The growing crisis of antibiotic resistance and the increasing incidence of cancer have prompted the exploration of innovative approaches, such as gene editing and antimicrobial peptides (AMPs). The human microbiome is integral to various aspects of health, disease, and therapeutic development, influencing metabolic pathways, immune function, and pathogen resistance. Recent advances in gene editing technologies, particularly CRISPR (clustered regularly interspaced short palindromic repeats), have opened new avenues for leveraging the microbiome to address complex medical challenges, including combating multidrug-resistant pathogens and cancer. The microbiome plays a crucial role in combating antibiotic resistance by modulating microbial communities, influencing pathogen survival and susceptibility to treatments. This review explores the microbiome's dynamic role in metabolic regulation, its contribution to cancer management, and how AMPs help maintain homeostasis and exhibit emerging anticancer properties, supported by both preclinical findings and clinical evidence. Additionally, CRISPR-based microbiome engineering offers potential to enhance host-microbiome interactions, optimizing therapeutic outcomes. The integration of microbiome metagenomics and proteomics has led to the discovery of novel AMPs with targeted anticancer effects. Innovative strategies, such as engineered probiotics and CRISPR-based microbiome engineering, present exciting prospects for next-generation therapies. Despite these advances, the translation of microbiome-based therapies into clinical settings remains challenging due to ethical, regulatory, and ecological hurdles. This review underscores the transformative potential of microbiome-based interventions, emphasizing the role of personalized medicine in maximizing therapeutic efficacy. Furthermore, we also address critical research gaps, limitations, and future directions, including optimizing AMP stability, delivery, and bioavailability, as well as overcoming the regulatory and ethical challenges in clinical translation.

In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that covers and protects all non-keratinized wet epithelial surfaces. In addition to the surface of organs directly contacting with the external environment such as the eyes, this layer provides protection to the underlying gastrointestinal, respiratory and female reproductive tracts by trapping pathogens, irritants, environmental fine particles and potentially harmful foreign substances. Mucins, the primary structural components of mucus, form structurally different mucus layers at different sites in a process regulated by a variety of factors. Currently, more and more studies have shown that the mucus barrier is not only closely related to various intestinal mucus diseases, but also involved in the occurrence and development of various airway diseases and mucus-related diseases, thus it may become a new target for the treatment of various related diseases in the future. Since the dysfunction of the mucous layer is closely related to various pathological processes, in-depth understanding of its molecular mechanism and physiological role is of great theoretical and practical significance for disease prevention and treatment. Here, we discuss different aspects of the mucus layer by focusing on its chemical composition, synthetic pathways, and some of the characteristics of the mucus layer in physiological and pathological situations.

Non-alcoholic fatty liver disease (NAFLD) is a progressive condition with limited effective treatments. This study investigated the therapeutic effects of Aurantio-obtusin (AO), a bioactive compound from Cassiae Semen, on obesity-associated NAFLD. An obesity-related NAFLD model was established in ApoE -/- mice fed a high-fat diet (HFD) for 24 weeks, with AO administered during the last 16 weeks. Mouse body weight, adipose tissue weights, liver weights, serum lipid levels, hepatic steatosis, inflammatory damage, and colonic tissue barrier integrity were evaluated. Gut microbial communities and serum metabolic profiles were analyzed using 16S rRNA sequencing and untargeted metabolomics. Hepatic lipid metabolism-related gene expression was assessed using molecular biology techniques. AO treatment significantly ameliorated HFD-induced adiposity, hyperlipidemia, and NAFLD symptoms. It preserved intestinal barrier integrity, modulated gut microbial composition by enriching beneficial taxa, and improved serum metabolic profiles. AO favorably adjusted hepatic lipid metabolism by upregulating PPARα and CPT1A while downregulating SREBP1, FASN, and SCD1. Correlation analysis revealed significant associations among gut microbial composition, serum metabolites, and disease indicators. AO's therapeutic benefits in NAFLD might be attributed to its ability to modulate gut microbial community composition and serum metabolic profile, enhance intestinal barrier function, and regulate hepatic lipid metabolism gene expression. AO presents a promising therapeutic agent for obesity-associated NAFLD, warranting further investigation into its potential clinical applications.

Dengue fever, a widespread mosquito-borne viral infection in tropical regions, typically manifests fever and gastrointestinal symptoms, including nausea, vomiting, and diarrhea. However, the human gut microbiota's role in dengue pathogenesis remains incompletely understood. Studies have demonstrated dysbiosis during dengue virus infection, characterized by increased abundance of potentially pathogenic bacteria like Bacteroidaceae and Proteobacteria, particularly during the critical phase. Furthermore, microbial translocation and leaky gut syndrome, characterized by the translocation of intestinal microbial products, have been observed in dengue patients and are associated with hypercytokinemia, plasma leakage, and disease severity. These findings underscore the necessity for an in-depth investigation into the role of human intestinal microbiota as a potential contributing factor in the pathogenesis and progression of dengue. Further research focusing on human intestinal microbiota, leaky gut syndrome, and the potential implications of treatment with oral bacteriotherapy, as previously observed in other viral diseases, is essential to clarify dengue pathology and evaluate new therapeutic strategies.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex metabolic disorder characterized by hepatic lipid accumulation and subsequent inflammation. This condition is closely linked to metabolic syndrome and obesity, with its prevalence rising due to sedentary lifestyles and high-calorie diets. The pathogenesis of MAFLD involves multiple factors, including insulin resistance, lipotoxicity, oxidative stress, and inflammatory responses. The gut microbiota plays a crucial role in MAFLD development, with dysbiosis contributing to liver inflammation through various mechanisms, such as enhanced intestinal permeability and the translocation of bacterial products like lipopolysaccharide (LPS). Microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids, influence hepatic function and immune responses, with potential implications for disease progression. Specific gut microbiome signatures have been identified in MAFLD patients, offering potential diagnostic and therapeutic targets. Moreover, gut-derived toxins, such as endotoxins, lipopolysaccharides, trimethylamine-N-oxide and bacterial metabolites, significantly influence liver damage and inflammation, highlighting the complex interplay between the gut microbiome and hepatic health. This review comprehensively examines the complex interplay between the gut microbiota and MAFLD, focusing on underlying pathogenic mechanisms, potential biomarkers, and emerging microbiome-targeted therapeutic strategies for disease management.

