Liver cancer is usually diagnosed at an advanced stage and is the third most common cause of cancer-related death worldwide. In addition to the lack of effective treatment options, resistance to therapeutic drugs is a major clinical challenge. The gut microbiota has recently been recognized as one of the key factors regulating host health. The microbiota and its metabolites can directly or indirectly regulate gene expression in the liver, leading to gut-liver axis dysregulation, which is closely related to liver cancer occurrence and the treatment response. Gut microbiota disturbance may participate in tumor progression and drug resistance through metabolite production, gene transfer, immune regulation, and other mechanisms. However, systematic reviews on the role of the gut microbiota in drug resistance in liver cancer are lacking. Herein, we review the relationships between the gut microbiota and the occurrence and drug resistance of hepatocellular carcinoma, summarize the emerging mechanisms underlying gut microbiota-mediated drug resistance, and propose new personalized treatment options to overcome this resistance.

Exposure to chemical pollutants and their effects on the gut microbiome during early life are scarce, especially the effects of mixed exposures. Plasma pollutants levels were measured using gas chromatography -triple quadrupole mass spectrometer (GC-MS/MS) among 304 infants in the neonatal ward at Hunan Children's hospital, China, and gut microbiota was derived from 16S rRNA sequencing. We assessed exposure and alpha diversity using generalized linear models, and variation in beta diversity (Bray-Curtis), taxa abundance (MaAsLin2), and employed Bayesian kernel machine regression (BKMR) to investigate the association of pollutants mixture with alpha diversity and taxa. PBDE-99 was positively associated with the Chao1 index (β = 4.29, 95%CI:1.54,7.03). Exposure to the pesticides trifluralin, γ-BHC, and methidathion significantly affected beta diversity (all PFDR < 0.05). PBDE-100, β-BHC, phosalone, methiamitron, fenpropathrin, δ-BHC, and o,p'-DDT were associated with changes in taxa abundance, including negative associations [e.g., Staphylococcus, Bacteroides, Bifidobacterium, and Corynebacterium] and positive associations [e.g., Acinetobacter and Pseudomonas]. An interaction between o,p'-DDT and δ-BHC on Pseudomonas was also found in BKMR models. Our findings suggest that chemical pollutants are associated with gut microbiome changes in hospitalized infants, providing new insights into the mechanisms of chemical pollutants toxicity. Further validation is necessary to confirm these associations and explore their long-term health effects.

Abnormal bile acid (BA) metabolism is involved in liver fibrosis. In a previous study, we discovered that the hydrophobic BA glycochenodeoxycholate (GCDCA) induced liver fibrosis and that GW4064, an agonist of farnesoid X receptor (FXR), alleviated liver fibrosis caused by GCDCA. However, the impacts of GCDCA on liver BAs, gut BAs, the intestinal barrier, and the gut microbiota are unclear, and obtaining this information would provide additional information into the role of GCDCA in the development of liver fibrosis. In the present study, ultra-performance liquid chromatography‒tandem mass spectrometry revealed that mice administered GCDCA by gavage had higher levels of total and primary liver BAs than those in the control group, and a significant reduction in primary liver BAs was observed in the GCDCA + GW4064 group compared with those in the GCDCA group. Compared with those in the control group, the mice administered GCDCA by gavage had greater levels of total and primary BAs in the gut, especially T-alpha-MCA and T-beta-MCA, and no significant differences in the terminal ileum were observed between the GCDCA and GCDCA + GW4064 groups. Immunohistochemistry indicated that GCDCA administration inhibited gut FXR and FGF15 expression, whereas GW4064 activated gut FXR and promoted FGF15 expression. Moreover, immunohistochemistry revealed that GCDCA administration decreased mucin2, claudin-1, occludin, and ZO-1 expression, whereas GW4064 restored their expression. 16S rDNA sequencing revealed that the alpha diversity of the microbiota did not significantly differ among the three groups, but differences in the beta diversity of the microbiota were observed among the three groups. At the phylum level, GCDCA significantly disturbed the gut microbiota, as indicated by reductions in Desulfobacterota, Bacteroidota, and Actinobacteria in the GCDCA group compared with those in the control group. However, significantly increased abundances of Proteobacteria, Cyanobacteria, and Patescibacteria were noted in the GCDCA group compared with the control group. GW4064 administration significantly improved the microbiota structure at the phylum level. The efficacy of GW4064 was also observed at the genus level. Correlation analyses revealed fewer relationships between the gut microbiota and gut BAs, whereas the gut microbiota was more closely related to liver BAs in the GCDCA and GW4064 intervention groups. Together, GCDCA induced cholestasis and disturbed BA metabolism in the gut and liver, as well as the intestinal barrier and structure of the gut microbiota. Activation of gut FXR improved intestinal barrier injury and alleviated BA metabolism dysfunction and dysbacteriosis caused by GCDCA under cholestatic conditions.

