Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes the transfer of methyl groups to phosphatidylethanolamine to generate phosphatidylcholine (PC). PC produced de novo through this pathway is preferentially used for very-low-density lipoprotein assembly and is essential for its normal hepatic secretion as well as for bile acid detoxification. While human PEMT loss-of-function polymorphisms are linked to increased metabolic dysfunction-associated steatotic liver disease risk, the enzyme's role as a primary driver of progressive liver disease remains underexplored. We utilized PEMT knockout (PEMT KO) mice on a standard chow diet to model this deficiency. Histopathological analysis showed that while 2-month-old PEMT KO mice were protected, 6-month-old KOs of both sexes spontaneously developed extensive micro- and macrovesicular steatosis, parenchymal inflammation, and granulomatous inclusions. This severe, age-dependent pathology was confirmed by elevated hepatic triglyceride levels, bile acids, impaired methylation potential, and a cascade of secondary injuries, including increased oxidative stress, impaired proteasomal function, and the induction of cellular senescence markers. This bile acid toxicity and oxidative stress activated the central innate immune sensor, the NLRP3 inflammasome, driving pronounced macrophage infiltration and chronic inflammation. Picrosirius red staining and protein analysis confirmed the progression to severe pericellular fibrosis. Our study establishes that PEMT deficiency is sufficient to initiate and drive the complete progression from steatosis to advanced liver fibrosis, identifying PEMT as a critical metabolic checkpoint and a potent therapeutic target for mitigating progressive liver disease.

Platycodin D ameliorates antibiotic-associated diarrhea by modulating the PI3K/AKT/NF-κB pathway and regulating gut microbiota and metabolism.

Diagnosis and management of immune effector cell-associated enterocolitis after ciltacabtagene autoleucel.

Isoastragaloside II modulates PPAR-α/FXR signaling and bile acid metabolism to ameliorate cholestatic liver diseases (CLD).

1,2,4-trimethoxybenzene exerts multi-target effects against ulcerative colitis by inhibiting the NLRP3 inflammasome and remodeling the gut microbiota-metabolism axis.

Mechanisms and key active ingredients of HeDan capsules in ameliorating MASLD via bile acid metabolism regulation.

Cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are characterized by disrupted bile acid (BA) homeostasis and subsequent liver injury. Emerging evidence indicates that circadian rhythms significantly influence liver metabolism and the pathogenesis of liver diseases. CD36 has been identified as a regulator of the hepatic circadian clock and metabolic processes; however, the specific mechanisms by which CD36 links circadian rhythms to cholestatic liver disease remain unclear. In this study, we employed bile duct ligation (BDL) mice and liver-specific CD36 knockout (CD36 LKO) mice to examine the role of CD36 in BA metabolism and circadian gene expression. BDL mice presented disrupted rhythms in both liver clock and BA metabolism, accompanied by increased diurnal expression of CD36. Conversely, in the context of BDL, CD36 LKO reduced cholestatic liver injury, improved BA metabolism, and restored diurnal variation of BA levels. Transcriptomic analysis revealed that BA metabolism genes were regulated by CD36, particularly those involved in synthesis, which displayed diurnal variation. Targeted inhibition of CD36 expression effectively mitigated liver injury and inflammation in BDL mice by restoring the rhythmicity of HMGCR/CYP7A1 and normalizing the BA pool size. These findings suggest that CD36 plays a pro-cholestatic role through its regulation of rhythmic BA synthesis and that its inhibition may represent a promising therapeutic strategy for cholestatic liver diseases.

Smokers with multiple sclerosis (MS) experience worse disease, yet underlying mechanisms remain unknown. Smoking disrupts bile acid and tryptophan metabolism in non-MS populations; both pathways involve host-microbiome co-metabolism and have been linked to MS. Determine whether smoking perturbs these metabolic pathways in MS and whether such alterations statistically mediate smoking's effect on MS severity. We analyzed serum bile acid, tryptophan, and tobacco-related metabolites across four independent MS cohorts (N = 266) using discovery-replication analyses. Mixed-effects regression assessed replicating associations with current smoking and nicotine exposure. Mediation analyses tested if replicating metabolites were potential mediators between smoking and MS severity. Hypothesis-generating metagenomic analyses explored smoking-associated gut-microbial shifts and metabolite correlations. Current smokers and nicotine-exposed MS subjects had reductions in bile acids and tryptophan metabolites, notably indolepropionate, a neuroprotective, anti-inflammatory gut-microbial metabolite. Lower indolepropionate statistically mediated ~20% of smoking's adverse effect on MS severity. Metagenomic analyses identified potential smoking-enriched MS-linked taxa, and that indolepropionate broadly co-occurs with microbial networks (e.g. Lachnoclostridium appeared inversely associated with indolepropionate in smokers with MS). Tobacco exposure disrupts host-microbiome tryptophan and bile acid metabolism in persons with multiple sclerosis, with indolepropionate depletion partially mediating disease severity, highlighting a potential mechanistic pathway warranting further investigation in MS smokers.

