Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease) is a chronic liver disease affecting over a billion individuals worldwide. MASLD can gradually develop into more severe liver pathologies, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and liver malignancy. Notably, although being a global health problem, there are very limited therapeutic options against MASLD and its related diseases. While a thyroid hormone receptor agonist (resmetirom) is recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in MASLD and MASH incidence, it is urgent to develop novel and effective therapeutic strategies against these prevalent liver diseases. In this article, the pathogenic mechanisms of MASLD and MASH, including insulin resistance, dysregulated nuclear receptor signaling, and genetic risk factors (eg, patatin-like phospholipase domain-containing 3 and hydroxysteroid 17-β dehydrogenase-13), are introduced. Various therapeutic interventions against MASH are then explored, including approved medication (resmetirom), drugs that are currently in clinical trials (eg, glucagon-like peptide 1 receptor agonist, fibroblast growth factor 21 analog, and PPAR agonist), and those failed in previous trials (eg, obeticholic acid and stearoyl-CoA desaturase 1 antagonist). Moreover, given that the role of gut microbes in MASLD is increasingly acknowledged, alterations in the gut microbiota and microbial mechanisms in MASLD development are elucidated. Therapeutic approaches that target the gut microbiota (eg, dietary intervention and probiotics) against MASLD and related diseases are further explored. With better understanding of the multifaceted pathogenic mechanisms, the development of innovative therapeutics that target the root causes of MASLD and MASH is greatly facilitated. The possibility of alleviating MASH and achieving better patient outcomes is within reach. SIGNIFICANCE STATEMENT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, and it can progress to more severe pathologies, including steatohepatitis, cirrhosis, and liver cancer. Better understanding of the pathogenic mechanisms of these diseases has facilitated the development of innovative therapeutic strategies. Moreover, increasing evidence has illustrated the crucial role of gut microbiota in the pathogenesis of MASLD and related diseases. It may be clinically feasible to target gut microbes to alleviate MASLD in the future.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver transplantation, as well as a significant risk factor for cardiovascular disease and mortality. Due to the ever-increasing number of patients, the long-term asymptomatic course of the disease, serious complications, and lack of preventive programs, as well as insufficient awareness of the disease among patients and doctors themselves, MASLD is a growing interdisciplinary problem and a real challenge for modern medicine. The main cause of MASLD is an inappropriate lifestyle-inadequate nutrition and insufficient physical activity, which lead to various components of metabolic syndrome. Lifestyle changes-appropriate diet, weight reduction, and systematic physical activity-are also the basis for the prevention and treatment of MASLD. Hence, in recent years, so much importance has been attached to lifestyle medicine, to non-pharmacological treatment as prevention of lifestyle diseases. The narrative review presents possible therapeutic options for non-pharmacological management in the prevention and treatment of MASLD. The best documented and available diets used in MASLD were discussed, focusing on the benefits and drawbacks of the Mediterranean, high-protein, ketogenic, and intermittent fasting diets. In addition, the most recent recommendations regarding physical activity are summarized.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common multi-factorial liver disease, and its incidence is gradually increasing worldwide. Many reports have revealed that intestinal flora plays a crucial role for the occurrence and development of MASLD, through mechanisms such as flora translocation, endogenous ethanol production, dysregulation of choline metabolism and bile acid, and endotoxemia. Here, we review the relationship between intestinal flora and MASLD, as well as interventions for MASLD, such as prebiotics, probiotics, synbiotics, and intestinal flora transplantation. Intervention strategies targeting the intestinal flora along with its metabolites may be new targets for preventing and treating MASLD.

The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.

A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.

A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].

The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.

https://www.crd.york.ac.uk/prospero/, CRD42023450093.

