Current pharmacological treatments for metabolic dysfunction-associated steatotic liver disease (MASLD) are often accompanied by adverse side effects. Consequently, probiotics, prebiotics, and synbiotics, which are bioactive compounds from fermented foods and offer fewer side effects, have garnered significant attention as alternative therapeutic strategies.

This study aims to assess the efficacy of microbial therapies-probiotics, prebiotics, and synbiotics-in managing MASLD and to identify the optimal treatment modality for various clinical indicators through a comprehensive umbrella review of meta-analyses.

A thorough literature search was conducted across PubMed, Web of Science, EMBASE, Cochrane Library, and Scopus to identify 23 meta-analyses over 18,999 MASLD patients as of November 2024.

The findings indicate that microbial treatments positively influence levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), homeostasis model assessment of insulin resistance (HOMA-IR), insulin, tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and body mass index (BMI) in MASLD patients. Notably, probiotics were most effective in reducing TC, ALT, AST, GGT, insulin, TNF-α, and BMI; prebiotics were most effective in reducing TG; and synbiotics were most effective in reducing LDL-C, HOMA-IR, and CRP.

Our study provides robust evidence for microbial treatments of MASLD, enabling targeted interventions for different indicators.

Numerous recent studies have suggested that the composition of the intestinal microbiota can trigger metabolic disorders, such as diabetes, prediabetes, obesity, metabolic syndrome, sarcopenia, dyslipidemia, hyperhomocysteinemia, and non-alcoholic fatty liver disease. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and metabolic disorders, as well as the role of probiotics in the modulation of the intestinal microbiota. The aim of this review was to summarize the reviews and individual articles on the state of the art regarding ideal therapy with probiotics and prebiotics in order to obtain the reversion of dysbiosis (alteration in microbiota) to eubiosis during metabolic diseases, such as diabetes, prediabetes, obesity, hyperhomocysteinemia, dyslipidemia, sarcopenia, and non-alcoholic fatty liver diseases. This review includes 245 eligible studies. In conclusion, a condition of dysbiosis, or in general, alteration of the intestinal microbiota, could be implicated in the development of metabolic disorders through different mechanisms, mainly linked to the release of pro-inflammatory factors. Several studies have already demonstrated the potential of using probiotics and prebiotics in the treatment of this condition, detecting significant improvements in the specific symptoms of metabolic diseases. These findings reinforce the hypothesis that a condition of dysbiosis can lead to a generalized inflammatory picture with negative consequences on different organs and systems. Moreover, this review confirms that the beneficial effects of probiotics on metabolic diseases are promising, but more research is needed to determine the optimal probiotic strains, doses, and administration forms for specific metabolic conditions.

Many studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease (NAFLD). Therefore, we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the association between serum carotenoids and NAFLD in adults.

This 7.8-year prospective study included 2921 participants with serum carotenoids at baseline and determined NAFLD by ultrasonography (ULS-NAFLD) every 3 years. A total of 828 subjects additionally underwent magnetic resonance imaging to identify NAFLD (MRI-NAFLD). Gut microbiota was analyzed by 16S rRNA sequencing in 1,661 participants, and targeted metabolomics profiling in 893 feces and 896 serum samples was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the middle term.

A total of 2,522 participants finished follow-up visits. Of these participants, 770, 301, 474, and 977 were categorized into NAFLD-free, improved, new-onset, and persistent NAFLD groups based on their ULS-NAFLD status changes, respectively, and 342/828 were MRI-verified NALFD. Longitudinal analyses showed an inverse association between carotenoids and NALFD risk/presence (P-trend <0.05). Multivariable-adjusted odds ratios (ORs)/hazard ratio (HR) [95% confidence intervals (CIs)] of NAFLD for quartile 4 (vs. quartile 1) of total carotenoids were 0.63 (0.50, 0.80) for incident ULS-NAFLD, 0.20 (0.15, 0.27) for persistent ULS-NAFLD, 1.53 (1.10, 2.12) for improved-NAFLD, and 0.58 (0.39, 0.87) for MRI-NAFLD. The biomarkers in the gut-liver axis significantly associated with both serum carotenoids and NAFLD included sixteen microbial genera mainly in Ruminococcaceae and Veillonellaceae family, nineteen fecal metabolites containing medium-chain fatty acids (MCFAs), bile acids, and carnitines, and sixteen serum metabolites belonging to organic acids and amino acids. The total carotenoids-related scores of significant microbial genera, fecal and serum metabolites mediated the carotenoids-NAFLD association by 8.72%, 12.30%, and 16.83% (all P<0.05) for persistent NAFLD and 9.46%, 8.74%, and 15.7% for incident-NAFLD, respectively.

