The Role of the Gut-Liver Axis in Metabolic Dysfunction-Associated Fatty Liver Disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Martin-Mateos R
PROVIDER: S-EPMC8085382 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of A. muciniphila in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with A. muciniphila efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. Together, these data indicate that the anti-MAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut-liver interactions through regulating the metabolism of L-aspartate. A. muciniphila could be a potential agent for clinical intervention in MAFLD.
| S-EPMC8158032 | biostudies-literature
Project description:Metabolic-dysfunction-associated fatty liver disease (MAFLD) is the recent nomenclature designation that associates the condition of non-alcoholic fatty liver disease (NAFLD) with metabolic dysfunction. Its diagnosis has been debated in the recent period and is generally associated with a diagnosis of steatosis and at least one pathologic condition among overweight/obesity, type 2 diabetes mellitus, and metabolic dysregulation. Its pathogenesis is defined by a "multiple-hit" model and is associated with alteration or dysbiosis of the gut microbiota. The pathogenic role of dysbiosis of the gut microbiota has been investigated in many diseases, including obesity, type 2 diabetes mellitus, and NAFLD. However, only a few works correlate it with MAFLD, although common pathogenetic links to these diseases are suspected. This review underlines the most recurrent changes in the gut microbiota of patients with MAFLD, while also evidencing possible pathogenetic links.
| S-EPMC10054528 | biostudies-literature
Project description:Background/aimsMetabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed.MethodsThis retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term.ResultsThis study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD.ConclusionsCombined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.
| S-EPMC9289825 | biostudies-literature
Project description:Background and aimsWe compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD.MethodsIn this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of anthropometric parameters, biochemical variables, liver ultrasonography, and spirometry. The severity of liver disease was assessed by the fibrosis (FIB)-4 score.ResultsThe prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alcohol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was diminished by 0.507 (95% CI: -0.840, -0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: -0.739, -0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women.ConclusionsMAFLD was significantly associated with a greater impairment of lung function parameters than NAFLD.
| S-EPMC9039714 | biostudies-literature
Project description:Metabolic dysfunction-associated fatty liver disease (MAFLD) is a phenotype of liver diseases associated with metabolic syndrome. The pathogenesis MAFLD remains unclear. The liver maintains is located near the intestine and is physiologically interdependent with the intestine via metabolic exchange and microbial transmission, underpinning the recently proposed "oral-gut-liver axis" concept. However, little is known about the roles of commensal fungi in the disease development. This study aimed to characterize the alterations of oral and gut mycobiota and their roles in MAFLD. Twenty-one MAFLD participants and 20 healthy controls were enrolled. Metagenomics analyses of saliva, supragingival plaques, and feces revealed significant alterations in the gut fungal composition of MAFLD patients. Although no statistical difference was evident in the oral mycobiome diversity within MAFLD and healthy group, significantly decreased diversities were observed in fecal samples of MAFLD patients. The relative abundance of one salivary species, five supragingival species, and seven fecal species was significantly altered in MAFLD patients. Twenty-two salivary, 23 supragingival, and 22 fecal species were associated with clinical parameters. Concerning the different functions of fungal species, pathways involved in metabolic pathways, biosynthesis of secondary metabolites, microbial metabolism in diverse environments, and carbon metabolism were abundant both in the oral and gut mycobiomes. Moreover, different fungal contributions in core functions were observed between MAFLD patients and the healthy controls, especially in the supragingival plaque and fecal samples. Finally, correlation analysis between oral/gut mycobiome and clinical parameters identified correlations of certain fungal species in both oral and gut niches. Particularly, Mucor ambiguus, which was abundant both in saliva and feces, was positively correlated with body mass index, total cholesterol, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase, providing evidence of a possible "oral-gut-liver" axis. The findings illustrate the potential correlation between core mycobiome and the development of MAFLD and could propose potential therapeutic strategies.
| S-EPMC10170973 | biostudies-literature
Project description:Background and aimsDisease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease (MAFLD) remains elusive. This study assessed the fibrosis stages and features of MAFLD between different items. We also aimed to investigate the associations between advanced fibrosis and risk factors.MethodsThis multicenter cross-sectional study enrolled adults participating in liver disease screening in the community. Patients were stratified following MAFLD diagnostic criteria, to group A (395 patients) for type 2 diabetes, group B (1,818 patients) for body mass index (BMI)>23 kg/m2, and group C (44 patients) for BMI≤23 kg/m2 with at least two metabolic factors. Advanced fibrosis was defined as a fibrosis-4 index>2.67.ResultsBetween 2009 and 2020, 1,948 MAFLD patients were recruited, including 478 with concomitant liver diseases. Advanced fibrosis was observed in 125 patients. A significantly larger proportion of patients in group C (25.0%) than in group A (7.6%) and group B (5.8%) had advanced fibrosis (p<0.01). Logistic regression analysis found that hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection (odds ratio [OR]: 12.14, 95% confidence interval [CI]: 4.04-36.52; p<0.01), HCV infection (OR: 7.87, 95% CI: 4.78-12.97; p<0.01), group C (OR: 6.00, 95% CI: 2.53-14.22; p<0.01), and TC/LDL-C (OR: 1.21, 95% CI: 1.06-1.38; p<0.01) were significant predictors of advanced fibrosis.ConclusionsA higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis. HCV infection was significantly associated with advanced fibrosis.