Increasing prevalence of childhood obesity has emerged as a critical global public health concern. Recent studies have challenged the previous belief that obesity was solely a result of excessive caloric intake. Alterations in early-life gut microbiota can contribute to childhood obesity through their influence on nutrient absorption and metabolism, initiation of inflammatory responses, and regulation of gut-brain communication. The gut microbiota is increasingly acknowledged to play a crucial role in human health, as certain beneficial bacteria have been scientifically proven to possess the capacity to reduce body fat content and enhance intestinal barrier function and their metabolic products to exhibit anti-inflammatory effect. Examples of such microbes include bifidobacteria, Akkermansia muciniphila, and Lactobacillus reuteri. In contrast, an increase in Enterobacteriaceae and propionate-producing bacteria (Prevotellaceae and Veillonellaceae) has been implicated in the induction of low-grade systemic inflammation and disturbances in lipid metabolism, which can predispose individuals to obesity. Studies have demonstrated that modulating the gut microbiota through diet, lifestyle changes, prebiotics, probiotics, or fecal microbiota transplantation may contribute to gut homeostasis and the management of obesity and its associated comorbidities. This review aimed to elucidate the impact of alterations in gut microbiota composition during early life on childhood obesity and explores the mechanisms by which gut microbiota contributes to the pathogenesis of obesity and specifically focused on recent advances in using short-chain fatty acids for regulating gut microbiota and ameliorating obesity. Additionally, it aimed to discuss the therapeutic strategies for childhood obesity from the perspective of gut microbiota, aiming to provide a theoretical foundation for interventions targeting pediatric obesity based on gut microbiota.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a prevalent hepatic condition linked to metabolic alterations. It gradually causes liver damage and potentially progresses to cirrhosis. Despite its significance, research, especially in the pediatric population, is limited, leading to contradictory findings in diagnosis and treatment. This meta-analysis aims to synthesize existing literature on therapeutic interventions for MASLD in children and adolescents.

A comprehensive search of randomized controlled clinical trials yielded 634 entries from PubMed, Scopus, and Web of Science up to 2023. Interventions included medications, behavioral modifications, dietary changes, probiotics, supplements, surgical procedures, or combinations. The analysis focused on studies with treatment duration of at least 3 months, employing a random-effects REML meta-analysis model. Treatment effects on anthropometric measurements and biochemical components were examined and adjusted for heterogeneity factors analysis. A bibliometric analysis for insights into research contributors was performed.

The systematic review incorporated 31 clinical trials, with 24 meeting criteria for meta-analysis. These comprised 3 medication studies, 20 with supplements, 4 focusing on lifestyle, and 4 centered on diets. Significant overall treatment effects were observed for ALT, AST, BMI, and HOMA-IR mainly by supplements and lifestyle. Meta-regression identified age, BMI changes, and treatment duration as factors modifying ALT concentrations. Bibliometric analysis involving 31 linked studies highlighted contributions from 13 countries, with the USA, Spain, and Chile being the most influential.

We conclude that supplementation and lifestyle changes can effectively impact ALT and AST levels, which can help address liver issues in obese children. However, the evaluation of risk bias, the high heterogeneity, and the bibliometric analysis emphasize the need for more high-quality studies and broader inclusion of diverse child populations to provide better therapeutic recommendations.

PROSPERO, CRD42023393952. Registered on January 25, 2023.

Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely "dysbiosis", has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the "gut-liver axis". Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.

With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.

One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.

Liver diseases are among the most commonly diagnosed conditions, with the main risk factors being inappropriate lifestyles, including poor diet, excessive alcohol consumption, low physical activity and smoking, including electronic cigarettes. Non-communicable chronic liver diseases also often develop as a result of accompanying overweight and obesity, as well as type 2 diabetes.

The literature on risk factors for non-communicable chronic liver diseases, which show a high strong influence on their occurrence, was analysed.

Measures to prevent non-communicable chronic liver disease include the selection of suitable food ingredients that have proven protective effects on the liver. Such ingredients include dietary fibre, probiotics, herbs, various types of polyphenols and fatty acids (omega-3).

Because of their liver-protective effects, nutritionists recommend consuming vegetables, fruits, herbs and spices that provide valuable ingredients with anti-inflammatory and anti-cancer effects. These components should be provided with food and, in the case of probiotics, supplementation appears to be important. As a preventive measure, a diet rich in these nutrients is therefore recommended, as well as one that prevents overweight and other diseases that can result in liver disease.

The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.

Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of Lactiplantibacillus plantarum SG5 (formerly known as Lactobacillus plantarum, abbreviated as L. plantarum) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of L. plantarum SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that L. plantarum SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9-39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of L. plantarum SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.

Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.