Glycochenodeoxycholate (GCDCA) is a hydrophobic bile acid (BA) in humans and is highly increased in the serum and stool of liver fibrosis patients. However, the effects of GCDCA were not comprehensively investigated in the process of liver bile acid metabolism, gut microbiota, and intestinal barrier. It was reported that GCDCA can promote liver fibrosis via the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway in mice, and gut farnesoid X receptor activation alleviated the fibrosis caused by GCDCA in our previous study. Gut microbiota is also responsible for BA metabolism; meanwhile, BA metabolism may also exert an effect on the intestinal barrier. Nowadays, the comprehensive understanding of gut microbiota and intestinal barrier in relation to BA disorder was still insufficient. Current study further investigated the role of GCDCA in BA metabolism, gut microbiota, and intestinal barrier to help understand the effects of GCDCA in liver fibrosis, which may provide intervention methods for liver fibrosis caused by dysregulation of BA metabolism.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease globally. MASLD is a multisystem disease where metabolic dysfunction plays a key role in the development of MASLD and its most relevant liver-related morbidities and extrahepatic complications, such as cardiovascular disease, chronic kidney disease and certain types of extrahepatic cancers. Among the least examined MASLD-related extrahepatic complications, an ever-increasing number of observational studies have reported a positive association between MASLD and the risk of serious bacterial infections (SBI) requiring hospital admission. This risk remained significant in those studies where statistical analysis was adjusted for age, sex, ethnicity, obesity, type 2 diabetes and other common comorbidities. Notably, the incidence rates of SBI were further increased with more advanced MASLD, especially in patients with MASLD-related cirrhosis, and were also observed for some acute viral infections, including SARS-CoV-2 infection, leading to severe COVID-19. In this narrative review article, we provide an overview of the literature on (a) the recent epidemiological data linking MASLD to the risk of serious bacterial and non-bacterial infections requiring hospital admission, (b) the putative underlying mechanisms through which MASLD may increase the susceptibility to serious infections, both directly and through the immune dysfunction associated with cirrhosis and portal hypertension, and (c) the practical and clinical implications of the increased risk of serious bacterial and non-bacterial infections in the growing global population with MASLD.

Cirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity.

Fifteen healthy controls (HCs), as well as 26 patients with stable cirrhosis (SC), 46 with DC, 14 with acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis participated. Metagenomic sequencing was undertaken on paired saliva and faecal samples. 'Salivatypes' and 'enterotypes' based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified.

Salivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs. SC and HCs, independent of antimicrobial, beta-blocker and gastric acid-suppressing therapies. Two distinct gut microbiome clusters harboured genes encoding for the PTS (phosphoenolpyruvate:sugar phosphotransferase system) and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected (575 common to both sites). The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively.

The degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increase significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to patients with severe infection without cirrhosis, supporting the additive pathobiological effect of cirrhosis.

This research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide the development of targeted microbiome-based therapeutics and personalised antimicrobial regimens for patients with cirrhosis to mitigate infectious complications and improve clinical outcomes.

Congenital hepatic fibrosis (CHF) caused by mutations in the polycystic kidney and hepatic disease 1 (PKHD1) gene is a rare genetic disorder with poorly understood pathogenesis. We hypothesized that integrating gut microbiome and metabolomic analyses could uncover distinct host-microbiome interactions in CHF mice compared to wild-type controls.

Pkhd1del3-4/del3-4 mice were generated using CRISPR/Cas9 technology. Fecal samples were collected from 11 Pkhd1del3-4/del3-4 mice and 10 littermate wild-type controls. We conducted a combined study using 16 S rDNA sequencing for microbiome analysis and untargeted metabolomics. The gut microbiome and metabolome data were integrated using Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO), which helped identify key microbial and metabolic features associated with CHF.

CHF mouse model was successfully established. Our analysis revealed that the genera Mucispirillum, Eisenbergiella, and Oscillibacter were core microbiota in CHF, exhibiting significantly higher abundance in Pkhd1del3-4/del3-4 mice and strong positive correlations among them. Network analysis demonstrated robust associations between the gut microbiome and metabolome. Multi-omics dimension reduction analysis demonstrated that both the microbiome and metabolome could effectively distinguish CHF mice from controls, with area under the curve of 0.883 and 0.982, respectively. A significant positive correlation was observed between the gut microbiome and metabolome, highlighting the intricate relationship between these two components.

This study identifies distinct metabolic and microbiome profiles in Pkhd1del3-4/del3-4 mice. Multi-omics analysis effectively differentiates CHF mice from controls and identified potential biomarkers. These findings indicate that gut microbiota and metabolites are integral to the pathogenesis of CHF, offering novel insights into the disease mechanism.