To explore the correlation of dietary index for gut microbiota (DI-GM) with non-alcoholic fatty liver disease (NAFLD).

Data of 6,711 participants were extracted from the National Health and Nutrition Examination Survey (NHANES) during 2007-2018. A weighted logistic regression analysis was employed for assessment of the correlation of DI-GM with NAFLD, and a restricted cubic spline (RCS) analysis was implemented to examine potential non-linear associations. Subgroup analyses were conducted to identify particularly susceptible groups. Additionally, the synergistic effects of different DI-GM components on NAFLD risk was assessed by weighted quantile sum (WQS) regression.

The DI-GM exhibited statistically significant correlation with NAFLD [OR (95%CI):0.91 (0.85, 0.98), p = 0.015]. The results of the RCS analysis indicated a linear correlation of DI-GM and NAFLD (p = 0.810 for non-linearity). Further stratified analyses indicated that the negative correlation of DI-GM with NAFLD were significant and consistent for all subgroups. The results of WQS regression revealed that soybean (27%), refined grains (17%), coffee (16%), and red meat (9%) had the highest contribution weights to NAFLD.

As an important tool for assessment of the influences of diet on gut microbiota, DI-GM is negatively correlated with NAFLD risk factors. Soybean, refined grains, coffee, and red meat are key factors influencing NAFLD. The direct correlation of DI-GM with NAFLD shall be explored and the effectiveness of prevention and treatment of NAFLD shall be evaluated by improving DI-GM scores via dietary interventions.

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.

Liver transplantation, as an effective therapy for patients with liver cancer, plays an important role in improving the quality of life of patients. However, the complexity and trauma of liver transplantation can easily lead to the occurrence of malnutrition in patients, and then increase the risk of postoperative complications, which has aroused widespread clinical attention. Reasonable nutritional support can not only maintain the stability of the body's internal environment, reduce the occurrence of complications, but also promote the recovery of liver and other organ functions. In recent years, with the in-depth understanding of nutritional metabolism after liver transplantation, the application of enteral nutrition and parenteral nutrition in nutritional support after liver transplantation has been increasingly extensive and achieved remarkable results. This paper discusses the effect of early postoperative nutritional intervention on patients with liver cancer and liver transplantation, and combined with its mechanism of action, can better understand the effectiveness of intervention, and provide reference for the development of scientific and reasonable nutritional support programs in clinical practice.

The role of gut microbiota in cancer treatment research is receiving increasing attention. This study aims to evaluate the oral nutritional supplementation combined with probiotics on the liver function and intestinal microflora of lung cancer chemotherapy patients. An evaluation was conducted involving 113 patients with lung cancer, who were given routine hospitalization diet and oral nutrition supplement (ONS). The intervention group received probiotic supplementation, while the control group received placebo. It lasted for 21 days. The primary endpoint was the changes in liver function and intestinal microflora. Secondary endpoints included nutrition and immune status, and blood lipids. Compared with the control group, there were differences in the serum levels of ALT, AST, endotoxin and the amount of gut microbiota in the intervention group (P < 0.05). However, no significant changes were found in nutrition, immune, and the blood lipids status. ONS combined with probiotics could improve the liver function and gut microbiota status of lung cancer chemotherapy patients. We speculate that this may be due to the role of supplementing probiotics in regulating the gut-liver axis.

Metabolic diseases (MD), a series of chronic disorders, severely decrease the quality of life for patients but also cause a heavy economic burden. The ancient Chinese herb Pueraria Radix (PR) plays an important role in curing MD. Up to now, the bioactive compounds found in PR demonstrate effective actions in treating various metabolic disorders. This paper systematically summarizes the recent research advances on the pharmacological activities of PR and its constituents, explains the underlying mechanisms of preventing and treating MD. Besides, phytochemicals, drug delivery systems, clinical application, and safety of PR have been researched, hoping to provide valuable information for the future application, development, and improvement of PR as well as MD treatment. The information about PR was collected from various sources including classic books about Chinese herbal medicine and scientific databases including Web of Science, PubMed, ScienceDirect, Springer, ACS, SCOPUS, CNKI, Google Scholar, X-MOL, and WANFANG using keywords given and terms like pharmacological and phytochemical details of this plant. The chemical constituents isolated and identified from PR, such as isoflavones including puerarin, formononetin, daidzin, daidzein, genistein, and so forth, polysaccharides, alkaloids, starch, and other components have been proved to have the effect of anti-diabetic, anti-obesity, anti-atherosclerotic, anti-osteoporotic, anti-hypertensive, anti-hyperlipidemia, and anti-nonalcoholic fatty liver disease (NAFLD) through PI3K/Akt, Nrf2/HO-1, LOX-1/ROS/Akt/eNOS, ERK1/2-Nrf2, GLP-1R, Caspase, MAPK, NF-κB, and other anti-inflammatory and anti-oxidant signaling pathways. Also, the active contents of PR have been designed as drug delivery systems to improve the therapeutic effects of MD. It provides a preclinical basis for the efficacy of PR as an effective therapeutic agent for the prevention and treatment of MD. Even so, further studies are still needed to enhance bioavailability and expand clinical application.

Imbalance in the gut microbiota is a key factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. The Dietary Index for Gut Microbiota (DI-GM) integrates the potential relationship between diet and gut microbiota diversity. This study aims to investigate the association between DI-GM and the risk of NAFLD and liver fibrosis, providing theoretical support for dietary intervention strategies.