This review provides a comprehensive overview of the current state of probiotic research, covering a wide range of topics, including strain identification, functional characterization, preclinical and clinical evaluations, mechanisms of action, therapeutic applications, manufacturing considerations, and future directions. The screening process for potential probiotics involves phenotypic and genomic analysis to identify strains with health-promoting properties while excluding those with any factor that could be harmful to the host. In vitro assays for evaluating probiotic traits such as acid tolerance, bile metabolism, adhesion properties, and antimicrobial effects are described. The review highlights promising findings from in vivo studies on probiotic mitigation of inflammatory bowel diseases, chemotherapy-induced mucositis, dysbiosis, obesity, diabetes, and bone health, primarily through immunomodulation and modulation of the local microbiota in human and animal models. Clinical studies demonstrating beneficial modulation of metabolic diseases and human central nervous system function are also presented. Manufacturing processes significantly impact the growth, viability, and properties of probiotics, and the composition of the product matrix and supplementation with prebiotics or other strains can modify their effects. The lack of regulatory oversight raises concerns about the quality, safety, and labeling accuracy of commercial probiotics, particularly for vulnerable populations. Advancements in multi-omics approaches, especially probiogenomics, will provide a deeper understanding of the mechanisms behind probiotic functionality, allowing for personalized and targeted probiotic therapies. However, it is crucial to simultaneously focus on improving manufacturing practices, implementing quality control standards, and establishing regulatory oversight to ensure the safety and efficacy of probiotic products in the face of increasing therapeutic applications.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator‑activated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.

Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.

The efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) -2.13 kg/m2, 95% credible interval (CrI) [-2.7, -1.57]), waist circumference (MD -1.34 cm, 95% CrI [-2.33, -0.35]), total cholesterol (MD -6.55 mg/dL, 95% CrI [-10.61, -2.45]), triglycerides (MD -3.71 mg/dL, 95% CrI [-5.76, -1.67]), leptin (MD -3.99 ng/mL, 95% CrI [-4.68, -3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD -1.21 mg/L, 95% CrI [-1.45, -0.97]). Synbiotics were effective in reducing BMI-z score (MD -0.07, 95% CrI [-0.10, -0.04]) and LDL-C (MD -1.54 mg/dL, 95% CrI [-1.98, -1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach. More specifically, studies on diet alone have focused on the possible role of carbohydrate or fat restriction, albeit without a definite answer on the best approach. Weight loss after dietary intervention in children with obesity and MASLD has a beneficial effect, regardless of the diet used. In relation to the role of exercise in MASLD reversal, indirect evidence comes from studies showing that a sedentary lifestyle leading to poor fitness, and low muscle mass is associated with MASLD. However, research on the direct effect of exercise on MASLD in children is scarce. A combination of diet and exercise seems to be beneficial with several studies showing improvement in surrogate markers of MASLD, such as serum alanine aminotransferase and hepatic fat fraction, the latter evaluated with imaging studies. Several dietary supplements, such as vitamin E, probiotics, and omega-3 fatty acid supplements have also been studied in children and adolescents with MASLD, but with equivocal results. This review aims to critically present available data on the effects of lifestyle interventions, including diet, exercise, and dietary supplements, on pediatric MASLD, thus suggesting a frame for future research that could enhance our knowledge on pediatric MASLD management and optimize clinicians' approach to this vexing medical condition.

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.

There is a contradiction in the use of microbiota-therapies, including probiotics, prebiotics, and synbiotics, to improve the condition of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this review was to evaluate the effect of microbiota-therapy on liver injury, inflammation, and lipid levels in individuals with NAFLD.

Using Pubmed, Embase, Cochrane Library, and Web of Science databases were searched for articles on the use of prebiotic, probiotic, or synbiotic for the treatment of patients with NAFLD up to March 2024.

Thirty-four studies involving 12,682 individuals were included. Meta-analysis indicated that probiotic, prebiotic, and synbiotic supplementation significantly improved liver injury (hepatic fibrosis, SMD = -0.31; 95% CI: -0.53, -0.09; aspartate aminotransferase, SMD = -0.35; 95% CI: -0.55, -0.15; alanine aminotransferase, SMD = -0.48; 95% CI: -0.71, -0.25; alkaline phosphatase, SMD = -0.81; 95% CI: -1.55, -0.08), lipid profiles (triglycerides, SMD = -0.22; 95% CI: -0.43, -0.02), and inflammatory factors (high-density lipoprotein, SMD = -0.47; 95% CI: -0.88, -0.06; tumour necrosis factor alpha, SMD = -0.86 95% CI: -1.56, -0.56).

Overall, supplementation with probiotic, prebiotic, or synbiotic had a positive effect on reducing liver enzymes, lipid profiles, and inflammatory cytokines in patients with NAFLD.

Non-alcoholic fatty liver disease (NAFLD1) is the most frequent chronic liver disorder worldwide. Currently, no pharmacological treatment has been approved for NAFLD. Probiotics have been suggested as a potential therapy for NAFLD. The aim of this systematic review and meta-analysis was to assess the impact of probiotic intake on liver tests, lipids, glycemic parameters and inflammatory markers in NAFLD patients.