Benzophenone-type ultraviolet filters recently received significant attention to overlook regulatory agencies' safety potential due to their toxicological implications on humans and the environment. The present study has been carried out to explore the toxicity of Benzophenone-3 (BP-3) in earthworm Eisenia fetida. Low-level long-term exposure defiles earthworm health through elevated ROS and its detrimental impact on reproductive organs and reproduction. Based on KEGG and GO analysis, global transcriptomics reveals differentially expressed gene transcripts affecting key signaling pathways. Further validation by q-PCR showed significant upregulated expression of genes involved in stress (CuZn-SOD, CAT), metabolism (GST), reproduction and gametogenesis (ANN and Piwi-2), and endocrine (EcR) functions. Interestingly, lower concentrations of BP-3 are biologically effective in exhibiting a non-linear concentration-response pattern towards the expression of reproduction and endocrine function genes. In addition, BP-3, through soil exposure, significantly alters the gut microbiome by inducing changes in bacterial diversity, while fungal diversity remains unaffected. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes have significantly affected phyla, whereas Ascomycota and Basidiomycota remain dominant, suggesting their potential role in metabolizing or tolerating the BP-3 contamination. The findings highlight the molecular consequences of BP-3 exposure in earthworms and indicate the broader environmental impacts of benzophenone-type organic UV filters on terrestrial biota. The information could also be helpful for chemical risk assessment in soil ecotoxicology.

The gut viral community has been increasingly recognized for its role in human physiology and health; however, our understanding of its genetic makeup, functional potential, and disease associations remains incomplete.

In this study, we collected 11,286 bulk or viral metagenomes from fecal samples across large-scale Chinese populations to establish a Chinese Gut Virus Catalogue (cnGVC) using a de novo virus identification approach. We then examined the diversity and compositional patterns of the gut virome in relation to common diseases by analyzing 6311 bulk metagenomes representing 28 disease or unhealthy states.

The cnGVC contains 93,462 nonredundant viral genomes, with over 70% of these being novel viruses not included in existing gut viral databases. This resource enabled us to characterize the functional diversity and specificity of the gut virome. Using cnGVC, we profiled the gut virome in large-scale populations, assessed sex- and age-related variations, and identified 4238 universal viral signatures of diseases. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.698) and high-risk patients from controls (AUC = 0.761), and its predictive ability was also validated in external cohorts.

Our resources and findings significantly expand the current understanding of the human gut virome and provide a comprehensive view of the associations between gut viruses and common diseases. This will pave the way for novel strategies in the treatment and prevention of these diseases.

Industrialization has driven lifestyle changes in eastern and western Chinese populations, yet we have a poor understanding of the dynamic changes in their gut microbiome and resistome under industrialization, which is essential for the scientific management of public health. Here, this study employed metagenomics to analyze the gut microbiota of 1,382 healthy individuals from China, including 415 individuals from the eastern region of advanced industrialization and 967 individuals from the western region of developing industrialization. Compared with western populations, eastern populations show a significant increase in interindividual dissimilarity of microbial species composition and metabolic pathways but a significant decrease in intraindividual species and functional diversity. Furthermore, our results found significantly less abundance and richness of antibiotic resistance genes (ARGs) in the gut microbiota of eastern populations, alongside a lower prevalence of unique core ARG subtypes. For the 12 core ARG types shared between eastern and western populations, the mean relative abundance of two types was notably higher in the eastern populations, while eight core ARG types had significantly higher mean relative abundance in the western populations. Based on the reconstruction of metagenomic assembled genomes, we found that Escherichia coli genomes from western populations carried more virulence factor genes (VFGs) and mobile genetic elements (MGEs) compared to those from eastern populations. This large-scale study for the first time revealed industrialization potentially led to unexpected alterations of the gut microbiome and resistome between eastern and western populations that provide a vital implication for Chinese public health and may aid in the development of region-specific strategies for managing pathogenic infections.

As China experiences rapid but uneven industrialization, understanding its effect on people's gut bacteria is critical for public health. This study reveals how industrialization may reshape the health risks related to gut bacteria and antibiotic resistance. This work provides crucial information to help create customized public health policies for different regions.

