Liver regeneration is increasingly recognized as a process influenced not only by hepatocellular signaling but also by the gut-liver axis, where gut microbiota-derived metabolites, immune mediators, and extracellular vesicles modulate hepatic recovery after liver damage. In this review, we explore recent progress in understanding the gut microbiota's role in liver regeneration and discuss its therapeutic potential in the context of hepatic surgery and liver transplantation. Emerging evidence shows that beneficial microbial taxa, including Akkermansia muciniphila, Bifidobacterium longum, and Parabacteroides distasonis, enhance liver regeneration by regulating short-chain fatty acid production, bile acid metabolism, and tricarboxylic acid cycle pathways, while dysbiosis and microbial translocation can impair regenerative outcomes. Key host-microbiome interactions, particularly the Farnesoid X Receptor (FXR)-Fibroblast Growth Factor 19 (FGF19) signaling axis, play a central role in protecting hepatocytes from bile acid overload and supporting regeneration, highlighting the therapeutic potential of FXR agonists, FGF19 mimetics, probiotics, dietary interventions, and metabolite supplementation. At the same time, monitoring bile acids profiles alongside gut microbiota composition may allow early detection and prevention of complications. In addition, microbial-derived markers such as the lipopolysaccharide/lipoteichoic acid ratio may serve as predictive biomarkers for post-hepatectomy liver failure. Adjunctive approaches, including vitamin D supplementation, may further support regeneration through vitamin D receptor-mediated regulation of bile acid homeostasis and cell-cycle progression. In the context of live donor liver transplantation, the detection of occult bacteremia further underscores the complexity of host-microbiome interactions and suggests that microbiological surveillance could improve postoperative management. Collectively, these findings emphasize the importance of microbiota-targeted strategies to improve hepatic regeneration, reduce postoperative complications, and optimize outcomes following liver surgery and transplantation.
Radiation nephropathy is a progressive inflammatory and fibrotic condition lacking effective therapies. The underlying cellular signalling mechanisms and their potential systemic involvement remain poorly defined. We integrated single-cell transcriptomics, network pharmacology, molecular docking and dynamics simulations, and in vivo validation in a murine model of whole-body irradiation. RNA sequencing data from healthy and irradiated mouse kidneys were analyzed to map cell-type-specific signalling activities of mTORC1, endoplasmic reticulum (ER) stress, and inflammation, as well as intercellular communication. Mice received diosgenin at 30 or 100 mg/kg/d by orally or rapamycin at 2 mg/kg/d by intraperitoneal injection for 7 days before and 28 days after 5 Gy X-ray irradiation. Renal function, histopathology, oxidative stress, inflammatory cytokines, intestinal barrier integrity, hepatic inflammation, and gut microbiota were assessed. Bulk transcriptomics and network pharmacology identified mTOR as a core target. Single-cell analysis revealed radiation-induced mTORC1 activation in proximal tubular cells and immune cells, coupled with ER stress and inflammation. Molecular docking predicted high binding affinity between diosgenin and mTOR. Molecular dynamics simulations confirmed stable diosgenin-mTOR binding over 100 ns. In vivo, diosgenin suppressed renal mTORC1 activity, reduced ER stress, and macrophage infiltration, lowered serum TNF-α, IL-1β, and IL-6, and decreased serum urea and creatinine by approximately 30.25% and 26.20%, respectively. Diosgenin alleviated renal fibrosis, restored colonic occludin expression by 1.5-fold, decreased hepatic F4/80-positive cells by 75.32%, reversed gut dysbiosis including suppression of Pseudomonadota, and these effects were similar to those of rapamycin, an mTOR inhibitor. Diosgenin alleviates radiation nephropathy by suppressing mTORC1 signalling while exerting concomitant effects on the gut and liver. These findings establish a multi-omics and single-cell framework for radiation nephropathy and support diosgenin as a candidate for translational research.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease, affecting over 30% of adults worldwide. Emerging evidence suggests that dietary fibre, particularly pectin, may improve metabolic health by modulating inflammation, gut microbiota composition, and intestinal permeability. However, controlled human studies in MASLD are limited. This study aims to evaluate the effect of pectin supplementation on systemic inflammation, gut microbiome, and metabolic health in patients with MASLD. This single-centre, double-blind, randomised, placebo-controlled dietary intervention will be conducted at Nottingham University Hospitals NHS Trust in partnership with the University of Nottingham. Thirty adults with MASLD will be randomised (1:1) to receive either 15g/day Low-methoxyl (LM) pectin or a matched placebo for six weeks. Each participant will attend baseline and post-intervention visits during which anthropometric data, fasting blood samples, and stool samples will be collected. FibroScan® assessments will be performed for all participants at both visits to quantify liver stiffness and steatosis. Twenty-two participants will take part in a magnetic resonance imaging (MRI) sub-study to evaluate hepatic and intestinal characteristics at baseline and post-intervention. Laboratory analyses will include liver function, lipid, glycemic, and inflammatory markers, alongside profiling of gut microbiota composition and short-chain fatty acids. This is the first randomised controlled study to evaluate the mechanistic effects of pectin supplementation on inflammation, gut microbiome composition, and metabolic outcomes in MASLD. The results may generate novel evidence on the role of soluble fibre in modulating the gut-liver axis and support the development of scalable, nutrition-based interventions to improve metabolic and hepatic health in this population. The trial was registered on ClinicalTrials.gov (Identifier: NCT07093346).