We searched electronic databases using related terms. Meta-analysis was performed using random-effects models. Clinical outcomes were presented as standard mean difference (SMD2) with a 95 % confidence interval (CI3). Publication bias and heterogeneity were evaluated in eligible studies.

Fifteen randomized clinical trials comprising 899 participants were included in our meta-analysis. Probiotic supplementation improved alanine transaminase [SMD -0.796; 95 % CI (-1.419, -0.172); p = 0.012], Homeostatic Model Assessment for Insulin Resistance (HOMA-IR4) [SMD -0.596; 95 % CI (-1.071, -0.121); p = 0.01] and insulin levels [SMD -1.10; 95 % CI (-2.121, -0.087); p = 0.03]. No significant effects were observed on fasting glucose, hemoglobin A1c, aspartate transaminase, lipid profile, interleukin-6 and tumor necrosis factor-α.

Probiotic intake may improve insulin sensitivity and alanine transaminase in NAFLD patients.

Abrupt dietary change can disrupt the intestinal balance in felines. This study aimed to assess the impact of heat-treated Bifidobacterium longum CECT-7347 combined with Fibersol-2 on the intestinal health of adult cats before and after dietary change. We selected 24 British shorthair cats, dividing them into two groups. From day 1 to day 14, the control group received a lower protein (33%) concentration (LPF) diet, while the treated group received the same LPF diet supplemented with 0.16% functional additives, consisting of Bifidobacterium longum CECT-7347 combined with Fibersol-2. Subsequently, from day 15 to day 28, the control group transitioned to a higher protein (40%) concentration (HPF) diet, while the treated group received the same HPF diet supplemented with 0.16% functional additives. Blood and fresh feces were collected on day 0, 14, 17, 21, and 28 of the experiment. The results suggest that the use of heat-treated Bifidobacterium longum CECT-7347 combined with Fibersol-2 may improve gastrointestinal function in cats by reducing serum LPS levels and fecal pH, while increasing fecal sIgA levels. In addition, the functional additive regulates the fecal microbiota and its function, promoting intestinal homeostasis and colonization with beneficial bacteria such as Blautia. Furthermore, on day 28, there was a significant difference in fecal microbiota beta diversity between the two groups. In summary, the addition of heat-treated Bifidobacterium longum CECT-7347 combined with Fibersol-2 contributes to improving the intestinal health of adult cats affected by abrupt dietary change.

Myriad associations between the microbiome and various facets of liver physiology and pathology have been described in the literature. Building on descriptive and correlative sequencing studies, metagenomic studies are expanding our collective understanding of the functional and mechanistic role of the microbiome as mediators of the gut-liver axis. Based on these mechanisms, the functional activity of the microbiome represents an attractive, tractable, and precision medicine therapeutic target in several liver diseases. Indeed, several therapeutics have been used in liver disease even before their description as a microbiome-dependent approach. To bring successful microbiome-targeted and microbiome-inspired therapies to the clinic, a comprehensive appreciation of the different approaches to influence, collaborate with, or engineer the gut microbiome to coopt a disease-relevant function of interest in the right patient is key. Herein, we describe the various levels at which the microbiome can be targeted-from prebiotics, probiotics, synbiotics, and antibiotics to microbiome reconstitution and precision microbiome engineering. Assimilating data from preclinical animal models, human studies as well as clinical trials, we describe the potential for and rationale behind studying such therapies across several liver diseases, including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, HE as well as liver cancer. Lastly, we discuss lessons learned from previous attempts at developing such therapies, the regulatory framework that needs to be navigated, and the challenges that remain.

Probiotic administration is a promising therapy for improving conditions in NAFLD patients. This network meta-analysis aimed to compare and estimate the relative effects of probiotic interventions and identify the optimal probiotic species for the treatment of NAFLD (Nonalcoholic fatty liver disease) patients.

The PubMed, Web of Science, Embase, and Cochrane databases were searched from inception to 29 January 2024 to identify RCTs that were published in English. The GRADE framework was used to assess the quality of evidence contributing to each network estimate.

A total of 35 RCTs involving 2212 NAFLD patients were included in the analysis. For primary outcomes, Lactobacillus + Bifidobacterium + Streptococcus exhibited the highest probability of being the finest probiotic combination in terms of enhancing acceptability as well as reducing AST (SMD: -1.95 95% CI: -2.90, -0.99), ALT (SMD = -1.67, 95% CI: -2.48, -0.85), and GGT levels (SMD = -2.17, 95% CI: -3.27, -1.06). In terms of the secondary outcomes, Lactobacillus + Bifidobacterium + Streptococcus was also the best probiotic combination for reducing BMI (SMD = -0.45, 95% CI: -0.86, -0.04), LDL levels (SMD = -0.45, 95% CI: -0.87, -0.02), TC levels (SMD = -1.09, 95% CI: -1.89, -0.29), and TNF-α levels (SMD = -1.73, 95% CI: -2.72, -0.74).