The gut microbiota plays an important role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we aimed to evaluate the role of the butyrate-producing bacterium Faecalibacterium prausnitzii in MASLD and whether supplementation with butyrate-producing bacteria, in particular Faecalibacterium prausnitzii, can ameliorate diet-induced steatohepatitis in mice. The relative abundance of the genus Faecalibacterium and its most abundant strain Faecalibacterium prausnitzii was determined by 16S rRNA sequencing and quantitative polymerase chain reaction (qPCR), respectively, in 95 participants with MASLD and 19 healthy control subjects. Butyrate and butyrate-producing bacteria (Faecalibacterium prausnitzii and Coprococcus comes) were gavaged to C57BL/6 mice fed a steatohepatitis-inducing diet. The fecal relative abundance of Faecalibacterium and Faecalibacterium prausnitzii was decreased in subjects with MASLD versus healthy controls and lower in individuals with MASLD and stage 3-4 fibrosis versus those with stage 0-2 fibrosis. Sodium-butyrate supplementation improved hepatic steatosis in mice on high-fat diet (HFD). Gavage of various butyrate-producing bacteria including Faecalibacterium prausnitzii and Coprococcus comes isolated from humans did not improve HFD-induced liver disease in mice. Although the abundance of Faecalibacterium prausnitzii is associated with MASLD severity in humans, its gavage to mice does not improve experimental diet-induced liver disease.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by organ failure and high short-term mortality. Since its first definition in 2013, many international organizations have defined this syndrome and, till now, there has been no agreement regarding definitions and diagnostic criteria. Although the precise mechanism of ACLF is unknown, precipitant factors and the systemic inflammation response play a major role. Specific management of this high-mortality syndrome is still under development, but a general consensus in the diagnosis and management of ACLF is needed.

Background/Objective: This study investigated the relationship between the composition of oral microbiota and metabolic dysfunction-associated steatotic liver disease (MASLD) in the general population. Methods: In total, 712 participants in a health check-up project were divided into four oral microbiota patterns by principal component analysis and cluster analysis; they were included in Neisseria, Streptococcus, Fusobacterium, and Veillonella groups. The Neisseria group had the largest number of patients and was used as a reference group to compare the incidence of MASLD and cardiometabolic criteria with the other groups. Results: In a multivariate analysis, the Veillonella group was a risk factor for MASLD independent of cardiometabolic criteria compared with the Neisseria group. The correlation between oral bacterial species and MASLD-related items showed that Neisseria was negatively correlated with controlled attenuation parameters, body mass index, waist circumference, hemoglobin A1c, alanine aminotransferase, and fatty liver index. Veillonella showed a positive correlation with controlled attenuation parameters, waist circumference, body mass index, blood pressure, triglycerides, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and fatty liver index, and a negative correlation with high-density lipoprotein cholesterol. In contrast, the Streptococcus and Fusobacterium groups were not clearly associated with MASLD. Conclusions: Maintaining oral hygiene and preventing periodontitis may contribute to preventing MASLD and extending a healthy lifespan.

Transjugular intrahepatic portosystemic shunt (TIPS) placement alleviates portal hypertension symptoms. Hepatic encephalopathy (HE) is a common complication of TIPS, impacting patient quality of life and the healthcare burden. Post-TIPS HE is associated with portosystemic shunting, elevated blood ammonia levels, and inflammation. Increasing attention has been given to the liver and intestinal circulation in recent years. An imbalance in intestinal microecology plays a role in the occurrence of HE and may be a new target for treatment. This review discusses the causes, diagnosis, and treatment strategies for post-TIPS HE and focuses on exploring treatment strategies and their relationships with the gut microbiota, suggesting an innovative approach to address this complication.

The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.

Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing greater oversight guided by a consensus from the research community. One of the most controversial issues in microbiome research is the definition of a 'healthy' human microbiome. This concept is complicated by the microbial variability over different spatial and temporal scales along with the challenge of applying a unified definition to the spectrum of healthy microbiome configurations. In this Perspective, we examine the progress made and the key gaps that remain to be addressed to fully harness the benefits of the human microbiome. We propose a road map to expand our knowledge of the microbiome-health relationship, incorporating epidemiological approaches informed by the unique ecological characteristics of these communities.

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease) is a chronic liver disease affecting over a billion individuals worldwide. MASLD can gradually develop into more severe liver pathologies, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and liver malignancy. Notably, although being a global health problem, there are very limited therapeutic options against MASLD and its related diseases. While a thyroid hormone receptor agonist (resmetirom) is recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in MASLD and MASH incidence, it is urgent to develop novel and effective therapeutic strategies against these prevalent liver diseases. In this article, the pathogenic mechanisms of MASLD and MASH, including insulin resistance, dysregulated nuclear receptor signaling, and genetic risk factors (eg, patatin-like phospholipase domain-containing 3 and hydroxysteroid 17-β dehydrogenase-13), are introduced. Various therapeutic interventions against MASH are then explored, including approved medication (resmetirom), drugs that are currently in clinical trials (eg, glucagon-like peptide 1 receptor agonist, fibroblast growth factor 21 analog, and PPAR agonist), and those failed in previous trials (eg, obeticholic acid and stearoyl-CoA desaturase 1 antagonist). Moreover, given that the role of gut microbes in MASLD is increasingly acknowledged, alterations in the gut microbiota and microbial mechanisms in MASLD development are elucidated. Therapeutic approaches that target the gut microbiota (eg, dietary intervention and probiotics) against MASLD and related diseases are further explored. With better understanding of the multifaceted pathogenic mechanisms, the development of innovative therapeutics that target the root causes of MASLD and MASH is greatly facilitated. The possibility of alleviating MASH and achieving better patient outcomes is within reach. SIGNIFICANCE STATEMENT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, and it can progress to more severe pathologies, including steatohepatitis, cirrhosis, and liver cancer. Better understanding of the pathogenic mechanisms of these diseases has facilitated the development of innovative therapeutic strategies. Moreover, increasing evidence has illustrated the crucial role of gut microbiota in the pathogenesis of MASLD and related diseases. It may be clinically feasible to target gut microbes to alleviate MASLD in the future.