Postoperative infection remains a major cause of morbidity after liver transplantation (LT) in patients with liver failure. Increasing evidence suggests that gut microbiota dysbiosis may contribute to infection risk, but its dynamic changes after LT are not fully understood. This retrospective study included 60 patients with liver failure who underwent LT and developed postoperative infection-related risk. Patients were divided into a probiotic group and a non-probiotic group. Fecal samples were collected before transplantation and on postoperative days 7, 14, 21, and 28. Metagenomic sequencing was performed to analyze gut microbial composition, diversity, and antibiotic resistance genes. The probiotic group showed a significantly lower rate of postoperative bacterial infection, especially intra-abdominal infection. After LT, gut microbiota gradually recovered in both groups, but restoration was faster in the probiotic group. The non-probiotic group showed persistent dysbiosis, characterized by enrichment of opportunistic pathogens such as Enterococcus and Klebsiella, whereas beneficial genera including Bifidobacterium and Lactobacillus were more abundant in the probiotic group. Antibiotic resistance genes were also more enriched in the non-probiotic group. Early postoperative gut microbiota reconstruction is closely associated with infectious complications after LT, and modulation of gut microbiota may help improve postoperative outcomes.
As one of the most consumed meat products globally, microplastics (MPs) residues in chickens may enter the human body through the food chain. Therefore, this study aimed to investigate the adverse effects of MPs exposure on chicken health and the detoxification mechanisms of astaxanthin (AST). We found that MPs significantly impaired liver function, inducing injury characterized by hepatocyte ferroptosis, inflammation, lipid disorder, and fibrosis. This hepatic damage was linked to MPs-induced gut microbiota dysbiosis and disruption of the intestinal barrier. AST exerted hepatoprotective effects by activating the Nrf2/HO-1 signaling pathway and attenuating hepatic oxidative stress and ferroptosis. In parallel, AST improved gut microbiota composition and intestinal barrier integrity, thereby potentially reducing gut-derived inflammatory burden. Together, these findings suggest that AST confers liver protection through both direct hepatic actions and indirect modulation of the gut-liver axis.
Hawthorn procyanidin extract (HPC) is one of natural plant-derived polyphenols with lipid-lowering and liver-protective properties, while its therapeutic mechanisms against nonalcoholic fatty liver disease (NAFLD) require further clarification. A high-fat diet (HFD)-induced NAFLD mouse model and oleic acid (OA)-induced HepG2 cells were utilized to conduct this study. We first found that HPC intervention ameliorated lipid accumulation in HepG2 cells, which was confirmed to depend on FXR signaling using an FXR inhibitior. In addition, HPC significantly relieved NAFLD in vivo by lowering the levels of TC, TG, and LDL-C and preventing the excessive accumulation of lipid droplets and hepatic steatosis. Besides, HPC intervention restored BA homeostasis (in the liver and gut) by markedly altering the profiles of primary versus secondary and conjugated versus unconjugated BAs (ωMCA, TαMCA, TβMCA, and DCA), which was related to the restoration of the HFD-induced dysbiosis. Mechanistically, HPC downregulated the expression of lipid synthesis protein SREBP1 by activating the hepatic FXR and CYP7A1 expressions, attributed to the controlling of the enterohepatic circulation mediated by the FXR-FGF15 pathway. Taken together, these findings substantiate that HPC exerts its ameliorative effect on NAFLD by modulating BA metabolism in NAFLD mice.