This study utilized data from NHANES 2017-2020, including 6,181 eligible adult participants. The relationship between DI-GM and the risk of NAFLD and liver fibrosis was assessed using DI-GM quartiles, multivariate logistic regression, and restricted cubic spline (RCS) analysis. Subgroup analysis was performed to explore the predictive role of DI-GM in different populations. All analyses were weighted to ensure the representativeness of the results.

DI-GM was negatively associated with the risks of NAFLD and liver fibrosis. As DI-GM scores increased, the risk of NAFLD and liver fibrosis significantly decreased (52.81%, 43.16%, 40.40%, and 31.98%, p < 0.05; 17.52%, 9.04%, 7.21%, and 6.78%, p < 0.05). Multivariate logistic regression analysis revealed that, in the unadjusted model (Model 1), for each unit increase in DI-GM, the risk of NAFLD decreased by 6.9% (OR = 0.931, 95% CI: 0.886-0.979, p < 0.001), while the risk of liver fibrosis decreased by 15.6% (OR = 0.844, 95% CI: 0.757-0.941, p < 0.05). In the quartile analysis, individuals in the highest DI-GM quartile (Q4) had a 58% lower risk of NAFLD compared to those in the lowest quartile (Q1) (OR = 0.42, 95% CI: 0.219-0.806, p < 0.001). The results remained significant even after adjusting for covariates. RCS analysis showed that DI-GM had a nonlinear relationship with the risks of NAFLD and liver fibrosis, with inflection points at scores of 2 and 5, indicating enhanced protective effects.

This study reveals a negative association between DI-GM and the risk of NAFLD and liver fibrosis, highlighting the potential role of healthy dietary patterns in the prevention and management of NAFLD and liver fibrosis through gut microbiota modulation, providing a theoretical basis for dietary interventions.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver diseases worldwide, necessitating urgent novel oral treatments. In this study, β-cell expansion factor A (BefA) was evaluated in a murine NAFLD model induced by high-fat diet (HFD). Our results revealed that BefA significantly reduced body weight (36.58 ± 1.55 g vs. 42.30 ± 1.96 g, p < 0.01), fat mass-to-body weight ratio (0.023 ± 0.019 vs. 0.300 ± 0.019, p < 0.05), liver weight (1.90 ± 0.07 g vs. 2.31 ± 0.21 g, p < 0.05), and liver function parameters (ALT, AST, ALP levels reduced, p < 0.05). Notably, BefA reversed the pathological features of NAFLD, decreasing hepatic steatosis score from 3.67 ± 0.47 to 1.67 ± 0.47 (p < 0.01). Mechanistically, BefA activated the AMPK signaling pathway, resulting in the suppression of lipogenic gene transcription (ACC, FASN, SREBP-1c) and the enhancement of fatty acid oxidation (CPT-1, PPAR-α). However, AMPK inhibitor and broad-spectrum antibiotics significantly attenuated the benefits observed with BefA treatment, increasing body weight, fat-to-body weight ratio, and liver weight (p < 0.05). Similar detrimental effects were also observed in liver function indices and histopathological characteristics. These findings underscore the pivotal role of both gut microbiota modulation and AMPK signaling in BefA's therapeutic efficacy, making it a promising multitargeted approach for NAFLD treatment.

Humans consume large amounts of non-starch polysaccharides(NPs) daily. Some NPs, not absorbed by the body, proceed to the intestines. An increasing number of studies reveal a close relationship between NPs and gut microbiota(GM) that impact the human body. This review not only describes in detail the structures of several common NPs and their effects on GM, but also elucidates the degradation mechanisms of NPs in the intestine. The purpose of this review is to elucidate how NPs interact with GM in the intestine, which can provide valuable information for further studies of NPs.

Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver illness, is characterized by hepatic steatosis. Exercise and probiotics can regulate the gut microbiota to treat NAFLD; however, their combined effects and the mechanisms of gut-liver communication remain unclear. Inconsistent results on probiotic efficacy further warrant investigation. In this study, zebrafish fed a high-fat diet (HFD) for six weeks were subjected to swimming exercise (HFDE), probiotic intervention (HFDP), or a combination of both (HFDEP) for 10 weeks to explore their effects on NAFLD and the corresponding mechanism. The results showed that NAFLD alleviation followed the order HFDEP > HFDE > HFDP. HFDEP and HFDE treatments effectively reduced Body Mass Index (BMI), relative liver weight, liver vacuolation density, lipid droplets in liver sections, triglyceride, free fatty acid, glucose, and pyruvic acid. In contrast, a single probiotic treatment had limited impact, suggesting a complementary role in NAFLD treatment. Glucose and fatty acid metabolism were central to the "gut-liver" axis. The reduced conversion of glucose to pyruvic acid, decreased fatty acid synthesis and esterification, and accelerated fatty acid transformation to CO2 contributed to NAFLD improvement under HFDE and HFDEP treatments. This study provides promising theoretical groundwork for potential prevention and treatment strategies for NAFLD.