Our study reveals a beneficial association of serum carotenoids and incident and persistent NAFLD. The identified gut-liver axis biomarkers provided mechanistic linkage for the epidemiological association.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies' potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.

The study aimed to comprehensively analyze and establish a framework for evaluating the efficacy of microbiome-targeted treatment (MTT) for depression.

We searched PubMed, Embase, Cochrane Library, Web of Science, and the Chinese National Knowledge Infrastructure database for randomized controlled trials (RCTs) on MTT in treating depression until October 19, 2023. A meta-analysis was conducted to evaluate the efficacy and safety of MTT. Comprehensive subgroup analyses were undertaken to explore factors influencing MTT's efficacy in treating depression. This study was registered with PROSPERO (CRD42023483649).

The study selection process identified 51,570 studies, of which 34 met the inclusion criteria. The overall pooled estimates showed that MTT significantly improved depression symptoms (SMD -0.26, 95% CI [-0.32, -0.19], I2 = 54%) with acceptable safety. Subgroup analyses by geography showed that effectiveness was demonstrated in Asia (SMD -0.46, 95% CI [-0.56, -0.36], I2 = 36%), while no evidence of effectiveness was found in Europe (SMD -0.07, 95% CI [-0.19, 0.05], I2 = 55%), America (SMD -0.33, 95% CI [-0.67, 0.02], I2 = 60%), and Oceania (SMD 0.00, 95% CI [-0.18, 0.18], I2 = 0%). Besides, the efficacy was shown in depressed patients without comorbidities (SMD -0.31, 95% CI [-0.40, -0.22], I2 = 0%), whereas effectiveness was poor in those with digestive disorders, such as irritable bowel syndrome (SMD -0.37, 95% CI [-0.89, 0.16], I2 = 74%), chronic diarrhea (SMD -0.34, 95% CI [-0.73, 0.05]), and chronic constipation (SMD -0.23, 95% CI [-0.57, 0.11], I2 = 0%). In perinatal depressed patients, MTT was not effective (SMD 0.16, 95% CI [0.01, 0.31], I2 = 0%). It was found that < 8 weeks (SMD -0.33, 95% CI [-0.45, -0.22], I2 = 0%) and 8-12 weeks (SMD -0.34, 95% CI [-0.44, -0.23], I2 = 57%) MTT were effective, while > 12 weeks (SMD 0.02, 95% CI [-0.12, 0.17], I2 = 68%) MTT was ineffective.

Despite the overall effectiveness of MTT in treating depression and its acceptable safety profile, caution is warranted in drawing this conclusion due to limitations posed by the small sample size of included studies and heterogeneity. The efficacy of MTT for depression exhibits variation influenced by geography, patient comorbidities, and duration of administration.

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.

Periodontitis is increasingly recognized for its role in overall health and its associations with systemic conditions. Shared etiological factors, including microbiological, immunological, genetic, and environmental influences, have prompted interest in the potential impact of periodontal therapy on broader health outcomes. The oral microbiome plays a key role in the pathogenesis of periodontitis, with microbial imbalances (dysbiosis) contributing to inflammation and systemic disease progression. Additionally, immune responses to periodontal infection, such as chronic inflammation and dysregulated immune activity, are central to linking periodontitis with conditions like diabetes, cardiovascular disease, and autoimmune disorders. This chapter explores the connections between periodontal treatment and systemic diseases, such as diabetes, rheumatoid arthritis, cardiovascular disease, chronic kidney disease, Alzheimer's disease, digestive disorders, and respiratory disease. It also reviews the current research on the mechanisms, including microbial and immune factors, that underlie these associations. By emphasizing the role of periodontal health, the oral microbiome, and immune regulation in disease prevention and management, this chapter underscores the importance of integrated healthcare approaches to improve patient outcomes.

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.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-previously described as nonalcoholic fatty liver disease-continues to rise globally. Despite this, therapeutic measures for MASLD remain limited. Recently, there has been a growing interest in the gut microbiome's role in the pathogenesis of MASLD. Understanding this relationship may allow for the administration of therapeutics that target the gut microbiome and/or its metabolic function to alleviate MASLD development or progression. This review will discuss the interplay between the gut microbiome's structure and function in relation to the development of MASLD, assess the diagnostic yield of gut microbiome-based signatures as a noninvasive tool to identify MASLD severity, and examine current and emerging therapies targeting the gut microbiome-liver axis.