Ketone bodies, particularly β-hydroxybutyrate (3HB), are often elevated in type 1 diabetes (T1D); however, their physiological roles remain unclear. In a low-carbohydrate diet study, patients with insulin-deficient diabetes exhibited reduced fasting blood glucose and increased fasting blood ketone levels, negatively correlated. Another clinical study using continuous glucose and ketone monitoring confirmed inverse glucose-ketone fluctuations. To test causality, we conducted animal and cellular studies. In streptozotocin-induced T1D mice, 7-week oral 3HB administration improved glucose metabolism and alleviated glycogenic hepatopathy. Imaging with 2-deoxy-2-[18F]-fluoro-d-glucose positron emission tomography/computed tomography demonstrated reduced hepatic and intestinal glucose uptake. Western blotting confirmed 3HB suppressed glucose transporter (sodium-glucose cotransporter 1, GLUT2, GLUT5) overexpression and normalized glycogen metabolism. In vitro, 3HB dose-dependently inhibited glucose transporter expression and glucose uptake in primary hepatocytes and IEC-6 cells. G protein-coupled receptor 109A (GPR109A) serves as the primary receptor for 3HB. Mechanistic studies using the GPR109A inhibitor mepenzolate bromide, the mTOR inhibitor rapamycin, and siRNA-mediated gene silencing revealed that these effects were GPR109A dependent and linked to inhibition of the PI3K/AKT/mTOR pathway. Overall, this study provides new insights into the role of ketone bodies in T1D, establishing 3HB as a modulator of glucose homeostasis through GPR109A-mediated suppression of glucose transporters in the liver and intestine.
Early-life nutritional overfeeding is increasingly recognized as a critical driver of metabolic programming and long-term obesity risk. This study investigated the protective effects and underlying mechanisms of Bifidobacterium animalis DPU-MWFBA, designated as FBA-40, against early-life overfeeding-induced obesity and metabolic dysfunction. An early overfeeding mouse model was established by small-litter rearing, followed by a two-week oral intervention with FBA-40. FBA-40 significantly attenuated excessive body weight gain and adiposity, improved glucose tolerance and insulin sensitivity, and alleviated dyslipidemia, systemic inflammation, and hepatic dysfunction. Histological analyses showed that FBA-40 reduced hepatic lipid accumulation and improved liver morphology. In addition, colonic histology and immunohistochemistry demonstrated that FBA-40 preserved intestinal barrier integrity by increasing ZO-1 and Occludin expression while suppressing TNF-α-associated inflammatory activation. Gut microbiota analysis revealed that FBA-40 restored microbial richness and diversity and reshaped gut microbial composition toward a more metabolically favorable profile. Hepatic transcriptomic analysis further showed that FBA-40 reprogrammed lipid metabolism-, oxidative stress-, and inflammation-related pathways, particularly PPAR signaling, linoleic acid metabolism, cholesterol metabolism, bile secretion, and arachidonic acid metabolism. qRT-PCR and estern blot validation confirmed that FBA-40 suppressed lipogenesis-related targets, including Scd1, Acaca, Lpin1, and SCD1, while restoring PPARα/EHHADH-associated fatty acid β-oxidation and GPX1-mediated antioxidant defense. Collectively, these findings demonstrate that FBA-40 alleviates early-life overfeeding-induced metabolic dysfunction by coordinating gut microbial remodeling, intestinal barrier protection, and hepatic lipid metabolic reprogramming. This study provides mechanistic evidence supporting FBA-40 as a promising early-life probiotic candidate for preventing obesity and associated metabolic disorders.
