased capacity for amino acid and lipid degradation corresponds to feral cats' dietary reliance on crude protein and fat. A second modelling analysis, using behavioural phenotype as the main predictor, unveiled a positive association between microbial production of short-chain fatty acids, neurotransmitters and vitamins and cat aggressiveness, suggesting that gut microbes might contribute to heightened aggression and elusiveness observed in feral cats. Functional microbiome shifts may therefore play a significant role in the development of physiological and behavioural traits advantageous for a feral lifestyle, a hypothesis that warrants validation through microbiota manipulation experiments.

The human gut flora of trillions of bacteria is vital for general health and greatly influences digestion, immune system function, and brain development. Through neuronal, hormonal, and immunological channels, the gut-brain axis (GBA), a bidirectional communication network, links the gut microbiota to the central nervous system (CNS). This relationship has been linked to affective diseases, including depression and anxiety, as well as mental health issues. This review explores the intricate relationship between gut bacteria and mood disorders, focusing on how gut microbiota-host interactions, immune system modulation, and neurotransmitter control support mental health. The function of important microbial metabolites, including short-chain fatty acids (SCFAs), in preserving blood-brain barrier integrity and modulating neuroinflammation is covered in this review. It also examines the bidirectional impact between gut health and mental health, including how dysbiosis could aggravate mood disorders and how depressed states might change the composition of gut bacteria. Furthermore, we discuss how psychotropic drugs affect gut flora and consider other elements such as nutrition and lifestyle that affect gut microbiome composition. Potential paths for treating mood disorders through gut microbiota modification are presented as emerging treatment techniques, including probiotics, nutritional therapies, and precision medicine. The development of new therapeutic approaches for mood disorders depends on the awareness of the GBA. Gut bacteria significantly affect mental health through immune modulation, neurotransmitter generation, and other intricate processes. Future studies should concentrate on large, varied populations to better understand these interactions and to create customized treatments that combine gut microbiota modulation with conventional mental health therapies.

Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.

Once considered to have only local influences on the gut mucosa, short-chain fatty acids (SCFAs) now appear to have a much wider anti-inflammatory, immune-modulating, systemic effect. This article reviews recent evidence to suggest a much wider clinical application of this valued dietary substrate.

SCFAs act systemically through stimulation of G protein receptors (GPRs) and inhibition of histone deacetylases (HDACs). SCFAs cause appetite suppression, reduce systemic inflammation, improve insulin sensitivity, increase energy expenditure, promote mitochondrial function, stimulate satiety, reduce blood pressure, and improve cognitive function from various neurologic maladies.

Dietary strategies should be implemented to provide this beneficial substrate across a wide spectrum of disease conditions. Use of prebiotic fiber or liquid supplements containing high SCFA-producing organisms should be considered as therapeutic targets for multiple metabolic, immunologic, and neurodegenerative diseases.

Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.

Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, the underlying mechanisms remain unclear. To address this, we investigated the impact of butyrate on energy metabolism in mouse brain slices, primary cultures of astrocytes and neurons and in-vivo by dynamic isotope labelling with [U-13C]butyrate and [1,2-13C]acetate to map metabolism via mass spectrometry. Metabolic competition assays in cerebral cortical slices revealed no competition between butyrate and the ketone body, β-hydroxybutyrate, but competition with acetate. Astrocytes favoured butyrate metabolism compared to neurons, suggesting that the astrocytic compartment is the primary site of butyrate metabolism. In-vivo metabolism investigated in the 5xFAD mouse, an AD pathology model, showed no difference in 13C-labelling of TCA cycle metabolites between wild-type and 5xFAD brains, but butyrate metabolism remained elevated compared to acetate in both groups, indicating sustained uptake and metabolism in 5xFAD mice. Overall, these findings highlight the role of astrocytes in butyrate metabolism and the potential use of butyrate as an alternative brain fuel source.

The gut microbiome, comprising bacteria, viruses, fungi, and bacteriophages, is one of the largest microbial ecosystems in the human body and plays a crucial role in various physiological processes. This review explores the interaction between the gut microbiome and enteroendocrine cells (EECs), specialized hormone-secreting cells within the intestinal epithelium. EECs, which constitute less than 1% of intestinal epithelial cells, are key regulators of gut-brain communication, energy metabolism, gut motility, and satiety. Recent evidence shows that gut microbiota directly influence EEC function, maturation, and hormone secretion. For instance, commensal bacteria regulate the production of hormones like glucagon-like peptide 1 and peptide YY by modulating gene expression and vesicle cycling in EE cells. Additionally, metabolites such as short-chain fatty acids, derived from microbial fermentation, play a central role in regulating EEC signaling pathways that affect metabolism, gut motility, and immune responses. Furthermore, the interplay between gut microbiota, EECs, and metabolic diseases, such as obesity and diabetes, is examined, emphasizing the microbiome's dual role in promoting health and contributing to disease states. This intricate relationship between the gut microbiome and EECs offers new insights into potential therapeutic strategies for metabolic and gut disorders.