The combination of artificial intelligence (AI) with microbial technology marks the start of a major transformation, improving applications throughout biotechnology, especially in healthcare. With the capability of AI to process vast amounts of biological big data, advanced microbial technology allows for a comprehensive understanding of complex biological systems, advancing disease diagnosis, treatment and the development of microbial therapeutics. This mini review explores the impact of AI-integrated microbial technologies in healthcare, highlighting advancements in microbial biomarker-based diagnosis, the development of microbial therapeutics and the microbial production of therapeutic compounds. This exploration promises significant improvements in the design and implementation of health-related solutions, steering a new era in biotechnological applications.

Background/Objectives:Maerua crassifolia, a threatened medicinal species endemic to drylands, exhibits a pronounced drought sensitivity. Despite the critical role of microorganisms, particularly bacteria and fungi, the microbial consortia in M. crassifolia's rhizosphere remain underexplored. Methods: Metagenomic whole genome shotgun sequencing (WGS) was employed to elucidate the taxonomic composition of bacterial and fungal communities inhabiting the soil rhizosphere of M. crassifolia. Results: The data revealed a marked predominance of bacterial genomes relative to fungal communities, as evidenced by non-redundant gene analysis. Notably, arbuscular mycorrhizal fungi (AMF), specifically Rhizophagus clarus, Rhizophagus irregularis and Funneliformis geosporum, are key rhizosphere colonizers. This study confirmed the presence of phosphate-solubilizing bacteria (PSB), such as Sphingomonas spp., Cyanobacteria and Pseudomonadota, underscoring the critical role of these microorganisms in the phosphorus cycle. Additionally, the study uncovered the presence of previously uncharacterized species within the phylum Actinobacteria, as well as unidentified taxa from the Betaproteobacteria, Gemmatimonadota and Chloroflexota phyla, which may represent novel microbial taxa with potential plant growth-promoting properties. Conclusions: Findings suggest a complex, symbiotic network where AMF facilitate phosphorus uptake through plant-root interactions. In a tripartite symbiosis, PSB enhance inorganic phosphorus solubilization, increasing bioavailability, which AMF assimilate and deliver to plant roots, optimizing nutrition. This bacterial-fungal interplay is essential for plant resilience in arid environments. Future investigations should prioritize the isolation and characterization of underexplored microbial taxa residing in the rhizosphere of M. crassifolia, with particular emphasis on members of the Actinobacteria, Betaproteobacteria, Gemmatimonadota and Chloroflexota phyla to uncover their roles in nutrient acquisition and sustainability.

Bone mass and lean mass decrease with age and these changes are associated with increased fracture risk and sarcopenia. Previous studies demonstrated that a probiotic mixture of Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312 and DSM 15313 (L. Mix) prevents bone loss in ovariectomized (ovx) female mice. The purpose of the present study is to test if the beneficial effect of L. Mix is modified by the diet. Female mice were fed either a high-fat (HFD, 60% kcal from fat) or a low-fat (LFD, 10% kcal from fat) diet and subjected to either sham or ovx surgery and treated with L. Mix for 12 weeks. L. Mix treatment increased total body bone mineral density (p ≤ 0.01), by increasing cortical bone area, and total body lean mass (p = 0.035) in mice on LFD but not in mice on HFD. Metagenome sequencing of cecal content showed that L. Mix treatment increased the relative abundance of Lacticaseibacillus paracasei and, Lactiplantibacillus plantarum, demonstrating successful treatment. In addition, the probiotic treatment affected the overall gut microbiota composition and functionality. These findings demonstrate that the L. Mix in combination with a healthy diet is beneficial for musculoskeletal health in female mice.