This network meta-analysis revealed that Lactobacillus + Bifidobacterium + Streptococcus may be the most effective probiotic combination for the treatment of liver enzymes, lipid profiles, and inflammation factors. These findings can be used to guide the development of a probiotics-based treatment guideline for NAFLD since there are few direct comparisons between different therapies.

To ensure effective administration of probiotics in clinical practice, it is crucial to comprehend the specific strains and their association with human health. Therefore, we conducted a systematic review and meta-analysis to evaluate the scientific evidence on the impact of Lactiplantibacillus plantarum probiotic consumption on human health. Out of 11,831 records, 135 studies were assessed qualitatively, and 18 studies were included in the meta-analysis. This systematic review demonstrated that probiotic supplementation with L. plantarum, either alone or in combination, can significantly improve outcomes for patients with specific medical conditions. Meta-analysis revealed notable benefits in periodontal health, evidenced by reduced pocket depth and bleeding on probing (p < 0.001); in gastroenterological health, marked by significant reductions in abdominal pain (p < 0.001); and in infectious disease, through a reduction in C-reactive protein levels (p < 0.001). Cardiovascular benefits included lowered total cholesterol and low-density lipoprotein cholesterol in the L. plantarum intervention group (p < 0.05). Our study's clinical significance highlights the importance of considering probiotic strain and their application to specific diseases when planning future studies and clinical interventions, emphasizing the need for further research in this area.

The gut microbiota, amounting to approximately 100 trillion (1014) microbes represents a genetic repertoire that is bigger than the human genome itself. Evidence on bidirectional interplay between human and microbial genes is mounting. Microbiota probably play vital roles in diverse aspects of normal human metabolism, such as digestion, immune modulation, and gut endocrine function, as well as in the genesis and progression of many human diseases. Indeed, the gut microbiota has been most closely linked to various chronic ailments affecting the liver, although concrete scientific data are sparse. In this narrative review, we initially discuss the basic epidemiology of gut microbiota and the factors influencing their initial formation in the gut. Subsequently, we delve into the gut-liver axis and the evidence regarding the link between gut microbiota and the genesis or progression of various liver diseases. Finally, we summarise the recent research on plausible ways to modulate the gut microbiota to alter the natural history of liver disease.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.

Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium animalis subsp. lactis V9, and Lactobacillus plantarum P-8) in the treatment of hyperlipidemia.

Thirty three patients with hyperlipidemia were randomly divided into a probiotic group (n = 18) and a control group (n = 15). The probiotic group was administered probiotics (2 g once daily) and atorvastatin 20 mg (once daily), and the control group was administered a placebo (2 g once daily) and atorvastatin 20 mg (once daily). Serum and fecal samples were gathered for subsequent analyses.

Time had a significant effect on the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels in the probiotic and control groups (P < .05). The gut microbial abundance in the probiotic group was markedly higher than that in the control group following 3-month probiotic treatment (P < .05). At the phylum level, probiotics exerted no notable effects on the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria but elevated that of Tenericutes and reduced Proteobacteria. At the genus level, probiotics increased the relative abundance of Bifidobacterium, Lactobacillus, and Akkermansia, and decreased that of Escherichia, Eggerthella, and Sutterella relative to the control group in months 1, 2, and 3 (P < .05).

Probiotics optimize the gut microbiota structure and decrease the amount of harmful bacteria in patients with hyperlipidemia. Probiotics can influence the composition of gut microorganisms and increase their diversity and abundance in vivo. It is recommended to use probiotics combined with atorvastatin to treat patients with hyperlipidemia.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide. Numerous studies conducted recently have demonstrated a connection between the dysbiosis of the development of NAFLD and gut microbiota. Rebuilding a healthy gut ecology has been proposed as a strategy involving the use of probiotics. The purpose of this work is to investigate and compare the function of probiotics Akkermansia muciniphila (A. muciniphila) and VSL#3 in NAFLD mice. Rodent NAFLD was modeled using a methionine choline-deficient diet (MCD) with/without oral probiotic delivery. Subsequently, qPCR, histological staining, and liver function tests were conducted. Mass spectrometry-based analysis and 16S rDNA gene sequencing were used to investigate the liver metabolome and gut microbiota. We found that while both A. muciniphila and VSL#3 reduced hepatic fat content, A. muciniphila outperformed VSL#3. Furthermore, probiotic treatment restored the β diversity of the gut flora and A. muciniphila decreased the abundance of pathogenic bacteria such as Ileibacterium valens. These probiotics altered the metabolism in MCD mice, especially the glycerophospholipid metabolism. In conclusion, our findings distinguished the role of A. muciniphila and VSL#3 in NAFLD and indicated that oral-gavage probiotics remodel gut microbiota and improve metabolism, raising the possibility of using probiotics in the cure of NAFLD.

