The gut microbiota is an indispensable symbiotic entity within the human holobiont, serving as a critical regulator of host lipid metabolism homeostasis. Therefore, it has emerged as a central subject of research in the pathophysiology of metabolic disorders. This microbial consortium orchestrates key aspects of host lipid dynamics-including absorption, metabolism, and storage-through multifaceted mechanisms such as the enzymatic processing of dietary polysaccharides, the facilitation of long-chain fatty acid uptake by intestinal epithelial cells (IECs), and the bidirectional modulation of adipose tissue functionality. Mounting evidence underscores that gut microbiota-derived metabolites not only directly mediate canonical lipid metabolic pathways but also interface with host immune pathways, epigenetic machinery, and circadian regulatory systems, thereby establishing an intricate crosstalk that coordinates systemic metabolic outputs. Perturbations in microbial composition (dysbiosis) drive pathological disruptions to lipid homeostasis, serving as a pathogenic driver for conditions such as obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD). This review systematically examines the emerging mechanistic insights into the gut microbiota-mediated regulation of intestinal lipid metabolism, while it elucidates its translational implications for understanding metabolic disease pathogenesis and developing targeted therapies.
Humans ; Gastrointestinal Microbiome/physiology* ; Lipid Metabolism ; Animals ; Intestinal Mucosa/metabolism* ; Homeostasis ; Dysbiosis ; Obesity/metabolism* ; Intestines/microbiology* ; Non-alcoholic Fatty Liver Disease/metabolism* ; Metabolic Diseases/metabolism*

Alcoholic liver disease is a leading cause of morbidity and liver-related death worldwide. Intestinal bacterial overgrowth and dysbiosis induced by ethanol ingestion play an important role in the pathogenesis of alcoholic liver disease. After exposure to alcohol in the lumen, enteric bacteria alter their metabolism and thereby disturb intestinal homeostasis. Disruption of the mucosal barrier results in the translocation of microbial products that contribute to liver disease by inducing hepatic inflammation. In this review, we will discuss the effects of alcohol on the intestinal microbiome, and in particular, its effects on bacterial metabolism, bacterial translocation and ecological balance. A better understanding of the interactions among alcohol, the host and the microbiome will reveal new targets for therapy and lead to new treatments.
Bacterial Translocation/physiology ; Central Nervous System Depressants/metabolism ; Ethanol/metabolism ; Humans ; Intestines/*microbiology ; Lipopolysaccharides/physiology ; Liver Diseases, Alcoholic/*microbiology ; Microbiota/*physiology ; Permeability

OBJECTIVETo study the structural shifts of gut flora in rats with acute alcoholic liver injury (AALI), and the effect of jianpi huoxue decoction (JPHXD) on the gut flora.

METHODSThirty-six Sprague-Dawley rats were randomly allocated to the control, AALI and JPHXD groups equally. The rats in the control group were given water and those in AALI and JPHXD groups were given ethanol by intragastric gavage for 5 days, while rats in the JPHXD group were administered JPHXD simultaneously. The blood and liver tissue were collected at the end of the experiment. The activities of serum alkaline aminotransferase (ALT), aspartate aminotransferase (AST), hepatic γ-glutamyltranspetidase (γ-GT) and hepatic triglyceride (TG) levels were determined. Plasma endotoxin level in the portal vein was measured. Pathological changes of liver tissues were determined by hematoxylin and eosin (HE) staining and oil red O staining. The total DNA of gut flora were extracted from fecal samples by Bead-beating method and determined by ERIC-PCR fingerprint method. The similarity cluster analysis and principal component analysis were performed to analyze the ERIC-PCR fingerprint respectively.

RESULTSIn the AALI group, the ratio of liver/body weight, activities of ALT, AST and hepatic γ-GT, amount of hepatic TG were elevated significantly compared with those in the control group (all P<0.01). JPHXD decreased the ratio, activities of ALT, AST, γ-GT and TG significantly compared with those in the AALI group (P<0.05 or P<0.01). HE and oil red O staining showed that fat deposited markedly in liver tissue, while JPHXD alleviated pathological changes markedly. Plasma LPS level in rat portal vein in the AALI group increased significantly (P<0.01), but it was decreased significantly in the JPHXD group (P<0.01). The cluster analysis and principal component analysis of ERIC-PCR fingerprint showed that gut flora in the AALI group changed markedly, and JPHXD could recover gut flora to some extent.