Dysbiosis in the bile microbiota of cholangiocarcinoma (CCA) patients suggests a potential role for microbial alterations in the pathogenesis of CCA. This study aimed to investigate bile microbial communities in patients with CCA and compare them to those in individuals with benign biliary diseases as a control (CTR) group. Microbial profiling was conducted using next-generation sequencing (NGS), targeting the V3-V4 regions of the 16S rRNA gene, followed by bioinformatics analysis using the VSEARCH and EzBioCloud platforms. Alpha and beta diversity analyses were performed to assess microbial richness and structural differences. The linear discriminant analysis effect size (LEfSe) was utilized to identify potential microbial biomarkers. Results: This study identified distinct microbial profiles in the two groups at both the phylum and genus levels. In the CTR group, Pseudomonadota (65%) was the dominant phyla, while Bacillota (49%) was more abundant in the CCA group. At the genus level, Escherichia (29%), Enterobacteriaceae (12%), Enterococcus (8%), Ralstonia (8%), and Clostridium (5%) were more prevalent in the CTR group, whereas Streptococcus (34%), Ralstonia (8%), and Veillonella (5%) were dominant in the CCA group. Although an alpha diversity analysis showed no statistically significant differences in species richness or diversity between groups, a beta diversity analysis revealed significant structural differences associated with disease severity. Our comparative microbiome study using LEfSe analysis suggested a statistically significant inhibition of normal intestinal bacterial flora in patients with CCA who had not received any treatment. These findings suggest that microbial dysbiosis may play a role in the pathogenesis of CCA. Specific microbial taxa were identified as potential biomarkers for distinguishing benign from malignant diseases. These results underscore the potential role of microbial dysbiosis in CCA pathogenesis and highlight the bile microbiota's utility as a diagnostic marker for biliary diseases.

Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.

In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.

The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.

ClinicalTrials.gov study identifier NCT04932577.

The role of the gut-liver axis in liver cirrhosis is becoming increasingly recognized. We investigated the fecal microbiome in patients with liver cirrhosis and its potential function as a predictive biomarker of hepatic encephalopathy.

Patients were divided into either a high plasma ammonia (HPA) group or a low plasma ammonia (LPA) group according to the upper limit of normal of plasma ammonia concentration. 16S rRNA sequencing of fecal samples was performed to study how the microbiota affects the clinical symptoms of liver cirrhosis. The Stroop test was used to assess the ability of the brain to inhibit habitual behaviors.

Totally, 21 subjects were enrolled. Among the 18 patients with liver cirrhosis, 14 were male, the age range was 42-56 years, and the plasma ammonia level range was 20-125.9 μmol/l. The Stroop test showed more severe cognitive impairment in HPA than in LPA individuals. At the same time, there were significant differences in fecal microbiome characteristics between the two groups, characterized by a further increase in the abundance of the Proteobacteria phylum in the gut (especially aerobic Enterobacteriaceae). Function predictions of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States in the microbiome further explained the increase in the Enterobacteriaceae-dominated polyamine synthesis pathway in the gut microbiome of HPA groups.

Cirrhotic patients with hyperammonemia have a specific fecal bacterial composition (characterized via expansion of Enterobacteriaceae). The ability to bio-synthesize polyamines that Enterobacteriaceae possesses is likely to be a key factor in the elevation of plasma ammonia.

Periodontitis is an immuno-inflammatory disease of the soft tissues surrounding the teeth. Periodontitis is linked to many communicable and non-communicable diseases such as diabetes, cardiovascular disease, rheumatoid arthritis, and cancers. The oral-systemic link between periodontal disease and systemic diseases is attributed to the spread of inflammation, microbial products and microbes to distant organ systems. Oral bacteria reach the gut via swallowed saliva, whereby they induce gut dysbiosis and gastrointestinal dysfunctions. Some periodontal pathogens like Porphyromonas. gingivalis, Klebsiella, Helicobacter. Pylori, Streptococcus, Veillonella, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus, Haemophilus, Aggregatibacter actinomycetomcommitans and Streptococcus mutans can withstand the unfavorable acidic, survive in the gut and result in gut dysbiosis. Gut dysbiosis increases gut inflammation, and induce dysplastic changes that lead to gut dysfunction. Various studies have linked oral bacteria, and oral-gut axis to various GIT disorders like inflammatory bowel disease, liver diseases, hepatocellular and pancreatic ductal carcinoma, ulcerative colitis, and Crohn's disease. Although the correlation between periodontitis and GIT disorders is well established, the intricate molecular mechanisms by which oral microflora induce these changes have not been discussed extensively. This review comprehensively discusses the intricate and unique molecular and immunological mechanisms by which periodontal pathogens can induce gut dysbiosis and dysfunction.

Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus. Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut-liver-brain axis and identify a promising therapeutic and predictive target for HE.

Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.

Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics.

DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD.

DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.