The purpose of this article is to present selected food additives as disruptors of normal intestinal homeostasis with a potential impact on the development of metabolic dysfunction-associated steatotic liver disease (MASLD). A comprehensive literature search was conducted in three major electronic databases: PubMed, ScienceDirect, and Google Scholar. MASLD is a prevalent liver condition that is closely related to the global rise in obesity. Its pathogenesis is multifactorial, with genetic, environmental, and metabolic factors playing a key role. The "multiple-hit" hypothesis suggests that a Western-style diet, rich in ultra-processed foods, saturated fats, and food additives, combined with low physical activity, contributes to obesity, which promotes lipid accumulation in the liver. Recent studies underscore the role of impaired intestinal homeostasis in the development of MASLD. Food additives, including preservatives, emulsifiers, and sweeteners, affect gut health and liver function. Selected preservatives inhibit pathogenic microorganisms but disrupt the intestinal microbiota, leading to changes in intestinal permeability and liver dysfunction. Some emulsifiers and thickeners can cause inflammation and alter the gut microbiome, contributing to liver steatosis. Furthermore, the use of sweeteners such as sucralose and aspartame has been linked to changes in liver metabolism and intestinal microbial composition, which in turn promotes metabolic disorders.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is correlated with an increased cardiovascular risk, independent of other traditional risk factors. The mechanisms underlying this pathogenic link are complex yet remain incompletely elucidated. Among these, the most significant are visceral adiposity, low-grade inflammation and oxidative stress, endothelial dysfunction, prothrombotic status, insulin resistance, dyslipidemia and postprandial hyperlipemia, gut dysbiosis, and genetic mutations. Cardiovascular diseases are the leading cause of death in patients with MASLD. These patients have an increased incidence of coronary artery disease, carotid artery disease, structural and functional cardiac abnormalities, and valvulopathies, as well as arrhythmias and cardiac conduction disorders. In this review, we present the latest data on the association between MASLD and cardiovascular risk, focusing on the pathogenic mechanisms that explain the correlation between these two pathologies. Given the high rates of cardiovascular morbidity and mortality among patients with MASLD, we consider it imperative to raise awareness of the risks associated with this condition within the general population. Further research is essential to clarify the mechanisms underlying the increased cardiovascular risk linked to MASLD. This understanding may facilitate the identification of new diagnostic and prognostic biomarkers for these patients, as well as novel therapeutic targets.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, with non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of liver tumorigenesis. Due to the obesity epidemics, the occurrence of NAFLD has significantly increased with nearly 30% prevalence worldwide. HCC often arises in the background of chronic liver disease (CLD), such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked to NAFLD progression and HCC development, with several investigations reporting a crucial role for the gut-liver axis and microbial metabolites in promoting CLD. Moreover, the GM affects liver homeostasis, energy status, and the immune microenvironment, influencing the response to immunotherapy with interesting therapeutic implications. In this review, we summarize the main changes in the GM and derived metabolites (e.g., short-chain fatty acids and bile acids) occurring in HCC patients and influencing NAFLD progression, emphasizing their potential as early diagnostic biomarkers and prognostic tools. We discuss the weight loss effects of diet-based interventions and healthy lifestyles for the treatment of NAFLD patients, highlighting their impact on the restoration of the intestinal barrier and GM structure. We also describe encouraging preclinical findings on the modulation of GM to improve liver functions in CLD, boost the antitumor immune response (e.g., probiotic supplementations or anti-hypercholesterolemic drug treatment), and ultimately delay NAFLD progression to HCC. The development of safe and effective strategies that target the gut-liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered.

Helicobacter pylori (H. pylori) infection is linked to metabolic syndrome and insulin resistance, with the triglyceride-glucose (TyG) index serving as a reliable marker for the latter. This study investigates the association between the TyG index and H. pylori infection. The study utilized cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2000. Participants underwent serologic testing for H. pylori, and the TyG index was calculated from fasting laboratory measurements. Multivariate logistic regression and restricted cubic spline methods were used to assess the association and explore the dose-response relationship. The analysis included 2984 participants. Elevated TyG index values were associated with an increased likelihood of H. pylori infection. The risk of infection rose with higher TyG index quartiles, with the highest quartile showing the most significant increase (OR = 1.54, 95% CI: 1.15-2.07, P = 0.004). A linear relationship between the TyG index and H. pylori infection was demonstrated. The study findings indicate a significant positive association between the TyG index and H. pylori infection. This association highlights the importance of metabolic health in the context of H. pylori infection and suggests that further research is needed to explore the potential implications for health promotion strategies.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver alterations worldwide, being gut microbiota dysbiosis one of the contributing factors to its development. The aim of this research is to compare the potential effects of a viable probiotic (Lactobacillus rhamnosus GG) with those exerted by its heat-inactivated paraprobiotic counterpart in a dietary rodent model of NAFLD. The probiotic administration effectively prevented the hepatic lipid accumulation induced by a high-fat high-fructose diet feeding, as demonstrated by chemical (lower TG content) and histological (lower steatosis grade and lobular inflammation) analyses. This effect was mainly mediated by the downregulation of lipid uptake (FATP2 protein expression) and upregulating liver TG release to bloodstream (MTTP activity) in rats receiving the probiotic. By contrast, the effect of the paraprobiotic preventing diet-induced liver lipid accumulation was milder, and mainly derived from the downregulation of hepatic de novo lipogenesis (SREBP-1c protein expression and FAS activity) and TG assembly (DGAT2 and AQP9 protein expression). The obtained results demonstrate that under these experimental conditions, the effects induced by the administration of viable L. rhamnosus GG preventing liver lipid accumulation in rats fed a diet rich in saturated fat and fructose differ from those induced by its heat-inactivated paraprobiotic counterpart.

Incidence of a number of liver diseases has increased. Gut microbiota serves a role in the pathogenesis of hepatitis, cirrhosis and liver cancer. Gut microbiota is considered 'a new virtual metabolic organ'. The interaction between the gut microbiota and liver is termed the gut‑liver axis. The gut‑liver axis provides a novel research direction for mechanism of liver disease development. The present review discusses the role of the gut‑liver axis and how this can be targeted by novel treatments for common liver diseases.