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.

Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, we will review the effects of lifestyle interventions commonly used for MASLD (i.e. Mediterranean diet and physical exercise) on gut microbiome, to understand if their beneficial effect can be microbially mediated. Finally, we will discuss the role and the available evidence of therapeutic microbiome modulators, including prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT), in the management of MASLD.

Currently, there are no authorized medications specifically for non-alcoholic fatty liver disease (NAFLD) treatment. Studies indicate that changes in gut microbiota can disturb intestinal balance and impair the immune system and metabolism, thereby elevating the risk of developing and exacerbating NAFLD. Despite some debate, the potential benefits of microbial therapies in managing NAFLD have been shown.

A systematic search was undertaken to identify meta-analyses of randomized controlled trials that explored the effects of microbial therapy on the NAFLD population. The goal was to synthesize the existing evidence-based knowledge in this field.

The results revealed that probiotics played a significant role in various aspects, including a reduction in liver stiffness (MD: -0.38, 95% CI: [-0.49, -0.26]), hepatic steatosis (OR: 4.87, 95% CI: [1.85, 12.79]), decrease in body mass index (MD: -1.46, 95% CI: [-2.43, -0.48]), diminished waist circumference (MD: -1.81, 95% CI: [-3.18, -0.43]), lowered alanine aminotransferase levels (MD: -13.40, 95% CI: [-17.02, -9.77]), decreased aspartate aminotransferase levels (MD: -13.54, 95% CI: [-17.85, -9.22]), lowered total cholesterol levels (MD: -15.38, 95% CI: [-26.49, -4.26]), decreased fasting plasma glucose levels (MD: -4.98, 95% CI: [-9.94, -0.01]), reduced fasting insulin (MD: -1.32, 95% CI: [-2.42, -0.21]), and a decline in homeostatic model assessment of insulin resistance (MD: -0.42, 95% CI: [-0.72, -0.11]) (P<0.05).

Overall, the results demonstrated that gut microbiota interventions could ameliorate a wide range of indicators including glycemic profile, dyslipidemia, anthropometric indices, and liver injury, allowing them to be considered a promising treatment strategy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is constantly rising globally. There are barely any effective medications or supplements for the management of MASLD. We aim to systematically evaluate the most current evidence for gut microbiota-regulating supplements in patients with MASLD.

We searched multiple electronic data for randomized controlled trials (RCTs) published from January 1, 2012, to July 15, 2023. The intervention measures included probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The control group was treated with a placebo or usual care. The intervention duration was divided into two periods (>12 weeks and ≤12 weeks). Adequate evaluation data for antibiotics and FMT have not been obtained. Therefore, the other three microbiota regulators are the primary evaluation measures in this study.

We found that probiotics alone could not improve clinical indicators in MASLD patients. However, synbiotics exhibited an improvement in reducing liver steatosis, TNF-ɑ levels, and increasing HDL-c levels, and the inflammatory markers of liver cells (ALT and AST) were also improved. For the effective intervention duration, this systematic review suggested that around 12 weeks is an ideal intervention cycle for MASLD patients.

This meta-analysis supported the modulation of gut microbiota with synbiotics in the management of MASLD.

Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.

With the rapid development of histological techniques and the widespread application of single-cell sequencing in eukaryotes, researchers desire to explore individual microbial genotypes and functional expression, which deepens our understanding of microorganisms. In this review, the history of the development of microbial detection technologies was revealed and the difficulties in the application of single-cell sequencing in microorganisms were dissected as well. Moreover, the characteristics of the currently emerging microbial single-cell sequencing (Microbe-seq) technology were summarized, and the prospects of the application of Microbe-seq in microorganisms were distilled based on the current development status. Despite its mature development, the Microbe-seq technology was still in the optimization stage. A retrospective study was conducted, aiming to promote the widespread application of single-cell sequencing in microorganisms and facilitate further improvement in the technology.