Bile salt-mediated activation of a type-1 nuclear receptor of Fasciola gigantica (FgNR1).

Mechanism and interventions of the bile acid-gut-liver axis imbalance in the progression of non-alcoholic fatty liver disease.

Evaluation of probiotic properties of lactic acid bacteria (LAB) strain GXMU-G1 against Vibrio parahaemolyticus and isolation and purification of its bacteriocin.

Vpa1463, a DUF1566-domain protein, is indispensable for bile resistance and biofilm formation in Vibrio parahaemolyticus and is required for its adaptation to food-related environments.

Zhujing Pill ameliorates age-related macular degeneration by regulating lipid metabolism, complement activation, and inflammatory responses: an integrated network pharmacology and metabolomics study.

Disturbances in the infant gut microbiome (GM) may increase the risk of developing allergies. This critical developmental period is characterized by rapid microbial colonization, which is influenced by factors like delivery mode and infant feeding practices. The present study investigated changes in key GM taxa and fecal metabolites in relation to allergy development, delivery mode, age, and infant feeding practices during the first year of life. Seventy-two infants at risk of allergies, exclusively breastfed for at least 16 weeks, were followed in their first year. During this period, allergy manifestations were recorded and fecal samples collected at three time points. The samples were subjected to metabolic profiling covering host and microbial metabolites and fluorescent in situ hybridization to quantify Bifidobacterium spp. and the Eubacterium rectale/Clostridium coccoides group. Strong age-associated metabolic shifts were observed, particularly in aromatic amino acid metabolites, bile acids, B vitamins, and short and long-chain fatty acids. Feeding practices, specifically the introduction of complementary feeding and the cessation of breastfeeding were significantly associated with changes to the fecal metabolome. Delivery mode had a pronounced impact on the metabolome, with differences between vaginal and Cesarean deliveries persisting until 6 months of age. Infants who developed an allergy during this period had lower Bifidobacterium spp. and significantly higher polyunsaturated fatty acid levels before the age of 16 weeks. This study offers valuable insights into the longitudinal development of the fecal metabolome and factors influencing it during infancy, a critical period for immune system development. Clinicaltrials.gov identifier: NCT03067714, registered: 01/02/2017.

Interfering with the response of bacterial pathogens to host substances: An unexplored strategy to control bacterial diseases in aquaculture.

Cerebrotendinous xanthomatosis (CTX) is rare, autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in CYP27A1, which encodes sterile 27 hydroxylase, a key enzyme in bile acid biosynthesis. Enzyme deficiency results in reduced cholic and chenodeoxycholic acid synthesis with accumulation of cholestanol, bile acid intermediates, and bile alcohols, producing a progressive multisystem disorder characterized by chronic diarrhea, juvenile-onset cataracts, tendons xanthomas, and neurological dysfunction. Although CTX typically begins in childhood, diagnosis is frequently delayed until adulthood, limiting the benefit of effective disease modifying therapy with chenodeoxycholic acid. Since the identification of CYP27A1, more than 200 pathogenic variants have been reported, including canonical loss of function alleles and missense variants with variable residual enzyme activity. In this review, we summarize the medical genetics, population genetics and genotype phenotype relationships of CTX. We highlight insights from large population databases that refine global incidence estimates, revealing population-specific enrichment of pathogenic variants and persistent underdiagnosis. We further review functional and clinical data demonstrating that stratification of CYP27A1 variants by functional effect,complete loss of function versus hypomorph alleles,correlates with clinical severity and biochemical phenotype. Finally, we discuss emerging advances in biochemical testing and newborn screening strategies that offer the potential for presymptomatic diagnosis, enabling timely initiation of therapy and prevention of irreversible disease manifestations. Integrating molecular, functional, and population genetic data provides a framework for improved variant interpretation, earlier diagnosis, and optimized therapeutic intervention in CTX.

Bile acids as the silent harbinger: Early signals of portal hypertension after "successful" Kasai.

A multidimensional strategy for identifying quality markers of Radix ginseng-Schisandra chinensis in the disruption of the inflammation-cancer transformation process of hepatocellular carcinoma based on metabolic regulation and chemical properties.

Pharmaceutical optimization of chitosan tablets is associated with reduced circulating bile acids and fibrosis-related molecular signatures in non-alcoholic steatohepatitis rats.

Microbiota metabolite lithocholic acid in cancer: Mechanisms and therapeutic potential.