Metabolic-associated fatty liver disease (MAFLD) is an important public health problem, and the gut microbiota has become a new treatment target for MAFLD. Previously, A. indistinctus, a core gut bacterium, was shown to potentially contribute to the prevention of MAFLD. However, the effect and mechanism of A. indistinctus on MAFLD are still unclear and need to be investigated. This study primarily evaluated whether A. indistinctus can improve gut microbiota disorders and prevent the progression from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) in mice fed a high-fat diet (HFD). First, we observed that A. indistinctus significantly improved lipid metabolism disorders and reduced hepatic inflammation induced by HFD consumption in mice. We found that A. indistinctus improved gut barrier function and inhibited the LPS/TLR4/NF-κB pathway, thereby reducing hepatic inflammation. Moreover, 16S rRNA V3-V4 analyses revealed that A. indistinctus could significantly change the structure of the gut microbiota and increase the abundance of L. johnsonii by promoting its growth. Finally, we showed that L. johnsonii administration significantly improved lipid metabolism disorders and reduced hepatic lipid accumulation induced by HFD consumption in mice. In summary, A. indistinctus administration significantly reduces hepatic inflammation by improving gut barrier function and improves lipid metabolism disorders by promoting the growth of L. johnsonii. Our research improves the understanding of the gut microbiota and provides a basis for future therapeutic use of A. indistinctus.

The purpose of this study was to examine the hepatic bacterial composition and metabolome characteristics of patients with NAFLD using 16S rDNA sequencing and metabolomics. The results of the study revealed substantial differences in hepatic bacterial composition and metabolites between the NAFLD group and the control group. These differences were used to identify potential biomarkers that could be employed to diagnose NAFLD.

Liver tissues from 13 patients in the NAFLD group and 12 patients in the control group were collected for microbiota examination.

The bacterial DNA profiles of the liver were significantly different between NAFLD patients and controls. NAFLD patients exhibited an enrichment of Enterobacterales, Mycobacteriales, Pseudomonadales, Flavobacteriales and Xanthomonadales, Sphingomonadales, Lysobact, which was characterised by a lack of erales. At the genus level, the abundance values of Escherichia-Shigella, Rhodococcus, and Chryseobacterium in the NAFLD group were significantly elevated, while the abundance values of Stenotrophomonas, Lawsonella and Sphingobium were significantly reduced. A total of 402 distinct metabolites were identified between the two groups, with 78 metabolites that were up-regulated and 14 metabolites that were down-regulated. The enrichment of metabolic pathways indicated that linoleic acid metabolism was the most significant contributor to the metabolic differences, and lipid metabolism was substantially differentiated. The hepatic metabolite levels were substantially correlated with the changes in hepatic microflora, as demonstrated by the correlation analysis.

Differences in pathogenesis and host physiological function of NAFLD may be attributed to the hepatic flora and metabolomic characteristics. In the future, this presents new opportunities for the investigation of prospective diagnostic and therapeutic targets for NAFLD.

Although previous studies have established associations between specific gut microbiota (GM) and metabolic dysfunction-associated fatty liver disease (MAFLD), research examining the relationship between functional gastrointestinal symptoms and MAFLD, including advanced fibrosis, remains limited. This study aims to investigate the association between stool consistency, bowel movement frequency (BMF), and the occurrence of MAFLD and advanced fibrosis in U.S. adults.

This population-based study included 9,928 adults from the 2005-2010 National Health and Nutrition Examination Survey (NHANES), with a mean age of 47.19 ± 16.65 years, comprising 47.7% males and 52.3% females. Weighted logistic regression was used to assess the association between stool consistency, BMF, and MAFLD or advanced fibrosis. A linear trend was assessed by treating BMF categories as continuous variables with ordinal values. The dose-response relationship between BMF and MAFLD was analyzed using restricted cubic splines (RCS) regression. Sensitivity and subgroup analyses were performed to confirm the robustness of the findings.

In the RCS regression, no significant nonlinear relationship was observed between BMF and the risk of MAFLD (p-overall < 0.0001; p-nonlinear = 0.0663). The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for MAFLD were 0.82 (95% CI 0.69-0.98), 1.31 (95% CI 1.16-1.46), and 1.50 (95% CI 1.14-1.99) for participants with 3-6 BMs/week, 1-2 BMs/day, and > 2 BMs/day, respectively, compared to those with once/day (p-trend < 0.001). For stool consistency, hard stools were associated with a decreased risk of MAFLD (OR 0.77; 95% CI 0.62-0.95), whereas loose stools increased the risk (OR 1.37; 95% CI 1.05-1.80), relative to normal stools. A significant interaction between BMF and age was observed. No significant associations were found between stool consistency or BMF and advanced liver fibrosis. Sensitivity analyses confirmed the robustness of these findings.

This cross-sectional study demonstrates that a BMF of 3-6 BMs/week and hard stools are associated with a reduced risk of MAFLD, whereas a BMF of more than once/day and loose stools are linked to an increased risk of MAFLD. Moreover, no significant associations were observed between stool consistency, BMF, and advanced fibrosis among individuals diagnosed with MAFLD.

Not applicable.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic metabolic liver diseases worldwide. Perillaldehyde (4-propyl-1-en-2-ylcyclohexene-1-aldehyde, PA) is a terpenoid compound extracted from Perilla, which has effective pharmacological activities such as anti-inflammatory, antidepressant, and anticancer. This study aimed to explore the pharmacological effects of PA in intervening with NAFLD and reveal its potential mechanisms. Firstly, we identified the core targets of PA intervention therapy for NAFLD through network pharmacology and molecular docking techniques. After that, in vitro animal experiments such as H&E and Masson staining, immunofluorescence, immunohistochemistry, and Western blot were conducted to validate the results network effectively pharmacology predicted. Network pharmacology analysis suggested that PPAR-α may be the core target of PA intervention in NAFLD. H&E and Masson staining showed that after low-dose (50 mg/kg) PA administration, there was a noticeable improvement in fat deposition in the livers of NAFLD mice, and liver tissue fibrosis was alleviated. Immunohistochemical and immunofluorescence analysis showed that low dose (50 mg/kg) PA could reduce hepatocyte apoptosis, decrease the content of pro-apoptosis protein Bax, and increase the expression of anti-apoptosis protein Bcl-2 in NAFLD mice. Western blot results confirmed that low-dose (50 mg/kg) PA could increase the expression of PPAR-α and inhibit the expression of NF-κB in NAFLD mice. Our study indicated that PA could enhance the activity of PPAR-α and reduce the level of NF-κB in NAFLD mice, which may positively affect the prevention of NAFLD.