The development of steatotic liver disease after liver transplant (LT) is widely described, and epidemiological data have revealed an increased incidence in recent times. Its evolution runs from simple steatosis to steatohepatitis and, in a small proportion of patients, to significant fibrosis and cirrhosis. Apparently, post-LT steatotic disease has no impact on the recipient's overall survival; however, a higher cardiovascular and malignancy burden has been reported. Many donors' and recipients' risk factors have been associated with this occurrence, although the recipient-related ones seem of greater impact. Particularly, pre- and post-LT metabolic alterations are strictly associated with steatotic graft disease, sharing common pathophysiologic mechanisms that converge on insulin resistance. Other relevant risk factors include genetic variants, sex, age, baseline liver diseases, and immunosuppressive drugs. Diagnostic evaluation relies on liver biopsy, although non-invasive methods are being increasingly used to detect and monitor both steatosis and fibrosis stages. Management requires a multifaceted approach focusing on lifestyle modifications, the optimization of immunosuppressive therapy, and the management of metabolic complications. This review aims to synthesize the current knowledge of post-LT steatotic liver disease, focusing on the recent definition of metabolic-dysfunction-associated steatotic liver disease (MASLD) and its metabolic and multisystemic concerns.

The terms non-alcoholic fatty liver disease and non-alcoholic steatohepatitis have some limitations as they use exclusionary confounder terms and the use of potentially stigmatising language. Recently, a study with content experts and patients has been set to change this nomenclature. The term chosen to replace non-alcoholic fatty liver disease was metabolic dysfunction-associated steatotic liver disease (MASLD), which avoids stigmatising and helps improve awareness and patient identification. MASLD is the most common cause of chronic liver disease with an increasing prevalence, accounting for 25% of the global population. It is considered the hepatic manifestation of the metabolic syndrome with lifestyle playing a fundamental role in its physiopathology. Diet change and physical activity are the cornerstones of treatment, encompassing weight loss and healthier behaviours and a holistic approach. In Europe, there is no approved drug for MASLD to date and there is a substantial unmet medical need for effective treatments for patients with MASLD. This review not only provides an update on advances in evidence for nutrition and physical activity interventions but also explores the different therapeutic options that are being investigated and whose development focuses on the restitution of metabolic derangements and halting inflammatory and fibrogenic pathways.

Nonalcoholic steatohepatitis (NASH) is characterized by liver steatosis, inflammation, and even fibrosis. NASH is likely to develop into cirrhosis and liver cancer, the major causes of liver related deaths. We aimed to study the effect of probiotics on NASH via the gut-liver axis.

Thirty male Sprague-Dawley rats were divided into three groups. A control group of 10 rats was fed on a standard chow for 16 weeks. Twenty rats fed on a high-fat diet for 8 weeks were separated to two groups: a model group (10 rats) fed on vehicle for 8 weeks and a treatment group (10 rats) supplemented with binary Bacillus subtilis for 8 weeks. Hepatic expression of IL-6 and TNF-ɑ and ileum expression of IL-17 and occludin were measured.

The high-fat diet caused inflammation of the liver and ileum in rats. Binary Bacillus subtilis treatment reduces liver inflammation through the intestinal liver axis. Increased levels of IL-6 and TNF-α were detected in rats fed a high-fat diet, which were reduced to lower levels after treatment with binary Bacillus subtilis. In rats on the high-fat diet, elevated IL-17 levels and decreased occludin levels were observed. Treatment with Bacillus subtilis reduced IL-17 levels and restored the expression of occludin.

Binary Bacillus subtilis has a beneficial effect on liver inflammation and intestinal damage.

Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome-targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear.

This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population.

A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD.

Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies.

A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], -10.21; 95% confidence interval [CI], -13.29, -7.14; P < 0.001), aspartate aminotransferase (AST; ES, -8.86; 95%CI, -11.39, -6.32; P < 0.001), and γ-glutamyltransferase (ES, -5.56; 95%CI, -7.92, -3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, -8.69; 95%CI, -11.01, -6.37; P < 0.001) and ALT (ES, -9.82; 95%CI, -11.59, -8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, -11.40; 95%CI, -13.91, -8.88; P < 0.001) and ALT (ES, -11.87; 95%CI, -13.80, -9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, -2.96; 95%CI, -8.12, 2.18, P = 0.259; and ES, -4.69; 95%CI, -13.53, 4.15, P = 0.299, respectively).

Gut microbiome-targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome-targeted therapies in the treatment of the NAFLD population.

PROSPERO registration no. CRD42022346998.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for non-alcoholic fatty liver disease (NAFLD). Increased fasting blood sugar (FBS), fasting insulin (FI), and insulin resistance (HOMA-IR) are observed in patients with NAFLD. Gut microbial modulation using prebiotics, probiotics, and synbiotics has shown promise in NAFLD treatment. This meta-umbrella study aimed to investigate the effects of gut microbial modulation on glycemic indices in patients with NAFLD and discuss potential mechanisms of action.