CONCLUSIONSThe structure of gut flora shifted markedly during acute alcoholic liver injury, JPHXD had prevention effect through the modification of gut flora.

Animals ; Azo Compounds ; metabolism ; Bacteria ; genetics ; Body Weight ; Cluster Analysis ; Consensus Sequence ; genetics ; DNA Fingerprinting ; methods ; DNA, Intergenic ; genetics ; Drugs, Chinese Herbal ; therapeutic use ; Freezing ; Gastrointestinal Tract ; microbiology ; pathology ; Liver ; microbiology ; pathology ; Liver Diseases, Alcoholic ; drug therapy ; microbiology ; pathology ; Organ Size ; Phylogeny ; Polymerase Chain Reaction ; methods ; Principal Component Analysis ; Rats ; Rats, Sprague-Dawley ; Repetitive Sequences, Nucleic Acid ; genetics ; Staining and Labeling

OBJECTIVETo investigate the influence of genetic polymorphism in NF-E2-related factor-2 (nrf2) gene promoter locus at 336 in alcoholic liver disease (ALD) with Vibrio vulnificus (VV) sepsis.

METHODSThrough the simple random sampling method, C57B6 male mice were divided into normal feeding group (group A, 10 mice), alcoholic liver disease group (group B, 10 mice), normal feeding group infected with VV through intraperitoneal injection (group C, 8 mice), alcoholic liver disease group infected with VV (group D, 110 mice). Through gene sequencing method, nrf2 gene promoter 336 polymorphism in D group was analyzed and grouped into: non-mutation group (336T) (group D1, 7 mice) and mutation group (336C) (group D2, 10 mice). Through RT-PCR, Western-blotting and ELISA method, expressions of nrf2, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), high mobility group protein 1 (HMGB(1)) gene and protein of liver were measured. The pathological changes in liver were recorded with light microscope.

RESULTSAfter infected with VV for 48 hours for A, B, C, D1, D2 group, the expression medians of nrf2 mRNA in liver were 0.115, 0.173, 0.211, 0.764, 0.352, respectively (χ(2) = 40.64, P < 0.05), the expression medians of IL-10 mRNA in liver were 0.338, 0.637, 1.002, 1.825, 1.403, respectively (χ(2) = 41.05, P < 0.05), the expression medians of TNF-α mRNA in liver were 0.140, 0.254, 0.372, 0.399, 0.699, respectively (χ(2) = 38.16, P < 0.05), the expression medians of HMGB(1) mRNA in liver were 0.230, 0.410, 0.668, 0.508, 1.021, respectively (χ(2) = 31.45, P < 0.05). After infected with VV 48 hours for mice in A, B, C, D1, D2 group, the expression medians of nrf2 protein in liver were 0.908, 1.461, 2.061, 3.982, 2.243, respectively (χ(2) = 33.72, P < 0.05), the expression medians of IL-10 protein in liver were 13.97, 22.54, 30.14, 57.98, 41.53, respectively (χ(2) = 37.31, P < 0.05), the expression medians of TNF-α protein in liver were 114.07, 142.94, 175.44, 174.60, 266.11, respectively (χ(2) = 32.29, P < 0.05), the expression medians of HMGB(1) protein in liver were 2.01, 6.05, 9.62, 6.24, 12.89, respectively (χ(2) = 36.94, P < 0.05). Compared with group A, there were large amount of fat drops, fatty changes in group B, inflammatory cell infiltration, disorder of hepatic cell in group C, and extension of hepatic duct and vein, edema of liver cells and disorder of hepatic cells in group D.

CONCLUSIONThe nrf2 gene promoter of T336C mutation in C57B6 mouse of ALD can significantly decrease the expression of nrf2, and intensify organ inflammation and damage when they were infected by VV.

Animals ; Liver Diseases, Alcoholic ; complications ; genetics ; metabolism ; microbiology ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2 ; genetics ; metabolism ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Sepsis ; complications ; genetics ; microbiology ; Vibrio Infections ; complications ; genetics ; Vibrio vulnificus

BACKGROUNDSepticemia and inflammation-mediated septic shock caused by Vibrio vulnificus (VV) is strongly associated with chronic liver disease. This study examined the effects of antimicrobial therapy on expression of hepatic toll-like receptors and inflammatory cytokines in rats with alcohol-induced liver disease complicated by VV sepsis.