Highly prevalent comorbidities associated with metabolic syndrome, such as abdominal obesity, nonalcoholic fatty liver disease (NAFLD) and insulin-resistance/Type 2 diabetes (IR/T2D) share alterations in gut microbiota composition as a potential triggering factor. Recent studies put the attention in the potential usage of postbiotics (inactivated probiotics) on these metabolic alterations. This review summarizes the current evidence regarding the efficacy of postbiotic administration in both, preclinical and clinical studies, for the management of obesity, NAFLD and IR/T2D. Data from preclinical studies (rodents) suggest that postbiotic administration effectively prevents obesity, whereas clinical studies corroborate these benefits also in overweight/obese subjects receiving inactivated bacteria. As for NAFLD, although preclinical studies indicate that postbiotic administration improves different liver markers, no data obtained in humans have been published so far since all the studies are ongoing clinical trials. Finally, while the administration of inactivated bacteria demonstrated to be a promising approach for the management of IR/T2D in rodents, data from clinical trials indicates that in humans, this approach is more effective on IR than in T2D. In conclusion, the available scientific data indicate that postbiotic administration not only is safer, but also as effective as probiotic administration for the management of obesity associated prevalent metabolic alterations.

Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.

(1) Background: Depression, metabolic alternations, and liver diseases are highly comorbid. Studies have shown that probiotics might be helpful in the treatment of the above-mentioned states. The aim of this secondary analysis was to search for possible predictors of probiotics' efficacy on liver-related outcome measures. (2) Methods: Data from 92 subjects from a randomized clinical trial on the effect of probiotics on depression were analyzed. The shift in liver steatosis and fibrosis indices was assessed in the context of baseline immunometabolic, psychometric, dietary, and intestinal permeability factors. Correlation analysis and linear regression models were used. (3) Results: A total of 30% of the variance of the improvement in the score of the aspartate transferase to platelet ratio index was explained by probiotic use, higher pre-intervention triglycerides, cholesterol, C-reactive protein levels, increased cereal intake, and a lower consumption of sweets. Then, the model of the change in alanine transferase indicated that probiotics were efficient when used by subjects with higher basal levels of intestinal permeability markers. (4) Conclusions: Probiotics being used along with a healthy diet may provide additional benefits, such as decreased cardiovascular risk, for patients with measures consistent with the immunometabolic form of depression. Probiotic augmentation may be useful for liver protection among subjects with a suspected "leaky gut" syndrome. ClinicalTrials.gov: NCT04756544.

Due to the increasing global incidence rate of nonalcoholic steatohepatitis (NASH) combined with the lack of effective treatment methods for this disease, there is an urgent need to find new treatment strategies. The aim of this study was to investigate the efficacy of rifaximin in preventing and treating NASH and the related mechanism.

A NASH model was constructed by feeding male C57BL/6 mice a methionine-choline-deficient (MCD) diet for 4 weeks. Rifaximin was administered for 1 week before MCD diet feeding or during the last week of MCD diet feeding to investigate its preventive or therapeutic effects. Liver pathology, hepatic enzyme levels and metabolic indices were measured to evaluate the effects of rifaximin on NASH. Intestinal barrier integrity was measured via the Ussing chamber system and western blotting. 16S rDNA sequencing was conducted to investigate the fecal microbiota composition. Western blotting was performed to evaluate peroxisome proliferator activated receptor (PPAR)α and PPARγ protein levels.

Rifaximin effectively alleviated MCD diet-induced NASH. The microbiota composition in MCD diet-fed mice was significantly altered, and intestinal barrier integrity was disrupted. Dysbiosis and intestinal barrier dysfunction were reversed by rifaximin. In addition, rifaximin modulated PPARα and PPARγ expression in the liver.

Rifaximin effectively alleviated MCD diet-induced NASH by restoring the gut microbiota and reversing intestinal barrier dysfunction, suggesting that rifaximin treatment is a new approach for preventing and treating NASH.

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.

Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a growing global health concern with significant implications for oncogenesis. This review synthesizes current evidence on the association between MASLD and cancer risk, highlighting its role as a risk factor for both intrahepatic and extrahepatic malignancies. MASLD is increasingly recognized as a major cause of hepatocellular carcinoma (HCC), with its incidence rising in parallel with the prevalence of metabolic dysfunction. Furthermore, MASLD is associated with an elevated risk of various gastrointestinal cancers, including colorectal, esophageal, stomach, and pancreatic cancers. Beyond the digestive tract, evidence suggests that MASLD may also contribute to an increased risk of other cancers such as breast, prostate, thyroid, gynecological, renal and lung cancers. Understanding the mechanisms underlying these associations and the impact of MASLD on cancer risk is crucial for developing targeted screening and prevention strategies.

The gastrointestinal tract is an ecosystem with heterogeneous patterns, distributions, and environments, resulting in different microbial compositions in each gut segment. The relationship between diet and microbiota determines this heterogeneity. Consumption of diets high in fat and carbohydrates (HLHC) is associated with gut dysbiosis, low microbial diversity, and metabolic syndrome (MetS). Functional fiber consumption improves the profile and diversity of the gut microbiota (GM); it stimulates the production of short-chain fatty acids (SCFAs), which act as signaling molecules that maintain the gut barrier integrity and induce hormone synthesis that regulates satiety and glucose metabolism, reducing some MetS parameters. The effect of a dietary intervention with Acanthocereus tetragonus (At), a cactus rich in fiber, antioxidants, amino acids, and minerals traditionally consumed by the Mexican population, is reported here. For this purpose, Wistar rats were randomly divided into three study groups: a control (C) group, a MetS group, and an At-supplemented group. In the MetS and At groups, an HLHC was administered for 12 weeks, inducing MetS. After 18 weeks, stool samples were collected for microbiota sequencing. HLHC administration favored Firmicutes and decreased the abundance of Bacteriodetes at the phylum level in the MetS group. At the genus level, the dietary intervention with At increased the presence of Roseburia, Ruminococcus, Blautia, Bacteroides, and Christensenella, reflecting the effect of A. tetragonus consumption on GM. At diet administration reduced body weight; the plasma glucose, insulin, and lipid levels; and insulin resistance.