A systematic search was conducted in PubMed, Web of Science, Scopus, and Cochrane Library until March 2023 for meta-analyses evaluating the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD. Random-effect models, sensitivity analysis, and subgroup analysis were employed.

Gut microbial therapy significantly decreased HOMA-IR (ES: -0.41; 95%CI: -0.52, -0.31; P < 0.001) and FI (ES: -0.59; 95%CI: -0.77, -0.41; P < 0.001). However, no significant effect was observed on FBS (ES: -0.17; 95%CI: -0.36, 0.02; P = 0.082). Subgroup analysis revealed prebiotics had the most potent effect on HOMA-IR, followed by probiotics and synbiotics. For FI, synbiotics had the most substantial effect, followed by prebiotics and probiotics.

Probiotics, prebiotics, and synbiotics administration significantly reduced FI and HOMA-IR, but no significant effect was observed on FBS.

Modulating the gut microbiota population by administration of probiotics, prebiotics, and synbiotics has shown to have a variety of health benefits in different populations, particularly those with metabolic disorders. Although the promising effects of these compounds have been observed in the management of patients with non-alcoholic fatty liver disease (NAFLD), the exact effects and the mechanisms of action are yet to be understood. In the present study, we aimed to evaluate how gut microbiota modulation affects anthropometric indices of NAFLD patients to achieve a comprehensive summary of current evidence-based knowledge.

Two researchers independently searched international databases, including PubMed, Scopus, and Web of Science, from inception to June 2023. Meta-analysis studies that evaluated the effects of probiotics, prebiotics, and synbiotics on patients with NAFLD were entered into our umbrella review. The data regarding anthropometric indices, including body mass index, weight, waist circumference (WC), and waist-to-hip ratio (WHR), were extracted by the investigators. The authors used random effect model for conducting the meta-analysis. Subgroup analysis and sensitivity analysis were also performed.

A total number of 13 studies were finally included in our study. Based on the final results, BMI was significantly decreased in NAFLD patients by modulation of gut microbiota [effect size (ES): -0.18, 05% CI: -0.25, -0.11, P<0.001]; however, no significant alteration was observed in weight and WC (ES: -1.72, 05% CI: -3.48, 0.03, P=0.055, and ES: -0.24, 05% CI: -0.75, 0.26, P=0.353, respectively). The results of subgroup analysis showed probiotics had the most substantial effect on decreasing BMI (ES: -0.77, 95% CI: -1.16, -0.38, P<0.001) followed by prebiotics (ES: -0.51, 95% CI: -0.76, -0.27, P<0.001) and synbiotics (ES: -0.12, 95% CI: -0.20, -0.04, P=0.001).

In conclusion, the present umbrella meta-analysis showed that although modulation of gut microbiota by administration of probiotics, prebiotics, and synbiotics had promising effects on BMI, no significant change was observed in the WC and weight of the patients. No sufficient data were available for other anthropometric indices including waist-to-hip ratio and waist-to-height ratio and future meta-analyses should be done in this regard.

Purpose: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment of NAFLD. The new mechanism of "Shenling Baizhu San" (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level. Methods: Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl4 injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics. Results: SLBZS intervention for 6 weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (Bifidobacterium and Parvibacter) and inhibiting the growth of pro-inflammatory bacteria (Erysipelatoclostridium and Lachnoclostridium) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS. Conclusion: Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic condition whose impact on human health is increasingly significant. The imbalance of the gut microbiome, linked to insulin resistance, heightened intestinal permeability, and pro-inflammatory reactions, may be the linchpin in the development of NAFLD. In our research, the impact of Lactiplantibacillus plantarum ZDY2013 administration for 12 weeks on gut microbiota dysbiosis induced by a high-fat, high-fructose, high-cholesterol (FHHC) diet in male C57BL/6n mice was investigated. Research results presented that the intervention of L. plantarum ZDY2013 in mice fed with the FHHC diet could restore their liver function and regulate oxidative stress. Compared to mice in the model group, the intervention of L. plantarum ZDY2013 significantly regulated the gut microbiota, inhibited the LPS/NF-κB pathway, and led to a lower level of colonic inflammation in the mice administered with L. plantarum ZDY2013. It also improved insulin resistance to regulate the PI3K/Akt pathway and lipid metabolism, thereby resulting in reduced fat accumulation in the liver. The above results suggest that the intervention of L. plantarum ZDY2013 can hinder the progression of diet-induced NAFLD by reducing inflammation to regulate the PI3K/Akt pathway and regulating gut microbiota disturbance.