Considering the increasing prevalence of non-alcoholic steatohepatitis (NASH) and treatment gaps, this study aimed to evaluate the effect of probiotic supplementation on liver function markers, nutritional status, and clinical parameters.

This double-blind, randomized clinical trial (ClinicalTrials.gov ID: NCT0346782) included adult outpatients with biopsy-proven NASH. The intervention consisted of 24 weeks of supplementation with the probiotic mix Lactobacillus acidophilus (1 × 109 CFU) + Lactobacillus rhamnosus (1 × 109 CFU) + Lactobacillus paracasei (1 × 109 CFU) + Bifidobacterium lactis (1 × 109 CFU), or placebo, twice a day. The following parameters were evaluated: demographic and clinical data, transient elastography (FibroScan), liver enzymes, NAFLD fibrosis score, fatty liver index, laboratory assessment, serum concentration of toll-like receptor-4 (sTLR-4) and cytokeratin 18 (CK-18), anthropometric data, dietary intake, and physical activity. Regarding data analysis, the comparison between the groups was based on the delta of the difference of each variable analyzed (value at the end of treatment minus the baseline value) using the t-test for independent samples or the Mann-Whitney U-test.

Forty-four patients with NASH completed the trial (51.4 ± 11.6 years). At baseline, 87% of participants had a mild liver fibrosis degree on biopsy, normal values of liver enzymes, transient elastography values consistent with grade 1 fibrosis in both groups, increased waist circumference (WC), a BMI of 30.97 kg/m2, and 76% presented with metabolic syndrome (MetS). After the intervention, no differences were observed between the probiotic and placebo groups in terms of MetS, WC, BMI scores, or liver enzyme levels (p > 0.05 for all). The elastography values remained consistent with grade 1 fibrosis in both groups. Although CK-18 was reduced in both groups, a larger effect size was noted in the probiotic group (D = 1.336). sTLR-4 was also reduced in both groups, with no difference between groups (p = 0.885).

Intervention with probiotics in the early stages of NASH demonstrated no significant change in hepatic and clinical parameters.

ClinicalTrials.gov, identifier NCT0346782.

Second-generation antipsychotics are mainly used in both acute and long-term treatment of major psychiatric disorders. Although better tolerated than first-generation antipsychotic drugs, they can frequently induce weight gain and metabolic disorders, of these, olanzapine is one of the drugs more likely to induce these side effects. There is consistent evidence of the role of gut microbiota in modulating the gut-brain axis with complex crosstalk with the host involving satiety signaling pathways, food intake behavior, and weight and metabolic regulation. Second-generation antipsychotics induce important gut microbiota modification thus contributing together with the central and peripheral receptors blockade mechanism to weight gain induction and metabolic impairment. These drugs can alter the composition of gut microbiota and induce dysbiosis, often reducing the concentration of Akkermansia muciniphila, a bacterium that is also decreased in patients with diabetes, obesity, metabolic syndrome, or chronic inflammatory diseases. Probiotic administration can be a safe and well-tolerated approach to modulate microbiota and offer an integrative strategy in psychiatric patients suffering antipsychotic side effects. Multiple strain probiotics and Akkermansia muciniphila alone have been administered both in mice models and in clinical populations demonstrating efficacy on antipsychotic-induced metabolic impairment and showing a contribution in reducing induced weight gain. Akkermansia muciniphila can improve several parameters altered by olanzapine administration, such as weight gain, insulin resistance, hyperglycemia, liver function, systemic inflammation, and gut barrier function. Although we do not have jet trials in the psychiatric population, this probiotic may be a complementary approach to treating olanzapine-induced weight gain and metabolic side effects.