METHODSMale Sprague-Dawley rats were assigned to the following treatment groups: normal control (N), alcoholic liver disease control (A), antimicrobial-treated alcoholic liver disease control (AA), alcoholic liver disease with VV sepsis (AV), and antimicrobial-treated alcoholic liver disease with VV sepsis (AVA). Alcohol-induced liver disease was observed in all groups except N. Expression of mRNAs encoding hepatic toll-like receptors 2 and 4, myeloid differentiation protein-2, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and IL-10 was determined by RT-PCR.

RESULTSmRNAs encoding toll-like receptors 2 and 4 and myeloid differentiation protein-2 were significantly up-regulated in group AV as compared to control groups at 2 - 24 hours of sepsis; peak expression occurred at 12 hours. These mRNAs were also up-regulated in group AVA but to lesser degrees than in group AV at comparable time post-infection. mRNAs encoding TNF-alpha, IL-1beta and IL-6 were significantly elevated in group AV as a function of infection. In group AVA as compared to AV, expression of TNF-alpha and IL-1beta mRNAs was lower at 12 - 24 hours post-infection and expression of IL-6 mRNA was lower at 24 hours post-infection. Compared with control groups, IL-10 mRNA expression in group AV was markedly higher at 12 - 24 hours of sepsis. Expression of IL-10 mRNA was lower in group AVA as compared to AV at 24 hours of sepsis.

CONCLUSIONSAntimicrobial therapy reduces expression of toll-like receptors and cytokines in rats with alcohol-induced liver disease complicated by VV sepsis. Monitoring hepatic toll-like receptor and cytokine expression during antibiotic therapy may be valuable for determining the course of VV sepsis in subjects with liver disease.

Adaptor Proteins, Signal Transducing ; genetics ; Animals ; Anti-Infective Agents ; therapeutic use ; Cytokines ; genetics ; Interleukin-10 ; genetics ; Interleukin-1beta ; genetics ; Interleukin-6 ; genetics ; Liver ; drug effects ; metabolism ; Liver Diseases, Alcoholic ; drug therapy ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sepsis ; drug therapy ; genetics ; microbiology ; Toll-Like Receptor 2 ; genetics ; Toll-Like Receptor 4 ; genetics ; Toll-Like Receptors ; genetics ; Tumor Necrosis Factor-alpha ; genetics ; Vibrio Infections ; drug therapy ; Vibrio vulnificus ; physiology

OBJECTIVETo study the effects and mechanisms of Jianpi Liqi Huoxue Decoction (JLHD) in anti-alcoholic liver injury (ALI) through the pathological relation of ALI with changes of intestinal permeability and endotoxin leakage.

METHODSThe liver injury model induced by Lieber-DeCarli alcoholic forage was established. Altogether 42 male SD rats were randomly divided into 4 groups, the normal group (n=6), the control group fed with non-alcohol diet (n=12), the model group fed with alcoholic diet (n=12) and the treated group fed with alcoholic diet and treated with JLHD (n=12). The medicine or distilled water was administered by gavage from the 3rd week to the end of the 6th week. Then after fasting for 5 h all the rats except those in the normal group were given lipopolysaccharide (LPS) 10 mg/kg by gavage, and the blood plasma from portal vein, serum from inferior cava vein as well as tissues of liver and intestine were prepared for detection of plasma LPS level in the portal vein to observe the change of intestinal permeability through LPS content in portal vein blood plasma, the pathological and ultrastructural changes of the small intestine by HE staining, the pathological change of liver and triglyceride (TG) content and gamma glutamyl transpeptidase (GGT) activity in liver, the changes of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, and plasma tumor necrosis factor-alpha (TNF-alpha) level.

RESULTSIn rats after modeling, there were obvious fatty degeneration, significant increase of hepatic TG content and GGT activity, serum ALT and AST activity, as well as plasma TNF-alpha level, with high plasma LPS level indicating increased intestinal permeability, and seriously injured mucosa microvilla of small intestine. However, all the above abnormal changes were milder in the treated group than those in the model group. Meanwhile, the TNF-alpha content, endotoxin level and ALT activity were found to be positively correlated.

CONCLUSIONJLHD could alleviate liver injury through inhibiting the alcohol induced increased intestinal permeability and lessening endotoxin leakage.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Endotoxins ; metabolism ; Intestinal Mucosa ; metabolism ; Intestine, Small ; microbiology ; pathology ; Liver Diseases, Alcoholic ; drug therapy ; microbiology ; pathology ; Male ; Permeability ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley