Disease ⇒ Steatohepatitis ⇒ Metabolic associated fatty liver disease {40000151} Record Keys Type:Disease Parent:Steatohepatitis Definition:Metabolic associated fatty liver disease Details Initialisation date:2020-09-06 Other Terms:NAFLD, NAFLD,Non-alcoholic fatty liver disease LinksWickipediaMerck Manual Meta Information MedDra ID:10082249 MedDra Level:pt ICD:[ ] Category:Gastroenterology Zone:[ ] Mechanism:[ ] Notes: - Low levels of Parabacteroides distasonis lead to the development of NASH and increase cardiovascular risk. (1) - Decreased levels of Prevotella might be detrimental for adults with NAFLD. (2)Shared Reference Notes [1.1] - Metagenome-based gut microbiome panel can accurately diagnose advanced fibrosis [1.2] - Butyrate-producing bacteria were decreased and ethanol-producing bacteria were increased in patients with NAFLD. [1.3] [#Exercise training] -The exercise group showed improvements in the clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. - Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. - Analysis of the microbial composition revealed that the numbers of Campylobacter, Corynebacterium, Actinomyces , and Lautropia were significantly higher, and that of Prevotella was significantly lower. [1.4] - Some #Bacteroides species have been reported to be protective against MAFLD [1.5] -The family #Ruminococcaceae has been consistently reported as less abundant in NAFLD [1.6] - Patients with NAFLD/NASH exhibit > increased numbers of Bacteroidetes and differences in the presence of Firmicutes > resulting in a decreased F/B ratio. - They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. - Patients with NASH show > a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. - Children with NAFLD/NASH have a > decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. - Various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. [1.7] [1.8] [#Spinach consumption] [1.9] - NAFLD patients have the high abundance of Bradyrhizobium, Anaerococcus, Peptoniphilus, Propionibacterium acnes, Dorea, and Ruminococcus, with the low abundance of Oscillospira and Rikenellaceae. - In a Chinese cohort, the genera Lactobacillus, Oscillibacter, and Ruminiclostridium have been found to be decreased in obese NAFLD patients, while Faecalibacterium prausnitzii was the only species that presents a different abundance between those with and without NAFLD. - For the women cohort, the abundance of several different genera such as Subdoligranulum, Coprococcus, and Coprobacter were negatively correlated with hepatic steatosis - Fatty Liver > increased N, N, N-trimethyl-#5-aminovaleric acid [#Short Chain Fatty Acid] - SCFAs are considered to be able to alleviate the development of nonalcoholic fatty liver diseases (NAFLD), which may derive from their potential contribution to regulating fatty acid oxidation, inflammation, and insulin resistance. [1.11] - When translating these taxonomic shifts into predictive metabolic alterations, namely putative changes on microbial metabolic pathways, results suggested that the consortium was predicted to increase the biosynthesis of BCAA, and to decrease the biosynthesis of AAA and methionine. This is an interesting result, because a decreased BCAA/AAA ratio has been shown to correlate with liver dysfunction in cirrhotic patients. - BCAA treatment was shown to ameliorate liver fat accumulation in experimental animal models via increased production of acetic acid by gut microbes [1.12] [#Metabolic Dysfunction-associated Steatohepatitis] [#Lipopolysaccharide, #TMA] - A shift in the metabolic function of intestinal bacteria is predominantly caused by dysbiosis. In the intestine, it leads to an increase in the permeability of intestinal mucosa for LPS and ultimately causes chronic inflammation. Concentration of bacterial metabolites in the blood, such as trimethylamine which is metabolized in the liver to trimethylamine-N-oxide (#TMAO) correlates with the severity of #Steatohepatitis [1.13] - #Exiguobacterium acetylicum leads to increased lipid accumulation in the liver, [1.14] [#Short Chain Fatty Acid] - SCFA levels were observed to be decreased in non-obese non-alcoholic fatty liver disease. - SCFAs help to inhibit the progress of NAFLD in a variety of ways. - As histone deacetylase inhibitors, #Propionate, #Acetate, and #Butyrate play an important role in NAFLD