Oral microbiome dysbiosis mediates chronic periodontal disease, gut microbial dysbiosis, and mucosal barrier disfunction that leads to steatohepatitis via the enterohepatic circulation. Improving this dysbiosis towards health may improve liver disease. Treatment with antibiotics and probiotics have been used to modulate the microbial, immunological, and clinical landscape of periodontal disease with some success. The aim of the present investigation was to evaluate the potential for nisin, an antimicrobial peptide produced by Lactococcus lactis, to counteract the periodontitis-associated gut dysbiosis and to modulate the glycolipid-metabolism and inflammation in the liver. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum, were administrated topically onto the oral cavity to establish polymicrobial periodontal disease in mice. In the context of disease, nisin treatment significantly shifted the microbiome towards a new composition, commensurate with health while preventing the harmful inflammation in the small intestine concomitant with decreased villi structural integrity, and heightened hepatic exposure to bacteria and lipid and malondialdehyde accumulation in the liver. Validation with RNA Seq analyses, confirmed the significant infection-related alteration of several genes involved in mitochondrial dysregulation, oxidative phosphorylation, and metal/iron binding and their restitution following nisin treatment. In support of these in vivo findings indicating that periodontopathogens induce gastrointestinal and liver distant organ lesions, human autopsy specimens demonstrated a correlation between tooth loss and severity of liver disease. Nisin's ability to shift the gut and liver microbiome towards a new state commensurate with health while mitigating enteritis, represents a novel approach to treating NAFLD-steatohepatitis-associated periodontal disease.

Gut microbiota exert influence on gastrointestinal mucosal permeability, bile acid metabolism, short-chain fatty acid synthesis, dietary fiber fermentation, and farnesoid X receptor/Takeda G protein-coupled receptor 5 (TGR5) signal transduction. The incretin glucagon-like peptide 1 (GLP-1) is mainly produced by L cells in the gut and regulates postprandial blood glucose. Changes in gut microbiota composition and function have been observed in obesity and type 2 diabetes (T2D). Meanwhile, the function and rhythm of GLP-1 have also been affected in subjects with obesity or T2D. Therefore, it is necessary to discuss the link between the gut microbiome and GLP-1. In this review, we describe the interaction between GLP-1 and the gut microbiota in metabolic diseases. On the one hand, gut microbiota metabolites stimulate GLP-1 secretion, and gut microbiota affect GLP-1 function and rhythm. On the other hand, the mechanism of action of GLP-1 on gut microbiota involves the inflammatory response. Additionally, we discuss the effects and mechanism of various interventions, such as prebiotics, probiotics, antidiabetic drugs, and bariatric surgery, on the crosstalk between gut microbiota and GLP-1. Finally, we stress that gut microbiota can be used as a target for metabolic diseases, and the clinical application of GLP-1 receptor agonists should be individualized.

To compare the effects of probiotics on liver stiffness and steatosis in obese and non-obese patients with nonalcoholic fatty liver disease (NAFLD),the pragmatic clinical trial included 50 obese body mass index (BMI) ≥25 kg/m2 and 50 non-obese NAFLD BMI <25 kg/m2 age and sex-matched patients.

Fibroscan with controlled attenuated parameter (CAP) was done at day 0 and at the end of 6 months. Probiotics supplementation was provided for both groups for 6 months along with lifestyle modifications.

At inclusion, both groups had comparable characteristics except BMI, metabolic syndrome and waist circumference (WC). Beneficial changes occurred in BMI (p=0.024), WC (p=0.045), ALT (p=0.024), total cholesterol (p=0.016), LDL (p=0.025) and triglyceride (p=0.021) of obese group, systolic blood pressure (p=0.003) and LDL level (p=0.018) in non-obese group. No significant change was observed in liver enzymes and glycemic profiles. Significant improvement in CAP was observed in both groups. But after adjusting for changes in BMI and WC, the change in CAP among non-obese participants were significantly higher compared to obese, mean change of 19.33±48.87 and 16.02±51.58 dB/m in non-obese and obese patients, respectively; p=0.044).

Probiotics improve CAP/ steatosis in both obese and non-obese NAFLD patients and improvement was higher in non-obese, irrespective of BMI change.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.

This review provides a practical and comprehensive overview of non-pharmacological interventions for metabolic-associated fatty liver disease (MASLD), focusing on dietary and exercise strategies. It highlights the effectiveness of coffee consumption, intermittent fasting, and Mediterranean and ketogenic diets in improving metabolic and liver health. The review emphasizes the importance of combining aerobic and resistance training as a critical approach to reducing liver fat and increasing insulin sensitivity. Additionally, it discusses the synergy between diet and exercise in enhancing liver parameters and the role of gut microbiota in MASLD. The paper underscores the need for a holistic, individualized approach, integrating diet, exercise, gut health, and patient motivation. It also highlights the long-term benefits and minimal risks of lifestyle interventions compared to the side effects of pharmacological and surgical options. The review calls for personalized treatment strategies, continuous patient education, and further research to optimize therapeutic outcomes in MASLD management.