| S-EPMC10412709 | biostudies-literature
Project description:The prevalence of metabolic risk factors and non-alcoholic fatty liver disease (NAFLD) is high among people living with HIV (PLWH). Data on the recently proposed definition of metabolic dysfunction-associated fatty liver disease (MAFLD) in PLWH receiving antiretroviral therapy (ART) remains unknown. A total of 282 PLWH were included in this cross-sectional cohort study. Vibration-controlled transient elastography (VCTE) was used to assess hepatic steatosis and fibrosis. MAFLD and its subgroups (overweight/obese, lean/normal weight, and type 2 diabetes) were defined according to a recently published international consensus statement. The majority of this cohort was male (n = 198, 70.2%), and the median age was 51.5 years. The median BMI was 25 kg/m2, and obesity was prevalent in 16.2% (n = 44). A total of 207 (73.4%) PLWH were classified as non-MAFLD while 75 (26.6%) qualified as MAFLD. The median CAP in the MAFLD group was 320 dB/m. PLWH with MAFLD showed a higher median LSM (p < 0.008) and were older (p < 0.005) compared to the non-MAFLD group. Overall, the metabolic risk profile was comparable between MAFLD and NAFLD. The majority of PLWH and MAFLD were overweight or obese (n = 58, 77.3%). The highest median LSM values were observed in the subgroup with MAFLD and type 2 diabetes. HIV-related parameters did not differ between non-MAFLD and MAFLD. The prevalence of MAFLD in PLWH is high and comparable to NAFLD. PLWH may be characterized according to the novel MAFLD criteria and its subgroups to identify patients at risk for chronic liver disease.
| S-EPMC10244325 | biostudies-literature
Project description:IntroductionWe aimed to confirm the association between some single nucleotide polymorphisms (SNPs) and metabolic dysfunction-associated fatty liver disease (MAFLD) in western China.MethodsA total of 286 cases and 250 healthy controls were enrolled in our study. All samples were genotyped for patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, membrane-bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, glucokinase regulator (GCKR) rs1260326 and rs780094, and GATA zinc finger domain containing 2A (GATAD2A) rs4808199. Using logistic regression analysis, we evaluated the association between MAFLD and each SNP under different models. Multiple linear regression was used to find the association between SNPs and laboratory characteristics. Multifactor dimensionality reduction was applied to test SNP-SNP interactions.ResultsThe recessive model and additive model of PNPLA3 rs738409 variant were related to MAFLD (odds ratio [OR] = 1.791 and 1.377, respectively, p = 0.038 and 0.027, respectively). However, after Benjamini-Hochberg adjustment for multiple tests, all associations were no longer statistically significant. PNPLA3 rs738409 correlated with AST levels. GCKR rs780094 and rs1260326 negatively correlated with serum glucose but positively correlated with triglycerides in MAFLD. Based on MDR analysis, the best single-locus and multilocus models for MAFLD risk were rs738409 and six-locus models, respectively.ConclusionsIn the Han population in western China, no association was found between these SNPs and the risk of MAFLD. PNPLA3 rs738409 was associated with aspartate aminotransferase levels in MAFLD patients. GCKR variants were associated with increased triglyceride levels and reduced serum fasting glucose in patients with MAFLD.
| S-EPMC9459258 | biostudies-literature
Project description:Background/aimsWe investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study.MethodsIndividuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m2), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis.ResultsAmong 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85).ConclusionsMAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.
| S-EPMC9099391 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) has recently become the most common liver disease with a global prevalence of over 25% and is expected to increase. Recently, experts have reached a consensus that "fatty liver disease associated with metabolic dysfunction or MAFLD" may be a more appropriate and inclusive definition than NAFLD. Like the former name NAFLD, MAFLD, as a manifestation of multiple system metabolic disorders involving the liver, has certain heterogeneity in its pathogenesis, clinical manifestations, pathological changes and natural outcomes. We found that there is a delicate dynamic balance among intestinal microflora, metabolites and host immune system to maintain a healthy intestinal environment and host health. On the contrary, this imbalance is related to diseases such as MAFLD. However, there are no clear studies on how dietary nutrients affect the intestinal environment and participate in the pathogenesis of MAFLD. This review summarizes the interactions among dietary nutrients, intestinal microbiota and MAFLD in an attempt to provide evidence for the use of dietary supplements to regulate liver function in patients with MAFLD. These dietary nutrients influence the development and progression of MAFLD mainly through the hepatic-intestinal axis by altering dietary energy absorption, regulating bile acid metabolism, changing intestinal permeability and producing ethanol. Meanwhile, the nutrients have the ability to combat MAFLD in terms of enriching abundance of intestinal microbiota, reducing Firmicutes/Bacteroidetes ratio and promoting abundance of beneficial gut microbes. Therefore, family therapy with MAFLD using a reasonable diet could be considered.
| S-EPMC9247350 | biostudies-literature