In recent years, heat stroke (HS) have been reported with increasing frequency, and this trend is hard to separate from broader environmental changes, including climate change, recurrent extreme heat events, and air pollution. When people are exposed to high-temperature environments for a prolonged period, especially during intense physical activity, the condition may progress to HS. HS is an acute and potentially fatal disorder that can deteriorate rapidly if not treated in time. The intestine appears to be particularly vulnerable during HS. HS can disrupt intestinal tight junctions and weaken the barrier function of the gut, leading to what is commonly described as a "leaky gut." Once this barrier is compromised, microbial products such as lipopolysaccharides can enter the bloodstream. These molecules may then activate immune cells, promote excessive cytokine release, and eventually drive a systemic inflammatory response. In severe cases, this inflammatory process can develop into systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Current evidence increasingly suggests that intestinal injury is not simply a secondary result of HS. Rather, it may serve as an important early event in the development and progression of the disease. Still, it should be noted that much of the available evidence comes from preclinical studies, and strong clinical confirmation is still limited. Probiotics have attracted attention because they may help reduce the occurrence and severity of HS by maintaining gut microbiota balance and regulating intestinal immune responses. However, since most supporting data are still derived from animal experiments, their protective effects in humans need to be interpreted carefully. Another point worth emphasizing is that the gut is not working alone. Through gut-organ communication networks, the intestinal microbiota can interact with distant organs, including the liver, lungs, and brain. These gut-liver, gut-lung, and gut-brain axes may help explain how HS leads to injury beyond the intestine itself. In this review, we summarize current findings on how modulation of the gut microbiota may improve intestinal thermotolerance and strengthen barrier function, with the aim of providing useful insights for the prevention and treatment of HS in clinical practice.
Developmental data from necrophagous flies are widely used to estimate the minimum postmortem interval (PMImin), but their reliability may be affected by larval feeding substrate and associated gut microbiota. Under controlled laboratory conditions, we investigated the effects of three porcine tissues (liver, lung, and muscle) on the development and gut microbial communities of Sarcophaga peregrina (Robineau-Desvoidy) (Diptera: Sarcophagidae). Developmental duration, larval body length, and pupal length were recorded, and gut samples from six developmental stages were analyzed by 16S rRNA gene sequencing. Feeding substrate affected development mainly during the feeding stages, with the second instar showing the greatest sensitivity. Larvae reared on liver developed significantly faster than those reared on muscle, whereas maximum larval length did not differ among groups; pupae from the liver group were significantly larger. Gut microbiota analysis showed that developmental stage was the primary driver of community succession, while feeding substrate further shaped microbial divergence during feeding. The dominant bacterial phyla across samples were Pseudomonadota, Bacillota, and Bacteroidota. The liver-fed group was enriched in Bacillota-associated taxa, including Vagococcus, Lactococcus, and Peptostreptococcus, whereas the lung- and muscle-fed groups showed greater enrichment of Wohlfahrtiimonas, Ignatzschineria, and Providencia. LEfSe, functional prediction, and random forest classification further supported clear substrate-associated differences. These findings show that tissue substrate influences both development and gut microbial succession in S. peregrina and may affect PMImin interpretation.
Bile acids (BAs), once often considered tumor-promoting, are now recognized for their complex roles in breast cancer. Their effects are influenced by the gut microbiota and may vary across cancer subtypes and exposure contexts. This systematic review aims to summarize the current evidence on the clinical relevance, molecular mechanisms, and therapeutic applications of BAs in breast cancer. We performed a systematic literature search of four international (PubMed, Web of Science, Embase, Cochrane Library) and two Chinese (China National Knowledge Infrastructure, Wanfang) databases, along with clinical trial registries, from inception to February 8, 2026. Study selection adhered to PRISMA guidelines, and we focused on original studies investigating the role of BAs in breast cancer pathogenesis, therapy, or drug development. Evidence mapping across clinical profiling, receptor biology, direct BA interventions, and translational applications indicates that human BA measurements do not converge on a stable systemic "BA signature". Our qualitative heterogeneity assessment indicates that the apparent contradictions are largely driven by differences in exposure compartment, comparator definition, analytical platform and BA speciation/coverage, and variable control of clinical confounders and subtype/stage or treatment background. When these sources of heterogeneity are considered, more coherent patterns emerge: receptor studies support context-dependent outputs across tumor subtypes and microenvironmental states, while direct BA interventions report both anti-tumor and pro-tumor phenotypes that depend strongly on BA species/form and concentration, with many in vitro experiments using pharmacologic or supraphysiologic exposures. In translational research, BAs have been explored as active derivatives targeting defined pathways and as enabling components in drug delivery systems. In the latter setting, BAs mainly serve as biocompatible scaffolds to improve delivery of established chemotherapeutics in preclinical models. The BA system represents a promising but challenging therapeutic target for breast cancer. However, its clinical translation requires carefully designed strategies to overcome major hurdles. The inherent lack of tissue specificity poses risks for systemic toxicity. Future efforts must focus on developing tumor-targeted approaches, understanding the gut-microbiome-liver-breast axis, and performing subtype-stratified (especially estrogen receptor status-stratified) research to establish robust patient stratification biomarkers and safely realize the potential of BA-based therapies.