Acute pancreatitis (AP) represents one of the most common gastrointestinal (GI) diseases; it can manifest in varying degrees of severity, sometimes leading to a life-threatening condition for the patient. Pancreatic ductal adenocarcinoma (PDAC), due to its high malignancy and uncertain prognosis, is widely regarded as one of the most fatal diseases. The increasing prevalence of AP and PDAC represents a major burden on public health and the healthcare system worldwide. The aim of this systematic review was to discuss the current state of knowledge regarding the relationship between the gut microbiota and the incidence, prognosis, diagnosis and treatment of AP and PDAC. To identify studies that analyzed the relationship between the gut microbiota and the occurrence/development of pancreatic diseases or PDAC, the online databases PubMed, Scopus and Google Scholar were searched between November 2023 and January 2024. Finally, 14 publications met the inclusion criteria (1. were conducted exclusively in humans and/or animals; 2. original, published in English in peer-reviewed journals after 2019; 3. described the relationship between gut microbiota and the occurrence of AP or PDAC). The collected studies indicated significant changes in the gut microbiota of patients with AP and PDAC. Moreover, they highlighted the presence of a relationship between the gut microbiota and the occurrence, course, treatment efficiency and prognosis of the disease in question. Further research is needed to understand precisely the relationship between the gut microbiota and the occurrence of pancreatic diseases and whether it may be a starting point for the development of modern forms of therapy based on the use of prebiotics and/or diet to restore the normal composition of the intestinal bacteria.

The gut microbiome is associated with hepatic encephalopathy (HE), but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.

To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.

We searched the PubMed, Web of Science, EMBASE, and Cochrane databases using two keywords, HE, and gut microbiome. According to the inclusion and exclusion criteria, suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE. The data were analyzed using RevMan and STATA.

Seventeen studies were included: (1) A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE [-0.20, 95% confidence interval (CI): -0.28 to -0.13, I2 = 20%]; (2) The relative abundances of Lachnospiraceae (-2.73, 95%CI: -4.58 to -0.87, I2 = 38%) and Ruminococcaceae (-2.93, 95%CI: -4.29 to -1.56, I2 = 0%) in liver cirrhosis patients with HE was significantly lower than those in patients without HE; (3) In patients with HE, Enterococcus, Proteobacteria, Enterococcaceae, and Enterobacteriaceae proportions increased, but Ruminococcaceae, Lachnospiraceae, Prevotellaceae, and Bacteroidetes proportions decreased; (4) Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected; and (5) Differential gut microbiomes may serve as diagnostic and prognostic tools.

The gut microbiomes of patients with liver cirrhosis with and without HE differ. Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.

The hepatoprotective effect of the fruit of Lycium barbarum has been documented in China over millennia. Lycium barbarum polysaccharides (LBPs) were the first macromolecules reported to mitigate liver fibrosis in carbon tetrachloride (CCl4)-treated mice. Herein, a neutral peptidoglycan, named as LBPW, was extracted from the fruit of Lycium barbarum. In this study, we investigated the hepatoprotective mechanisms of LBPW. CCl4-induced liver fibrosis mice were administered LBPW (50, 100, 200 mg ·kg-1 ·d-1, i.p.) or (100, 200, 300 mg· kg-1 ·d-1, i.g.) for 6 weeks. We showed that either i.p. or i.g. administration of LBPW dose-dependently attenuated liver damage and fibrosis in CCl4-treated mice. Pharmacokinetic analysis showed that cyanine 5.5 amine (Cy5.5)-labeled LBPW (Cy5.5-LBPW) could be detected in the liver through i.p. and i.g. administration with i.g.-administered Cy5.5-LBPW mainly accumulating in the intestine. In TGF-β1-stimulated LX-2 cells as well as in the liver of CCl4-treated mice, we demonstrated that LBPW significantly upregulated Smad7, a negative regulator of TGF-β/Smad signaling, to retard the activation of hepatic stellate cells (HSCs) and prevent liver fibrosis. On the other hand, LBPW significantly boosted the abundance of Akkermansia muciniphila (A. muciniphila) and fortified gut barrier function. We demonstrated that A. muciniphila might be responsible for the efficacy of LBPW since decreasing the abundance of this bacterium by antibiotics (Abs) blocked the effectiveness of LBPW. Overall, our results show that LBPW may exert the hepatoprotective effect via rebalancing TGF-β/Smad7 signaling and propagating gut commensal A. muciniphila, suggesting that LBPW could be leading components to be developed as new drug candidates or nutraceuticals against liver fibrosis.

Summaries of the relationships between the microbiota and liver cirrhosis and their conclusions are not consistent. This study describes microbial differences in patients with liver cirrhosis by performing a meta-analysis.

We searched PubMed, Embase, Web of Science, and the Cochrane Library and collected related articles published before March 10, 2024. Ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio (CDR). Using a random-effects model, the standard mean deviation (SMD) and 95% confidence interval (CI) were calculated. We subsequently performed subgroup, sensitivity, and publication bias analyses. cirrhosis dysbiosis ratio.

A total of 53 eligible papers including 5076 participants were included. The pooled estimates revealed a moderately significant reduction in gut microbiome richness in patients with liver cirrhosis compared with controls, including the Shannon, Chao1, observed species, ACE, and PD indices, but no significant difference was observed for the Simpson index. Over 80% of the studies reported significant differences in β diversity. Families Enterobacteriaceae and Pasteurellaceae, belonging to the phylum Proteobacteria, along with the family Streptococcaceae and the genera Haemophilus, Streptococcus, and Veillonella, were significantly associated with liver cirrhosis compared to the control group. In contrast, the healthy group exhibited a higher abundance of the class Clostridia, particularly the families Lachnospiraceae and Ruminococcaceae, which are known for their diversity and role as common gut commensals. Furthermore, the class Bacilli, predominantly represented by the genus Streptococcus, was markedly enriched in the cirrhosis group.