The prevalence of overweight, obesity, type 2 diabetes, metabolic syndrome and steatotic liver disease is rapidly increasing worldwide with a huge economic burden in terms of morbidity and mortality. Several genetic and environmental factors are involved in the onset and development of metabolic disorders and related complications. A critical role also exists for the gut microbiota, a complex polymicrobial ecology at the interface of the internal and external environment. The gut microbiota contributes to food digestion and transformation, caloric intake, and immune response of the host, keeping the homeostatic control in health. Mechanisms of disease include enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability and translocation of bacterial metabolites which activate a chronic low-grade systemic inflammation and insulin resistance, as precursors of tangible metabolic disorders involving glucose and lipid homeostasis. The ultimate causative role of gut microbiota in this respect remains to be elucidated, as well as the therapeutic value of manipulating the gut microbiota by diet, pre- and pro- synbiotics, or fecal microbial transplantation.

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

In recent decades, the global prevalence of metabolic syndrome has surged, posing a significant public health challenge. Metabolic disorders, encompassing diabetes, obesity, nonalcoholic fatty liver disease, and polycystic ovarian syndrome, have been linked to alterations in the gut microbiota. Nonetheless, the connection between gut microbiota and host metabolic diseases warrants further investigation. In this review, we delve into the associations between various metabolic disorders and the gut microbiota, focusing on immune responses and bile acid (BA) metabolism. Notably, T helper cells, innate lymphoid cells, macrophages, and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines. Furthermore, secondary BA metabolites, derived from the microbiota, are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5. By covering both aspects of this immune system-microorganism axis, we present a comprehensive overview of the roles played by the gut microbiota, microbiota-derived BA metabolites, and immune responses in metabolic diseases, as well as the interplay between these systems.

Modulation of the gut microbiome composition with probiotics may have beneficial metabolic effects in pregnant women with obesity. The aim was to investigate the effect of probiotic supplementation during pregnancy on metabolic and inflammatory markers and the body composition of the offspring.

A randomized double-blind trial in 50 pregnant women (pre-pregnancy BMI ≥30 and < 35 kg/m2) comparing multi-strain probiotics (Vivomixx®; 450 billion CFU/d) versus placebo from 14 to 20 weeks of gestation until delivery was carried out. Participants were followed with two predelivery visits at gestational week 27-30 and 36-37 and with one postdelivery visit. All visits included fasting blood samples (C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin, C-peptide, glucose, glucagon, and glucagon-like peptide-1 (GLP-1)). At delivery, umbilical cord blood samples were collected (GLP-1 and glucagon). At the postdelivery visit, a dual-energy X-ray absorptiometry (DXA) scan of the newborn was performed. Forty-nine of 50 participants completed the study until delivery, and 36 mother-offspring dyads underwent postdelivery examinations including a DXA scan. There were no significant differences in changes in measured biomarkers between the probiotic versus the placebo group. No differences were found in newborn body composition or GLP-1 and glucagon. GLP-1 measured in umbilical blood samples was positively correlated to fat percent in offspring from the probiotic group.

In this study of pregnant women with obesity and their newborns, there was no effect of probiotic supplementation in mothers or babies on metabolic or inflammatory biomarkers or on body composition of offspring. This study was registered at clinicaltrials.gov as NCT02508844.

In recent years, the obesity epidemic has escalated into a serious public health catastrophe that is only getting worse. However, research into the pathophysiological pathways behind the obesity development and the illnesses that it is associated with is ongoing. In the last decades, it is now clear that the gut microbiota plays a significant role in the genesis and progression of obesity and obesity-related illnesses, particularly changes in its metabolites and composition as obesity progresses. Here, we provide a summary of the processes by which variations in gut metabolite levels and the composition of gut microbiota affect obesity and associated disorders. The bacteria residing in the gut release several chemicals that influence the appetite control, metabolism, and other systems. Since it can either encourage or restrict the deposition of fat in several different ways, the gut microbiota's role in obesity is debatable. Additionally, we go over potential therapeutic approaches that could be utilized to alter gut microbiota composition and focus on the important metabolic pathways associated with obesity and metabolic disorders linked to obesity.