Gastric acid-suppressive medications, particularly proton pump inhibitors (PPIs), are commonly used in patients with alcohol-associated liver disease (ALD) to prevent and manage upper gastrointestinal bleeding, gastroesophageal reflux disease, and non-steroidal anti-inflammatory/aspirin-induced gastroesophageal damage. By inhibiting the gastric H⁺/K⁺-ATPase, PPIs suppress acid secretion and impair bacterial killing, thereby promoting gut dysbiosis that disrupts barrier integrity and enhances bacterial translocation, ultimately exacerbating liver injury. PPIs are frequently co-administered with antibiotics for indications such as gastrointestinal bleeding, Spontaneous Bacterial Peritonitis (SBP), other infections, or hepatic encephalopathy prophylaxis, but the consequences of this combined therapy on gut microbial ecology and disease outcomes remain unclear. Our study addresses this gap by showing how PPI use, alone or with antibiotics, reshapes the gut microbiome and aggravates liver disease progression. In previous studies, we showed that PPIs promote dysbiosis and ALD progression in mice and humans by facilitating intestinal expansion and hepatic translocation of Gram-positive Enterococcus. Fecal cytolysin, an Enterococcus faecalis exotoxin that induces hepatocyte death, predicts mortality in patients with alcohol-associated hepatitis (AH). In this study, we have examined the mechanism by which PPIs alone and in combination with non-absorbable antibiotics targeting Gram-positive bacteria influence ALD, as well as the disease mechanisms associated with cytolytic Enterococcus faecalis and the development of therapeutic strategies. In mice, alcohol administration during gastric acid suppression promoted expansion of Gram-positive taxa, including cytolysin-producing Enterococcus. Similarly, PPI use in patients with AH was associated with increased fecal Enterococcus and higher 30-d mortality, underscoring the translational relevance of our findings. Unexpectedly, treatment of acid-suppressed mice with non-absorbable antibiotics designed to suppress Gram-positive bacteria worsened ethanol-induced steatohepatitis: while Enterococcus abundance decreased, Streptococcus and other potentially pathogenic taxa expanded, leading to increased bacterial translocation and aggravated liver injury. In patients with cirrhosis or metabolic dysfunction-associated steatotic liver disease (MASLD), PPIs did not promote Enterococcus expansion, indicating etiology-dependent microbiome responses. Finally, we identified dipalmitoylphosphatidylcholine and Caspase-1 inhibitor as in vitro and in vivo modulators of cytolysin activity, highlighting potential therapeutic avenues. Collectively, our study demonstrates how PPIs and non-absorbable antibiotics targeting Gram-positive bacteria interact with the gut microbiome to drive ALD, underscoring the need for careful therapeutic management.