by decreasing chromatin-bound acetyl groups [1.15] [#Metabolic Dysfunction-associated Steatohepatitis] [1.16] - patients with NAFLD had higher rates of #Dementia and vascular #Dementia. - Comorbid NAFLD and either heart disease or stroke conferred a greater risk of #Dementia. [1.17] [#Metabolic Dysfunction-associated Steatohepatitis] - median portal vein #Ethanol concentrations were 187 (interquartile range (IQR), 17–516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. - Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood #Ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. - #Lactobacillaceae correlated with postprandial peripheral #Ethanol concentrations. [1.18] - Via disturbing intestinal metabolic and immune pathways, #Porphyromonas gingivalis accelerates the progression of non-alcoholic fatty liver disease [#Prevotella intermedia] - in mice experiments, oral administration of P. intermedia induces NAFLD [1.19] [#Alcohol Consumption, #Bacteriophage] - high alcohol-producing #Klebsiella pneumoniae (HiAlc Kpn) in the intestinal microbiome could be one of the causes of non-alcoholic fatty liver disease (NAFLD). - treatment with HiAlc Kpn-specific phage was able to alleviate steatohepatitis caused by HiAlc Kpn, including hepatic dysfunction and expression of cytokines and lipogenic genes. - An increase in #Dorea, combined with decreases in #Alistipes appears to be characteristic of MAFLD patients. - #Ruminococcus obeum and #Alistipes were most enriched in healthy individuals when compared with MAFLD patients. - In MAFLD > #Alistipes has negatively related to serum #Glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). - the abundance of #Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. - #Dorea, #Lactobacillus and #Megasphaera are enriched in MAFLD group. [1.21] [#Ruminococcaceae] - #Coriobacteriia, #Actinomycetales, #Oxalobacteraceae, Ruminococcaceae_UCG005 are positively associated with non-alcoholic fatty liver disease. - #Christensenellaceae, and #Intestinibacter were negatively correlated with non-alcoholic fatty liver disease. [1.22] [#Diabetes Type 2] - #Kombucha > improve glycemic parameters, including #Glucose tolerance, and attenuate symptoms associated with nonalcoholic fatty liver disease in obese mice. [1.23] - #Bile Acids may participate in the regulation of gene transcription because they are endogenous ligands for the nuclear receptor Farnesoid X receptor (FXR). - FXR agonists have been used to treat nonalcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids - #Lactobacillus oris treatment increased the expressions of both FXR and SREBP-2 in the liver of mice, suggesting that it might improve NAFLD through the FXR and SREBP pathways. - both intestine ASBT and liver CYP7A were reduced by #Lactobacillus oris, [1.24] [#Inflamatory bowel disease] - #Ruminococcus gnavus, which is a mucin-degrading group, in inflammatory bowel disease and in altered lipid metabolism related to non-alcoholic fatty liver disease (NAFLD) and #Obesity [1.25] [#Metabolic Dysfunction-associated Steatohepatitis] [1.26] - #Lactobacillus may be used as a #Probiotic to improve #Steatohepatitis through the gut microbiota–liver axis by modulating gut microbiota composition and the inflammatory pathway in NAFLD [#Metabolic Dysfunction-associated Steatohepatitis] [#Lipopolysaccharide] - The elevated localization of LPS in hepatocytes has been reported in NAFLD and may cause liver inflammation via a TLR4-related pathway. - LPS is a risk factor for inducing hepatic inflammation and NASH. - The upregulation of the LPS-TLR4 pathway leads to NF-κB activation and inflammatory cytokine production, which play key roles in NASH progression and development [1.27] [#Chronic liver disease] [#Bacteroides stercoris] [#Resistant starch] - RS reduced the abundance in the gut of B. stercoris, which is one of the species highly correlated with IHTC, ALT, and AST. - positive association of B. stercoris in the gut with NAFLD [#Fibroblast growth factor 21] [#Resistant starch] - The serum level of FGF21 was found to be significantly reduced after the 4-month RS intervention. - FGF21 > alleviation of #Dyslipidemia and NAFLD. - circulating FGF21 is paradoxically elevated in individuals with NAFLD > FGF21 resistance in analogy to obesity-associated insulin and leptin resistance. - aberrant FGF21 signaling has been suggested as a key pathological step in the development and progression of NAFLD. [#Liver fibrosis] [#Bacteroides stercoris] - B. stercoris was selected as a feature in a metagenome-based model for predicting advanced fibrosis in US patients with NAFLD. [#Obesity] [#Fibroblast growth factor 21] - both circulating and hepatic levels of FGF21 in obese mice were markedly reduced by #Exercise training, where the FGF21 sensitivity in adipose tissue was enhanced. [#Bacteroides stercoris] [#Branched-chain amino acids] - higher hepatic lipid accumulation was only observed in the mice gavaged with live B. stercoris, which was accompanied by the significantly higher levels of fecal BCAAs. [#Bacteroides stercoris] [#Branched-chain amino acids] - the abundance of B. stercoris in human participants was also found to positively correlate with BCAAs (statistically significant for #Valine), and targeted measures of BCAAs in the monoculture supernatant of live B. stercoris substantiated its BCAA-releasing activity. [#Branched-chain amino acids] [#Fecal Microbiota Transplantation, #Resistant starch] - FMT > transfer of RS-altered microbiota into mice alleviated NAFLD, the colonic levels of BCAAs were also decreased [#Fibroblast growth factor 21] [#Resistant starch] - decreased serum level of FGF21 in participants after RS intervention and in mice receiving feces from RS-fed donors,. - increased expression of its receptor complex and downstream effector in adipose tissue. [#Metabolic Dysfunction-associated Steatohepatitis] [#Branched-chain amino acids] [#Resistant starch] - 4-month RS intervention in humans could significantly reduce the serum levels of BCAAs. - serum BCAAs were positively correlated with IHTC, ALT, AST, and GGT > direct influence of BCAAs on hepatic steatosis and thus NAFLD pathogenesis. [1.28] [#Diabetes Type 2, #Hepatocellular cancer] - Among people with NAFLD, the presence of type 2 diabetes is associated with a significantly higher risk of hepatic decompensation and hepatocellular carcinoma. [1.29] [#Diabetes Type 2] [#Meat-based diet] - Consumption of processed meat, red meat, soda, biscuits, and cakes has been linked to insulin resistance and NAFLD. - #Betaine, #Choline, #Betaine, #Folate, and #Vitamin B12 deficiencies may promote DNA methylation, boosting hepatic #Triglyceride production. [#Gender, #High fibre diet] - Consumption of #Nuts, seeds, seafood, and high-fiber diets considerably reduces the risk of developing NAFLD in males. [#Metabolic Dysfunction-associated Steatohepatitis] [#Coffee, #High fibre diet, #Mediterranean diet] [#Xanthohumol] - XN also exhibits hepatoprotective effects in animal models of MAFLD and other liver-damaging conditions [1.31] [#Autism, #Metabolic Dysfunction-associated Steatohepatitis] - #Methyl isobutyl ketone, the highest ketone associated with ASD, we assume that its presence probably derived from the gut microbial imbalance of patients. This metabolite has also been described for nonalcoholic fatty liver disease (NAFLD)/nonalcoholic #Steatohepatitis (NASH) (Del Chierico et al., 2017) and for #Juvenile idiopathic arthritis (JIA) [1.32] [#Liver fibrosis] - supplementation with #Lachnospiraceae and #Ruminococcaceae can protect against obesity, inflammation, intestinal dysbiosis, and hepatic #Fibrosis in MASLD [#Liver fibrosis] - reduced abundance of TLR4 ligands in the serum and reduced hepatic TLR expression in mice treated with #Beta-glucan, which suggests a decrease in bacterial translocation due to restored intestinal homeostasis. - TLR4 ligands as an essential driver for intrahepatic fibrosis through the recruitment of Kupffer cells and hepatic stellate cells. - mice treated with #Beta-glucan > significant reduction in MoMFs and Kupffer cells, which are well-established drivers of MASLD progression. [#Liver fibrosis] - increased abundance of the #Ruminococcaceae genus in patients with higher degrees of hepatic fibrosis. - increased abundance of #Ruminococcus following #Beta-glucan treatment > improvement in MASLD progression. [1.33] [#Lactobacillus bulgaricus, #Lactobacillus paracasei, #Lactobacillus plantarum] - Randomized controlled trials in NAFLD patients revealed that administration of polymicrobial probiotics (containing #Bifidobacteria, #Lactobacillus acidophilus, L. bulgaricus, L. paracasei, L. plantarum, and #Streptococcus