There is controversial data on the effects of prebiotic, probiotic, or synbiotic supplementations on overweight/obesity indicators. Thus, we aimed to clarify this role of biotics through an umbrella review of the trials' meta-analyses.

All meta-analyses of the clinical trials conducted on the impact of biotics on overweight/obesity indicators in general populations, pregnant women, and infants published until June 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. The meta-analysis of observational and systematic review studies without meta-analysis were excluded. We reported the results by implementing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flowchart. The Assessment of Multiple Systematic Reviews-2 (AMSTAR2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological quality and quality of evidence.

Overall, 97 meta-analysis studies were included. Most studies were conducted on the effect of probiotics in both genders. Consumption of prebiotic: 8-66 g/day, probiotic: 104 -1.35×1015 colony-forming unit (CFU)/day, and synbiotic: 106-1.5×1011 CFU/day and 0.5-300 g/day for 2 to 104 weeks showed a favorable effect on the overweight/obesity indicators. Moreover, an inverse association was observed between biotics consumption and overweight/obesity risk in adults in most of the studies. Biotics did not show any beneficial effect on weight and body mass index (BMI) in pregnant women by 6.6×105-1010 CFU/day of probiotics during 1-25 weeks and 1×109-112.5×109 CFU/capsule of synbiotics during 4-8 weeks. The effect of biotics on weight and BMI in infants is predominantly non-significant. Prebiotics and probiotics used in infancy were from 0.15 to 0.8 g/dL and 2×106-6×109 CFU/day for 2-24 weeks, respectively.

It seems biotics consumption can result in favorable impacts on some anthropometric indices of overweight/obesity (body weight, BMI, waist circumference) in the general population, without any significant effects on birth weight or weight gain during pregnancy and infancy. So, it is recommended to intake the biotics as complementary medications for reducing anthropometric indices of overweight/obese adults. However, more well-designed trials are needed to elucidate the anti-obesity effects of specific strains of probiotics.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a replacement of the nomenclature employed for NAFLD, is the most prevalent chronic liver disease worldwide. Despite its high global prevalence, NAFLD is often under-recognized due to the absence of reliable noninvasive biomarkers for diagnosis and staging. Growing evidence suggests that the gut microbiome plays a significant role in the occurrence and progression of NAFLD by causing immune dysregulation and metabolic alterations due to gut dysbiosis. The rapid advancement of sequencing tools and metabolomics has enabled the identification of alterations in microbiome signatures and gut microbiota-derived metabolite profiles in numerous clinical studies related to NAFLD. Overall, these studies have shown a decrease in α-diversity and changes in gut microbiota abundance, characterized by increased levels of Escherichia and Prevotella, and decreased levels of Akkermansia muciniphila and Faecalibacterium in patients with NAFLD. Furthermore, bile acids, short-chain fatty acids, trimethylamine N-oxide, and tryptophan metabolites are believed to be closely associated with the onset and progression of NAFLD. In this review, we provide novel insights into the vital role of gut microbiome in the pathogenesis of NAFLD. Specifically, we summarize the major classes of gut microbiota and metabolic biomarkers in NAFLD, thereby highlighting the links between specific bacterial species and certain gut microbiota-derived metabolites in patients with NAFLD.

Trichinella spiralis is recognized for its ability to regulate host immune responses. The serine protease inhibitor of T. spiralis (Ts-SPI) participates in T. spiralis-mediated immunoregulatory effects. Studies have shown that helminth therapy exhibits therapeutic effects on metabolic diseases. In addition, we previously found that T. spiralis-derived crude antigens could alleviate diet-induced obesity. Thus, Ts-SPI was hypothesized to alleviate non-alcoholic fatty liver disease (NAFLD). Herein, recombinant Ts-SPI (rTs-SPI) was prepared from the muscle larvae T. spiralis. The relative molecular mass of rTs-SPI was approximately 35,000 Da, and western blot analysis indicated good immunoreactivity. rTs-SPI ameliorated hepatic steatosis, inflammation, and pyroptosis in NAFLD mice, which validated the hypothesis. rTs-SPI also reduced macrophage infiltration, significantly expanded Foxp3+ Treg population, and inactivated TLR4/NF-κB/NLRP3 signaling in the liver. Furthermore, rTs-SPI treatment significantly shifted the gut microbiome structure, with a remarkable increase in beneficial bacteria and reduction in harmful bacteria to improve gut barrier integrity. Finally, Abx-treated mice and FMT confirmed that gut-liver crosstalk contributed to NAFLD improvement after rTs-SPI treatment. Taken together, Taken together, these findings suggest that rTs-SPI exerts therapeutic effects in NAFLD via anti-inflammatory activity and gut-liver crosstalk.