The prevalence of pancreatic steatosis has increased and it has been linked to the rising prevalence of metabolic syndrome. Metabolic syndrome is known to have a strong connection with changes in intestinal microbiota. The aim of this study was to explore the relationship between pancreatic steatosis and the levels of trimethylamine N-oxide (TMAO) and butyrate. In this study, 136 individuals were randomly selected from outpatient clinics at Firat University Hospital. The study evaluated their demographic characteristics, anthropometric measurements, and biochemical parameters. The presence of pancreatic steatosis was assessed using abdominal ultrasonography. Additionally, the levels of TMAO and butyrate were measured. The mean age of individuals in the study was 44.5 ± 14.6. 84 of the subjects were females. Using the waist circumference, 61 were considered obese and 34 overweight. The detection rate of pancreatic steatosis was found to be 70.6%. The study found that individuals with steatosis had higher average age, presence of hepatic steatosis, BMI, waist circumference measurements, and presence of metabolic syndrome than those without steatosis. A significantly higher butyrate level was detected in those without steatosis (p = 0.001). TMAO levels were slightly higher in patients without steatosis than in those with steatosis; however, this was insignificant. Pancreatic steatosis is highly associated with alterations in levels of microbiota metabolites, indicating a potential role of these metabolites in the pathogenesis of the disease and subsequent therapeutic targets. Several other factors, such as age, hepatic steatosis, diabetes, and waist circumference, have also been identified as potential predictors of pancreatic steatosis.

Patients with non-alcoholic fatty liver disease (NAFLD) benefit from using synbiotics. However, findings from existing trials remain contentious. Therefore, this meta-analysis evaluated the effects of synbiotics on liver enzymes, blood pressure, inflammation, and lipid profiles in patients with NAFLD.

We searched PubMed, Embase, Cochrane, Scopus, and Web of Science for randomized controlled trials (RCTs) regarding synbiotics supplementation in patients with NAFLD.

The meta-analysis revealed that synbiotics supplementation significantly improved liver enzymes (AST, WMD: -9.12 IU/L; 95 % CI: -13.19 to -5.05; ALT, WMD: -8.53 IU/L; 95 % CI: -15.07 to -1.99; GGT, WMD: -10.42 IU/L; 95 % CI: -15.19 to -5.65), lipid profile (TC, WMD: -7.74 mg/dL; 95 % CI: -12.56 to -2.92), obesity indices (body weight, WMD: -1.95 kg; 95 % CI: -3.69 to -0.22; WC, WMD: -1.40 cm; 95 % CI: -2.71 to -0.10), systolic blood pressure (SBP, WMD: -6.00 mmHg; 95 % CI: -11.52 to -0.49), and inflammatory markers (CRP, WMD: -0.69 mg/L; 95 % CI: -1.17 to -0.21; TNF-α, WMD: -14.01 pg/mL; 95 % CI: -21.81 to -6.20).

Overall, supplementation with synbiotics positively improved liver enzymes, obesity indices, and inflammatory cytokines in patients with NAFLD.

The purpose of this study is to investigate the effects of non-obese MAFLD on the gut microbiota and metabolic pathways caused by high-temperature processed meals. It was decided to divide the eighteen male Sprague-Dawley rats into three groups: the control group, the dry-fried soybeans (DFS) group, and the high-fat diet (HFD) group. Following the passage of twelve weeks, a series of physical, biochemical, histological, and microbiological examinations were carried out. There were distinct pathological abnormalities brought about by each diet. The DFS diet was found to cause the development of fatty liver and to demonstrate strong relationships between components of the gut microbiota, such as Akkermansia and Mucispirillum, and indices of liver health. Diet-induced changes in the gut microbiome have a significant impact on liver pathology in non-obese patients with metabolically altered liver disease (MAFLD), which suggests that dietary interventions that target gut microbiota could be used to manage or prevent the illness.

In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has risen annually, yet due to the intricacies of its pathogenesis and therapeutic challenges, there remains no definitive medication for this condition. This review explores the intricate relationship between the intestinal microbiome and the pathogenesis of NAFLD, emphasizing the substantial roles played by Lactobacillus plantarum and Bifidobacterium bifidum. These probiotics manipulate lipid synthesis genes and phosphorylated proteins through pathways such as the AMPK/Nrf2, LPS-TLR4-NF-κB, AMPKα/PGC-1α, SREBP-1/FAS, and SREBP-1/ACC signaling pathways to reduce hepatic lipid accumulation and oxidative stress, key components of NAFLD progression. By modifying the intestinal microbial composition and abundance, they combat the overgrowth of harmful bacteria, alleviating the inflammatory response precipitated by dysbiosis and bolstering the intestinal mucosal barrier. Furthermore, they participate in cellular immune regulation, including CD4+ T cells and Treg cells, to suppress systemic inflammation. L. plantarum and B. bifidum also modulate lipid metabolism and immune reactions by adjusting gut metabolites, including propionic and butyric acids, which inhibit liver inflammation and fat deposition. The capacity of probiotics to modulate lipid metabolism, immune responses, and gut microbiota presents an innovative therapeutic strategy. With a global increase in NAFLD prevalence, these insights propose a promising natural method to decelerate disease progression, avert liver damage, and tackle associated metabolic issues, significantly advancing microbiome-focused treatments for NAFLD.