thermophilus) significantly reduced the fatty liver phenotype, inflammation, and #Fibrosis. - application of #Actinomyces naeslundii and #Veillonella rogosae, which are endemic oral bacteria, had no effect on NAFLD progression. [#Lactococcus lactis] - oral administration of #Nisin, a bacteriocin produced primarily by L. lactis, shifted the oral, gut, and liver microbiome toward a new state commensurate with health > prevented periodontal disease and enteritis, and subsequently reduced the bacterial exposure in the liver > marked protective effect against vacuolar degeneration and fat deposition in the liver [#Porphyromonas gingivalis, #Prevotella intermedia] - mice fed a high-fat diet and inoculated with P. gingivalis or P. intermedia exhibited an altered gut microbiome and blood metabolism, and a shift in hepatic transcriptional expression toward an NAFLD phenotype. [1.34] [#Chronic liver disease] [#Adlercreutzia equolifaciens] [1.35] - the risk for NAFLD significantly decreased as #Flavonoid intake tertiles increased in a stepwise manner [1.36] [#Cirrhosis] - in MAFLD > Microbiome composition was unique in patients with advanced #Fibrosis, who had enriched levels of #Prevotella copri, the most predictive microbiome in the classifier. [#Hepatocellular cancer] - in patients with MAFLD #Cirrhosis, gut microbiota, and systemic inflammation were significantly correlated in the process of hepatocarcinogenesis. [#Human gammaherpesvirus 4] - microbial metabolite, 3-(4-hydroxyphenyl) #Lactate > associate with MAFLD and #Liver fibrosis. - higher plasma #Calprotectin levels are associated with suspected MAFLD and the risk of all-cause mortality. - elevated fecal #Calprotectin (FC) levels in a pediatric cohort, including patients with #Obesity and MAFLD. - #Ruminiclostridium and #Streptococcus were enriched in patients with #Obesity and MAFLD. - these changes remained significant for #Ruminococcaceae UCG-008 even after correction for multiple comparisons - In MAFLD > The dysbiosis-induced release of metabolites, such as #2-butanone and #4-methyl-2-pentanone, along with ethanol production by gut bacteria, contributes to oxidative damage. [#Bile Acids] - patients with lean NAFLD displayed elevated levels of total, primary, and secondary BAs compared to their nonlean counterparts, with statistical significance observed specifically for secondary BAs [#Bile Acids] - Patients with MAFLD show elevated levels of total fecal BAs, including #Cholic acid and #Chenodeoxycholic acid, along with an altered balance of primary and secondary BAs. - in mafld > lean patients exhibited lower levels of #Deoxycholate, #Glycochenodeoxycholic acid, and #Chenodeoxycholic acid but higher levels of #Glycocholic acid compared to nonlean patients. - Patients with lean MAFLD exhibited enrichment in #Erysipelotrichaceae UCG-003, #Ruminococcus, #Clostridium sensu stricto 1, #Romboutsia, and #Ruminococcaceae UCG-008. [#Bile Acids] [#High Fat Diet] - high-fat diets (HFD) have been found to increase specific #Lactobacillus species resistant to BAs, which may influence lipid metabolism and contribute to MAFLD development. [#Metabolic Dysfunction-associated Steatohepatitis] - TLR signaling contributes to the exacerbation of hepatic injury in various chronic liver diseases, encompassing conditions such as alcoholic liver disease (ALD), chronic viral hepatitis, and MAFLD/MASH. [1.37] - patients with MASLD were characterized by a dominance shift toward specific potentially pathogenic bacterial genera (#Serratia and #Aggregatibacter), while the genus Petrobacter was enriched in healthy controls. [1.38] - #3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). [#Akkermansia muciniphila] [#3-succinylated cholic acid] - the beneficial effect of 3-sucCA on MAFLD was reversed by A. muciniphila depletion. [1.39] [#Constitutive androstane receptor , #Diabetes Type 2] [#3,3′-Diindolylmethane] - CAR plays a critical role in regulating the breakdown, uptake and removal of foreign substances in the liver, including drugs. - CAR plays a role in diabetes, fatty liver disease and small intestine #Ulcerative Colitis - The diindoles, diindolylmethane (DIM) and #Diindolylethane (DIE) selectively up-regulate bona fide CAR target genes in primary human hepatocytes and mouse liver without causing significant side effects. References Notes [1.54]