The vagus nerve is proposed to enable communication between the gut microbiome and the brain, but activity-based evidence is lacking. We find that mice reared germ-free exhibit decreased vagal tone relative to colonized controls, which is reversed via microbiota restoration. Perfusing antibiotics into the small intestines of conventional mice, but not germ-free mice, acutely decreases vagal activity which is restored upon re-perfusion with intestinal filtrates from conventional, but not germ-free, mice. Microbiome-dependent short-chain fatty acids, bile acids, and 3-indoxyl sulfate indirectly stimulate vagal activity in a receptor-dependent manner. Serial perfusion of each metabolite class activates both shared and distinct neuronal subsets with varied response kinetics. Metabolite-induced and receptor-dependent increases in vagal activity correspond with the activation of brainstem neurons. Results from this study reveal that the gut microbiome regulates select metabolites in the intestinal lumen that differentially activate vagal afferent neurons, thereby enabling the microbial modulation of chemosensory signals for gut-brain communication.

Dietary fiber can suppress excess adipose tissue and weight gain in rodents and humans when fed high fat diets. The gut microbiome is thought to have a key role, although exactly how remains unclear. In a tightly controlled murine study, we explored how different types of dietary fiber and doses affect the gut microbiota and gut epithelial gene expression. We show that 10% pectin and 10% FOS suppress high fat diet (HFD)-induced weight gain, effects not seen at 2% doses. Furthermore, 2 and 10% mixtures of dietary fiber were also without effect. Each fiber treatment stimulated a distinct gut microbiota profile at the family and operational taxonomic unit (OTU) level. Mechanistically it is likely that the single 10% fiber dose shifted selected bacteria above some threshold abundance, required to suppress body weight, which was not achieved by the 10% Mix, composed of 4 fibers each at 2.5%. Plasma levels of the gut hormone PYY were elevated by 10% pectin and FOS, but not 10% mixed fibers, and similarly RNA seq revealed some distinct effects of the 10% single fibers on gut epithelial gene expression. These data show how the ability of dietary fiber to suppress HFD-induced weight gain is dependent upon both fiber type and dose. It also shows that the microbial response to dietary fiber is distinct and that there is not a single microbial response associated with the inhibition of adiposity and weight gain. PYY seems key to the latter response, although the role of other factors such as Reg3γ and CCK needs to be explored.

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.

Obesity is a risk factor for non-communicable diseases such as cardiovascular disease and diabetes, which are leading causes of death and disability. Today, China has the largest number of overweight and obese people, imposing a heavy burden on China's healthcare system. Obesity adversely affects the central nervous system (CNS), especially cognitive functions such as executive power, working memory, learning, and so on. The gradual increase in adult obesity rates has been accompanied by a increase in childhood obesity rates. In the past two decades, the obesity rate among children under 5 years of age has increased from 32 to 42 million. If childhood obesity is not intervened in the early years, it will continue into adulthood and remain there for life. Among the potential causative factors, early lifestyle may influence the composition of the gut flora in childhood obesity, such as the rate and intake of high-energy foods, low levels of physical activity, may persist into adulthood, thus, early lifestyle interventions may improve the composition of the gut flora in obese children. Adipose Axis plays an important role in the development of obesity. Adipose tissue is characterized by increased expression of nucleoside diphosphate-linked molecule X-type motif 2 (NUDT2), amphiphilic protein AMPH genes, which encode proteins that all play important roles in the CNS. NUDT2 is associated with intellectual disability. Furthermore, amphiphysin (AMPH) is involved in glutamatergic signaling, ganglionic synapse development, and maturation, which is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). All of the above studies show that obesity is closely related to cognitive decline in patients. Animal experiments have confirmed that obesity causes changes in cognitive function. For example, high-fat diets rich in long- and medium-chain saturated fatty acids may adversely affect cognitive function in obese mice. This process may be attributed to the Short-Chain Fatty Acid (SCFA)-rich high-fat diet (HFD) activating enterocyte TLR signaling, especially TLR-2 and TLR-4, altering the downstream MyD88-4 signaling, thereby impacting the downstream MyD88-NF-κB signaling cascade and up-regulating the levels of pro-inflammatory factors and lipopolysaccharide (LPS). These changes result in the loss of integrity of the intestinal mucosa and cause an imbalance in the internal environment. Obesity may lead to the disruption of the intestinal flora and damage the intestinal barrier function, causing intestinal flora dysbiosis. In recent years, a growing number of studies have investigated the relationship between obesity and the intestinal flora. For example, high-fat and high-sugar diets have been found to lead to the thinning of the mucus layer of the colon, a decrease in the number of tight junction proteins, and an increase in intestinal permeability in mice. Such changes alter the composition of intestinal microorganisms, allow endotoxins into the blood circulation, and induce neuroinflammation and brain damage. Therefore, obesity affects cognitive function and is even hereditary. This paper reviews the obesity-induced cognitive dysfunction, the underlying mechanisms, the research progress of intestinal flora dysregulation in obese patients, the relationship between intestinal flora and cognitive function changes, and the research progress on intestinal flora dysregulation in obese patients. We want to regulate the internal environment of obese patients from the perspective of intestinal flora, improving the cognitive function of obese patients, and prevent obesity-induced changes in related neurological functions.

Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson's disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson's disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease's progression through the bidirectional transmission of inflammatory signals along the gut-brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson's disease, thereby paving the way for novel avenues in the research and treatment of this condition.

Metabolic syndrome (MS) refers to a cluster of metabolic disorders characterized by systemic chronic inflammation. Er Miao San (EMS) is a classic traditional Chinese medicine compound containing Phellodendron amurense and Atractylodis rhizome at a ratio of 1:1, proven to be effective against inflammatory diseases in clinical practice. Nevertheless, the precise functions of EMS in treating MS and its underlying mechanism have yet to be elucidated.

This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (HHSF)-induced MS in pigs.

Blood biochemical indices and metabolome analysis were employed to confirm the successful establishment of the MS model, and the preliminary evaluation of the intervention effect of EMS was conducted. Subsequently, a parallel microbiota analysis of the tongue and cecum was combined with metabolomic analysis, histopathologic examination, and other molecular biological detection to further assess the administration mechanism of EMS.

The results demonstrated that EMS significantly reduced the excessive weight gain rate, fat accumulation, hyperlipidemia, hyperglycemia, and systemic inflammation while improving serum metabolic disorder in MS pigs. Moreover, microbiota analysis indicates that EMS restored the diversity and composition of oral-gut microbiota by increasing the proportions of Lactobacillus (gut), Roseburia (gut), Faecalibacterium (gut), CF231 (gut), Streptococcus (gut), Prevotella (gut), while decreasing those of Chryseobacterium (oral), Corynebacterium (oral), Clostridium (oral), Oscillospira (gut), and Turicibacter (oral, gut). Subsequently, EMS up-regulated the concentrations of acetic acid, butyric acid, propionic acid, while down-regulated isobutyric acid and isovaleric acid. This resulted in a suppression of HDAC3 expression and an increase of SCL16A1 expression in the colon. Notably, the changes in acetic acid and butyric acid showed a strong correlation with gut microbiota. Additionally, EMS reduced the serum level of lipopolysaccharide (LPS) and enhanced epithelial barrier integrity by inhibiting the LPS-TLR4/MyD88/NF-κB pathways.

EMS was found to ameliorate MS by alleviating the dysbiosis of the oral-gut microbiota and serum metabolome, thereby improving gut barrier and reducing systemic inflammation. These findings suggest that EMS holds promise as a therapeutic agent for MS.

Nicotine, a neuroactive substance in tobacco products, has been widely studied for its effects on feeding and body weight, mostly focusing on the involvement of nervous system, metabolism, hormones, and gut microbiota. To elucidate the action mechanism of nicotine on feeding and body weight, especially the underlying neurobiological mechanisms, we reviewed the studies on nicotine's effects on feeding and body weight by the regulation of various nerve systems, energy expenditure, peripheral hormones, gut microbiota, etc. The role of neuronal signaling molecules such as AMP-activated protein kinase (AMPK) and kappa opioid receptor (κOR) were specialized in the nicotine-regulating energy expenditure. The energy homeostasis-related neurons, pro-opiomelanocortin (POMC), agouti-related peptide (AgRP), prolactin-releasing hormone (Prlh), etc, were discussed about the responsibility for nicotine's effects on feeding. Nicotine's actions on hypothalamus and its related neural circuits were described in view of peripheral nervous system, reward system, adipose browning, hormone secretion, and gut-brain axis. Elucidation of neurobiological mechanism of nicotine's actions on feeding and body weight will be of immense value to the therapeutic strategies of smoking, and advance the medicine research for the therapy of obesity.