The prevalence of the world's second leading neurodegenerative disorder Parkinson's disease (PD) is well known while its pathogenesis is still a topical issue to explore. Clinical and experimental reports suggest the prevalence of disturbed gut microflora in PD subjects, with an abundance of especially Gram-negative bacteria. The endotoxin lipopolysaccharide (LPS) released from the outer cell layer of these bacteria interacts with the toll-like receptor 4 (TLR4) present on the macrophages and it stimulates the downstream inflammatory cascade in both the gut and brain. Recent research also suggests a positive correlation between LPS, alpha-synuclein, and TLR4 levels, which indicates the contribution of a parallel LPS-alpha-synuclein-TLR4 axis in stimulating inflammation and neurodegeneration in the gut and brain, establishing a body-first type of PD. However, owing to the novelty of this paradigm, further investigation is mandatory. Modulating LPS biosynthesis and LPS-TLR4 interaction can ameliorate gut dysbiosis and PD. Several synthetic LpxC (UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase; LPS-synthesizing enzyme) inhibitors and TLR4 antagonists are reported to show beneficial effects including neuroprotection in PD models, however, are not devoid of side effects. Plant-derived compounds have been long documented for their benefits as nutraceuticals and thus to search for effective, safer, and multitarget therapeutics, the present study focused on summarizing the evidence reporting the potential of phyto-compounds as LpxC inhibitors and TLR4 antagonists. Studies demonstrating the dual potential of phyto-compounds as the modulators of LpxC and TLR4 have not yet been reported. Also, very few preliminary studies have reported LpxC inhibition by phyto-compounds. Nevertheless, remarkable neuroprotection along with TLR4 antagonism has been shown by curcumin and juglanin in PD models. The present review thus provides a wide look at the research progressed to date in discovering phyto-compounds that can serve as LpxC inhibitors and TLR4 antagonists. The study further recommends the need for expanding the search for potential candidates that can render dual protection by inhibiting both the biosynthesis and TLR4 interaction of LPS. Such multitarget therapeutic intervention is believed to bring fruitful yields in countering gut dysbiosis, neuroinflammation, and dopaminergic neuron damage in PD patients through a single treatment paradigm.

Cirrhosis, a pathological stage that develops from various chronic liver diseases, is characterized by liver fibrosis, pseudolobular formation, and chronic inflammation. When it progresses to the decompensated phase, the mortality rate of cirrhosis can reach 80%. The role of gut microbiota in the progression of liver diseases has received significant attention. Numerous studies have shown that regulating gut microbiota has significant therapeutic effects on preventing and reversing liver cirrhosis. This article reviewed the mechanisms by which gut microbiota influence liver cirrhosis, explaining the effective therapeutic effects of traditional Chinese medicine. Through multi-directional regulation involving signaling pathways, gut microbiota diversity, and restoration of intestinal barrier function, traditional Chinese medicine has been promising in ameliorating liver cirrhosis, providing treatment options and pharmacological guidance for the occurrence and development of liver cirrhosis.

The preservation of the Lingguizhugan (LGZG) decoction and patient compliance issue often limit the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Hence, herein, an LGZG oral solution was developed for alleviating MASLD. Additionally, the potential mechanisms underlying LGZG-mediated MASLD mitigation were explored.

A MASLD mouse model was constructed using oleic and palmitic acid-induced LO2 cells and a high-fat diet. The apoptosis, lipid deposition, and mouse liver function were analyzed to assess the therapeutic effects of the LGZG oral solution on MASLD. Serum untargeted metabolomics, gut microbiota, bile acid (BA) metabolism, immunohistochemistry, and Western blotting analyses were performed to investigate the potential mechanism of action of LGZG oral solution on MASLD.

The LGZG oral solution ameliorated lipid deposition, oxidative stress, inflammation, and pathological damage. Serum untargeted metabolomics results revealed the LGZG-mediated regulation of the primary BA biosynthetic pathway. The 16S ribosomal RNA sequencing of the fecal microbiota showed that LGZG oral solution increased the relative abundance of the BA metabolism-associated Bacteroides, Akkermansia, and decreased that of Lactobacillus. Additionally, the BA metabolism analysis results revealed a decrease in the total taurine-α/β-muricholic acid levels, whereas those of deoxycholic acid were increased, which activated specific receptors in the liver and ileum, including farnesoid X receptor (FXR) and takeda G protein-coupled receptor 5 (TGR5). Activation of FXR resulted in an increase in short heterodimer partner and subsequent inhibition of cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, and activation of FXR also results in the upregulation of fibroblast growth factor 15/19 expression, and consequently inhibition of cholesterol 7α-hydroxylase, which correlated with hepatic BA synthesis and lipogenesis, ultimately attenuating lipid deposition and bile acid stasis, thereby improving MASLD.

Altogether, the findings of this study suggest that modulating microbiota-BA-FXR/TGR5 signaling pathway may be a potential mechanism of action of LGZG oral solution for the treatment of MASLD.

Nonalcoholic fatty liver disease (NAFLD) is a mainstream halting liver disease with high prevalence in North America, Europe, and other world regions. It is an advanced form of NAFLD caused by the amassing of fat in the liver and can progress to the more severe form known as non-alcoholic steatohepatitis (NASH). Until recently, there was no authorized pharmacotherapy reported for NASH, and to improve the patient's metabolic syndrome, the focus is mainly on lifestyle modification, weight loss, ensuring a healthy diet, and increased physical activity; however, the recent approval of Rezdiffra (Resmetirom) by the US FDA may change this narrative. As per the reported studies, there is an increased articulation of uptake and efflux transporters of the liver, including OATP and MRP, in NASH, leading to changes in the drug's pharmacokinetic properties. This increase leads to alterations in the pharmacokinetic properties of drugs. Furthermore, modifications in Cytochrome P450 (CYP) enzymes can have a significant impact on these properties. Xenobiotics are metabolized primarily in the liver and constitute liver enzymes and transporters. This review aims to delve into the role of metabolism, transport, and potential herb-drug interactions in the context of NASH.