This study assessed the burden of liver cancer (LC) and its major risk factors from 1990 to 2021, with projections to 2050. The global and regional LC burden from 1990 to 2021 was extracted from the Global Burden of Disease Study 2021, and stratified by age, sex, Sociodemographic Index (SDI), region, and etiological category. Trends for the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life year rate (ASDR) were evaluated using estimated annual percentage changes. Attributable risk factors, including alcohol use, drug use, a high body mass index, tobacco use, and high fasting plasma glucose levels, were examined. Projections of the LC burden to 2050 were modeled under baseline and hypothetical risk elimination scenarios. The global ASMR of LC remained stable, from 5.86 per 100,000 population (95% uncertainty interval [UI], 5.38 to 6.46) in 1990 to 5.65 (95% UI, 5.13 to 6.30) in 2021. Regions with an initially high ASMR showed increases until the early 2000s, then decreased. The LC burden increased sharply with age and was consistently higher in males, particularly in high-SDI regions. Mortality varied by etiology, with hepatitis B virus as the leading cause, followed by hepatitis C virus and alcohol use. Major risk factors were alcohol and tobacco use among males and drug and alcohol use among females. By 2050, the ASMR and ASDR of LC are projected to reach 6.23 per 100,000 population (95% UI, 4.94 to 8.09) and 158.91 (95% UI, 125.34 to 210.28), respectively, but could decrease to 5.32 (95% UI, 4.21 to 6.95) and 135.33 (95% UI, 106.74 to 179.05) under improved metabolic and behavioral risk scenarios. Despite public health interventions, LC is estimated to maintain a significant global burden.
Natto, a well-known fermented soybean product beneficial for bone health, remains unclear in its mechanism. This study investigated its effect on secondary osteoporosis (OP) in mice. Natto significantly inhibited weight loss, bone quality deterioration, and bone morphological damage, and regulated OPG/RANKL pathway protein expression (p < 0.05) in OP mice. Analysis of 16S rRNA revealed that natto increased gut microbiota α-diversity and the abundance of Sutterella, Roseburia, and Coprococcus, while reducing harmful bacteria such as Streptococcus, Shigella, and Helicobacter. These microbial changes positively correlated with body weight, bone size, and serum osteogenic metabolism in OP mice. Serum metabolomics showed differential metabolites of the natto group enriched in PPAR signaling and primary bile acid biosynthesis. Verification by mRNA and ELISA indicated that the upregulated liver and circulating PPARα by natto may regulate downstream bile acid pathways, linking gut microbiota to multi-organ metabolic functions. In summary, natto may act on gut microbiota to alleviate bone loss via the "gut microbiota-bile acid-OPG/RANKL" network, targeting multiple organs including gut, liver, and bone. This provides a theoretical basis for natto dietary intervention in osteoporosis prevention through the gut-bone axis.
Obesity negatively impacts maternal and fetal metabolism, leading to the programming of metabolic disturbances in the offspring. We have previously reported numerous maternal, fetal and offspring alterations in a rat model of obesity. In this study, we administered butyrate-a short-chain fatty acid derived from gut microbiota metabolism-to obese mother rats during pregnancy and lactation in an attempt to improve maternal health and prevent the fetal features associated with the programming of fatty liver disease. The initial experimental study design comprised female Albino-Wistar rats assigned to either a control diet (C group) or a high-fat diet (FD group) to induce obesity, before being paired with control males. Pregnant rats received either butyrate (CB or FDB) or water as a vehicle (C or FD) during gestation and were euthanized at day 21 of pregnancy. The second experimental design comprised C, FD, and FDB rats that gave birth and breastfed their pups, with mothers being euthanized at the conclusion of the lactation period. At term gestation, rats with obesity exhibited increased adiposity, hepatic lipid accumulation, triglyceridemia, and circulating IL-1β. Their fetuses displayed increased body weight, liver lipid over-accumulation, and altered mRNA levels of genes involved in liver damage. Notably, butyrate administration decreased maternal circulating levels of triglycerides and IL-1β, and prevented fetal overweight status and hepatic lipid accumulation at term gestation. Importantly, butyrate exerted no effect on control rats or their fetuses. Moreover, butyrate administration ameliorated features of fatty liver disease in overweight rats at the end of lactation, further demonstrating its beneficial effects on both mothers and fetuses in this rat model of obesity.