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 + T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

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.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Most important contributors to its development are diet and obesity. Gut microbiome's importance for immune system and inflammatory pathways more widely accepted as an important component in NAFLD and other liver diseases' pathogenesis. In this article we review potential mechanisms of microbiome alteration of local and systemic immune responses leading to NAFLD's development, and how can modulate them for the treatment. Our review mentions different immune system pathways and microorganisms regulating metabolism, liver inflammation and fibrosis. We specifically point out TLR-4 as a potential key immune pathway activated by bacterial lipopolysaccharides producing pro-inflammatory cytokines in NAFLD. Also, we discuss three endotoxin-producing strains (Enterobacter cloacae B29, Escherichia coli PY102, Klebsiella pneumoniae A7) that can promote NAFLD development via TLR4-dependent immune response activation in animal models and how they potentially contribute to disease progression in humans. Additionally, we discuss their other immune and non-immune mechanisms contributing to NAFLD pathogenesis. In the end we point out gut microbiome researches' future perspective in NAFLD as a potential new target for both diagnostic and treatment.

Objective: To systematically evaluate the efficacy of intestinal microbiome-targeted therapies (MTTs) in alcohol-related liver disease (ALD). Methods: With pre-specified keywords and strategies, we searched databases including Cochrane Library, PubMed, EMBASE, CNKI, Wanfang Data, and Weipu for RCTs on intestinal MTTs in ALD patients from January 2000 to May 2021. Two researchers independently conducted literature screening, data extraction, and quality evaluation according to the eligible criteria. Outcomes of interest included the effects of intestinal MTTs on ALT, AST, GGT, TBIL, TNF-α, IL-6, intestinal Escherichia coli, and Bifidobacteria when compared to the control group. Pooled data were compiled and analyzed with Revman 5.4 software. Results: Among 5 RCTs included with 456 ALD patients who received probiotics, the therapeutic pooled effects in the experimental group were the followings: ALT (MD = -7.16.95% CI: 10.71∼-3.60; p < 0.0001)、AST (MD = -25.11.95% CI: 30.57∼-19.47; p < 0.00001)、GGT (MD = -6.72.95% CI: 11.91∼-1.53; p = 0.01)、IL-6(SMD = -0.82.95% CI: 1.10∼-0.54; p < 0.00001), which were significantly better than those in the placebo or standard treatment group respectively, while the difference of TBIL (SMD = -0.06, 95%CI: 0.29-0.16; p = 0.59), TNF-α(SMD = -0.53.95% CI: 1.57-0.50; p = 0.31)in the two groups was not significant. After intestinal MTT treatment, the number of intestinal Bifidobacteria increased significantly (MD = 0.79.95% CI: 0.00-1.58; p = 0.05)in the experimental group. However, there were no significant changes in the number of E. coli in both groups (SMD = -0.29.95% CI: 0.92-0.34; p = 0.36). Conclusion: Intestinal MTTs can significantly improve liver function, associated with the increase of intestinal Bifidobacteria, which may be beneficial to ALD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246067, Identifier CRD42021246067.

Diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.

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.

Current evidence indicates a rising global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), which is closely associated to conditions such as obesity, dyslipidemia, insulin resistance, and metabolic syndrome. The relationship between the gut microbiome and metabolites in NAFLD is gaining attention understanding the pathogenesis and progression of dysregulated lipid metabolism and inflammation. The Xie Zhuo Tiao Zhi (XZTZ) decoction has been employed in clinical practice for alleviating hyperlipidemia and symptoms related to metabolic disorders. However, the pharmacological mechanisms underlying the effects of XZTZ remain to be elucidated.

The objective of this study was to examine the pharmacological mechanisms underlying the hypolipidemic and anti-inflammatory effects of XZTZ decoction in a mouse model of NAFLD, as well as the effects of supplementing exogenous metabolites on PO induced cell damage and lipid accumulation in cultured hepatocytes.

A high-fat diet (HFD) mouse model was established to examine the effects of XZTZ through oral gavage. The general condition of mice and the protective effect of XZTZ on liver injury were evaluated using histological and biochemical methods. Hematoxylin and eosin staining (H&E) staining and oil red O staining were performed to assess inflammatory and lipid accumulation detection, and cytokine levels were quantitatively analyzed. Additionally, the study included full-length 16S rRNA sequencing, liver transcriptome analysis, and non-targeted metabolomics analysis to investigate the relationship among intestinal microbiome, liver metabolic function, and XZTZ decoction.