Campilobacteriosis is the most frequently reported zoonosis in the European Union. Poultry and poultry products are the primary sources of human infection. The high occurrence of antibiotic-resistant (AR) Campylobacter strains is particularly concerning, as it complicates treatment and poses a serious public health threat. Therefore, this study assessed the prevalence of AR C. coli recovered from the gut and liver of broiler chickens from northeastern Spain. Using the broth microdilution method and whole genome sequencing (WGS) with Illumina HiSeq, the AR of 40 C. coli strains (n = 18 from liver; n = 22 from gut) was assessed. Phenotypically, all isolates were resistant to ciprofloxacin (100%), followed by tetracycline (95%), while co-resistance to both constituted the most prevalent profile (25%). Moderate to high resistance frequencies were observed to erythromycin (53%), ertapenem (28%) and gentamicin (23%). Overall, 70% of the isolates showed a multidrug resistant (MDR) phenotype. The origin of the strain (caeca or liver) did not influence the occurrence of AR. WGS revealed that all isolates harbored the gyrA T86I mutation conferring ciprofloxacin resistance while most tetracycline-resistant isolates (80%) carried the tet(O) gene. Macrolide-resistant isolates either exhibited a point mutation in the 23S rDNA or the 50S ribosomal L22 protein gene, or harbored ermB and erm(53) genes. BlaOXA genes were present in 72.5% of the ertapenem-resistant strains; however, ertapenem-specific resistance was not identified and might involve the CmeABC efflux pump with certain blaOXA genes. Among gentamicin resistant strains, 78% harbored the aph(2″) gene conferring resistance to this antibiotic. All isolates carried genes coding for the CmeABC and CmeDEF efflux pumps conferring unspecific AR. Overall, a strong concordance between phenotypes and genotypes was seen, with WGS analysis also revealing additional putative resistance determinants and predicting 92.5% MDR strains. This study highlights the potential risk of chickens and chicken livers as a source of AR C. coli and emphasizes WGS as a valuable tool providing significant additional information on the AR potential of C. coli isolates.
Background/Objectives As a fat-soluble vitamin, vitamin E (VE) is prone to suboptimal intake in the general population. Alpha-tocopherol (α-TE) represents the most biologically significant form of VE in vivo. Nevertheless, the potential detrimental effects of α-TE deficiency on health remain unclear. This study was conducted to investigate the effect of α-TE deficiency on hepatic metabolism and gut microbiota. Methods C57BL/6J mice were randomly assigned to receive one of three dietary regimens: a α-TE-deficient diet, a control diet with normal α-TE, or a high-dose diet containing four times the normal α-TE level. Histopathology, serum biochemistry, RNA-Seq, RT-qPCR, Western blot, and 16S rRNA gene sequencing with correlation analysis were used to assess metabolic phenotypes, hepatic circadian, hepatic lipid metabolism, and cecal microbiota, respectively. Results The results demonstrated that α-TE deficiency induced hepatic steatosis and lipid metabolic disturbances. α-TE deficiency significantly decreased Arntl and Clock expression, but increased Per2. Additionally, it upregulated the expression of lipogenic genes such as Scd1, Elovl6, and Elovl3 and simultaneously downregulated fatty acid oxidation genes such as Cyp4a10, Cyp4a14, and Acot1, bringing about imbalance in lipid homeostasis. In addition, α-TE deficiency greatly changed the structure and composition of gut microbiota. Bacterial genera like Alistipes, norank_f__Muribaculaceae, Muribaculum, Odoribacter, and Dubosiella were significantly correlated with hepatic circadian and lipid metabolism gene expression with the strongest correlation being Alistipes. Conclusions This work is the first to reveal that short term α-TE deficiency could cause lipid metabolic disorder via the "gut microbiota-liver circadian clock" axis, which provides novel insights into the etiology of nutrition-related metabolic diseases and targets for nutritional intervention.