XZTZ had a significant impact on the microbial community structure in NAFLD mice. Notably, the abundance of Ileibacterium valens, which was significantly enriched by XZTZ, exhibited a negative correlation with liver injury biomarkers such as, alanine transaminase (ALT) and aspartate transaminase (AST) activity. Moreover, treatment with XZTZ led to a significant enrichment of the purine metabolism pathway in liver tissue metabolites, with inosine, a purine metabolite, showing a significant positive correlation with the abundance of I. valens. XZTZ and inosine also significantly enhanced fatty acid β-oxidation, which led to a reduction in the expression of pro-inflammatory cytokines and the inhibition of liver pyroptosis. These effects contributed to the mitigation of liver injury and hepatocyte damage, both in vivo and vitro. Furthermore, the utilization of HPLC fingerprints and UPLC-Q-TOF-MS elucidated the principal constituents within the XZTZ decoction, including naringin, neohesperidin, atractylenolide III, 23-o-Acetylalisol B, pachymic acid, and ursolic acid which are likely responsible for its therapeutic efficacy. Further investigations are imperative to fully uncover and validate the pharmacodynamic mechanisms underlying these observations.

The administration of XZTZ decoction demonstrates a protective effect on the livers of NAFLD mice by inhibiting lipid accumulation and reducing hepatocyte inflammatory damage. This protective effect is mediated by the upregulation of I.valens abundance in the intestine, highlighting the importance of the gut-liver axis. Furthermore, the presesnce of inosine, adenosine, and their derivatives are important in promoting the protective effects of XZTZ. Furthermore, the in vitro approaching, we provide hitherto undocumented evidence indicating that the inosine significantly improves lipid accumulation, inflammatory damage, and pyroptosis in AML12 cells incubated with free fatty acids.

Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.

Liver diseases have long been a prevalent cause of morbidity and mortality, and their development and progression involve multiple vital organs throughout the body. Recent studies on the oral-gut-liver axis have revealed that the oral microbiota is associated with the pathophysiology of chronic liver diseases. Since interventions aimed at regulating oral biological disorders may delay the progress of liver disease, it is crucial to better comprehend this process. Oral bacteria with potential pathogenicity have been extensively studied and are closely related to several types of chronic liver diseases. Therefore, this review will systemically describe the emerging role of oral pathogenic bacteria in common liver diseases, including alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, autoimmune liver diseases (AILD), and liver cancer, and bring in new perspectives for future research.

Metabolic-associated Fatty Liver Disease is one of the outstanding challenges in gastroenterology. The increasing incidence of the disease is undoubtedly connected with the ongoing obesity pandemic. The lack of specific symptoms in the early phases and the grave complications of the disease require an active approach to prompt diagnosis and treatment. Therapeutic lifestyle changes should be introduced in a great majority of patients; but, in many cases, the adherence is not satisfactory. There is a great need for an effective pharmacological therapy for Metabolic-Associated Fatty Liver Disease, especially before the onset of steatohepatitis. Currently, there are no specific recommendations on the selection of drugs to treat liver steatosis and prevent patients from progression toward more advanced stages (steatohepatitis, cirrhosis, and cancer). Therefore, in this Review, we provide data on the clinical efficacy of therapeutic interventions that might improve the course of Metabolic-Associated Fatty Liver Disease. These include the drugs used in the treatment of obesity and hyperlipidemias, as well as affecting the gut microbiota and endocrine system, and other experimental approaches, including functional foods. Finally, we provide advice on the selection of drugs for patients with concomitant Metabolic-Associated Fatty Liver Disease.

Alterations in the gut-liver axis and changes in the gut microbiome are among the risk factors for the pathogenesis of non-alcoholic fatty liver disease (NAFLD). These patients show increased bacterial overgrowth in the small intestine and impaired intestinal permeability. Therefore, therapeutic options such as probiotics or prebiotics have been investigated to modulate intestinal microbiota composition to improve NAFLD. Most in vivo and in vitro probiotic studies have focused on reducing hepatic fat accumulation. The beneficial effects of probiotics on NAFLD have been demonstrated in animal models, and the most widely used microorganisms are those of the Lactobacillus and Bifidobacterium genera. In animal models, probiotics help restore the intestinal microbiota and improve the integrity of the intestinal barrier. This narrative review summarizes published evidence and the likely benefits of probiotics and prebiotics as a therapeutic option for patients with NAFLD.