1. Lead (Pb) and cadmium (Cd) induce liver damage mainly via oxidative stress. Total saponins from ginseng stems and leaves (TSGSL) possess antioxidant properties, but their protective effect against Pb-Cd co-exposure remains unclear.2. This study aimed to investigate the hepatoprotective effect and mechanism of TSGSL in acute Pb-Cd co-exposed mice.3. Male KM mice received TSGSL (30 or 60 mg/kg, orally) once daily for 14 days, then a single acute exposure to Pb (150 mg/kg) and Cd (15 mg/kg). Liver function, oxidative stress markers, histopathology, pro-inflammatory cytokines, and Keap1/Nrf2 pathway gene mRNA were assessed.4. TSGSL dose-dependently alleviated Pb-Cd-induced liver injury. At 60 mg/kg, it reduced ALT by 46.0% and AST by 43.3%, decreased hepatic MDA by 50.0%, increased hepatic T-SOD, CAT and GSH-PX by 36.9%, 69.5% and 36.7%, respectively, and lowered pro-inflammatory cytokines (e.g. TNF-α by 51.7% and IL-1β by 46.0%). Histopathological damage was ameliorated. TSGSL upregulated mRNA expression of Keap1/Nrf2-related genes. The 30 mg/kg dose showed weaker effects.5. TSGSL protects against acute Pb-Cd-induced oxidative liver damage in mice, potentially via transcriptional upregulation of the Keap1/Nrf2 pathway and enhancement of antioxidant capacity. Further studies are needed to investigate chronic Pb-Cd co-exposure and gut microbiota involvement.
Hepatic encephalopathy (HE) remains a major cause of hospitalization and readmission in cirrhosis and is closely linked to hyperammonemia, microbial dysbiosis, impaired short-chain fatty acid (SCFA) output, barrier dysfunction, and altered mucosal immunity. We evaluated whether adding a multistrain probiotic to rifaximin was associated with greater neurometabolic improvement and coordinated gut-liver-brain axis changes. In this prospective, 6-month, randomized, open-label, assessor-blinded, three-arm controlled study, 61 adults with cirrhosis-related HE received standard care alone (Con, n = 20), standard care plus rifaximin 550 mg twice daily (Rif, n = 20), or rifaximin plus a multistrain probiotic (1 × 10^9 CFU three times daily; Rif + Pro, n = 21). The main prespecified biochemical readout was serum ammonia at Month 6. A composite HE index incorporating mental status, flapping tremor, number connection test, and ammonia grade was analyzed as a prespecified exploratory neurometabolic score. A predefined mechanistic subset underwent 16S rRNA microbiome profiling, serum SCFA measurement, and fecal secretory IgA (SIgA) testing. Baseline characteristics did not differ across arms. Post-treatment serum ammonia decreased in a graded pattern (Con 177 ± 43.2, Rif 143 ± 37.5, Rif + Pro 117 ± 34.3 μmol/L), with parallel improvement in the exploratory HE index (10.0 ± 4.9, 5.3 ± 4.7, and 3.7 ± 4.1, respectively). In the mechanistic subset, the microbial community structure differed by treatment (PERMANOVA p = 0.006). Rif + Pro was associated with higher serum propionate, increased Lactobacillus salivarius-associated signal, reduced Bacteroides ovatus-associated signal, and marked fecal SIgA elevation compared with standard care or rifaximin alone. The SIgA-propionate relationship was interpreted as exploratory. Rifaximin plus multistrain probiotics was associated with greater improvement in serum ammonia and exploratory HE severity readouts than rifaximin alone, accompanied by coordinated microbial, metabolic, and mucosal immune changes. These findings support confirmation in adequately powered event-driven trials with strain-resolved profiling and targeted metabolomics.
Micro- and nanoplastics (MNPs) are emerging environmental contaminants of increasing relevance to human health. Growing evidence suggests that, following ingestion, inhalation, or, less convincingly, dermal exposure, MNPs may cross biological barriers, enter lymphatic and vascular compartments, and reach the liver. Owing to portal blood flow, sinusoidal architecture and Kupffer cell activity, the liver appears to be one of the principal sites of early particle sequestration. Human biomonitoring, ex vivo and postmortem studies have detected MNPs in blood and multiple organs, including the liver, although the currently available evidence remains limited and methodologically heterogeneous. Their identification relies on multistep analytical procedures that integrate sample pretreatment with FTIR, Raman spectroscopy, LD-IR, Py-GC-MS and supplementary imaging methods. However, each of these techniques presents significant limitations, particularly in the analysis of nanoplastics. Experimental studies indicate that MNPs may induce hepatic injury through oxidative stress, mitochondrial impairment, endoplasmic reticulum stress, inflammation, DNA damage, dysregulated lipid metabolism and disruption of the gut-liver axis, consequently contributing to steatosis, cholestatic anomalies and fibrosis. Consequently, MNPs should be considered potential contributors to liver pathology, although more comprehensive human data are still required.