The microbiota richness of liver cirrhosis patients was lower than that of healthy controls. Alterations in gut microbiota linked to liver cirrhosis were characterized by a decrease in Lachnospiraceae, Ruminococcaceae, and Clostridia and an enrichment of Enterobacteriaceae, Pasteurellaceae, Streptococcaceae, Bacilli, and Streptococcus.

Malnutrition affects over 30 million children annually and has profound immediate and enduring repercussions. Survivors often suffer lasting neurocognitive consequences that impact academic performance and socioeconomic outcomes. Mechanistic understanding of the emergence of these consequences is poorly understood. Using multi-system SHAP interpreted random forest models and network analysis, we show that Moderate Acute Malnutrition (MAM) associates with enrichment of faecal Rothia mucilaginosa, Streptococcus salivarius and depletion of Bacteroides fragilis in a cohort of one-year-old children in Dhaka, Bangladesh. These microbiome changes form interconnected pathways that involve reduced plasma odd-chain fatty acid levels, decreased gamma and beta electroencephalogram power in temporal and frontal brain regions, and reduced vocalization. These findings support the hypothesis that prolonged colonization by oral commensal species delay gut microbiome and brain development. While causal links require empirical validation, this study provides insights to improve interventions targeting MAM-associated neurodevelopmental deficits.

Metagenomic studies have revealed the critical roles of complex microbial interactions, including horizontal gene transfer (HGT) and functional redundancy (FR), in shaping the gut microbiome's functional capacity and resilience. However, the lack of comprehensive data integration and systematic analysis approaches has limited the in-depth exploration of HGT and FR dynamics across large-scale gut microbiome datasets. To address this gap, we present GutMetaNet (https://gutmetanet.deepomics.org/), a first-of-its-kind database integrating extensive human gut microbiome data with comprehensive HGT and FR analyses. GutMetaNet contains 21 567 human gut metagenome samples with whole-genome shotgun sequencing data related to various health conditions. Through systematic analysis, we have characterized the taxonomic profiles and FR profiles, and identified 14 636 HGT events using a shared reference genome database across the collected samples. These HGT events have been curated into 8049 clusters, which are annotated with categorized mobile genetic elements, including transposons, prophages, integrative mobilizable elements, genomic islands, integrative conjugative elements and group II introns. Additionally, GutMetaNet incorporates automated analyses and visualizations for the HGT events and FR, serving as an efficient platform for in-depth exploration of the interactions among gut microbiome taxa and their implications for human health.

Pathogenic microorganisms pose a severe risk to the aquatic environment and human health. Membrane bioreactors (MBRs) have attracted much attention due to their simultaneous biological treatment and virus retention, but membrane fouling is the main obstacle. This study explored the effect of micro-granular activated carbon (μGAC) on bacteriophage MS2 removal efficiency and membrane fouling in a flat-plate MBR. The results showed that the μGAC addition with a particle size of 180-300 μm improved the removal of MS2 (LRVMBR of 4.77 log) and enhanced the removal of COD and ammonia nitrogen. The μGAC integrated MBR (μGAC-MBR) exhibited a higher MS2 retention rate by the membrane filter layers with an average LVRMem of 2.03 log compared to that of a control reactor (C-MBR) of 1.89 log. Meanwhile, the total membrane filter layer resistance of μGAC-MBR was significantly lower than that of C-MBR, particularly in terms of cake layer resistance and organic pore-blocking exclusion. The μGAC addition slightly reduced MS2 adsorption by the activated sludge while significantly altering the extracellular polymeric substances (EPS) profiles. The fluorescent components in the bound EPS and PN/PS ratio of the activated sludge were reduced. We found that μGAC enhanced membrane surface roughness and hydrophilicity. Notably, the μGAC significantly influenced the quorum sensing (QS) systems, reducing the abundance and synthesis of AHL-related genes. The synthase luxI in the AHL-QS system was reduced by 93.21% in μGAC-MBR. The AHL-QS system is closely related to biofilm formation, and the total EPS of the surface filer layer of μGAC-MBR decreased by 57.73%, and PN in LB-EPS and TB-EPS decreased by 91.33% and 54.44% compared with C-MBR, indicating a significant reduction in biofilm formation. This study exhibited a new perspective on promoting MS2 removal with the synergistic effect of alleviating fouling in the MBR process.

Microbiome profiling tools rely on reference catalogues, which significantly affect their performance. Comparing them is, however, challenging, mainly due to differences in their native catalogues. In this study, we present a novel standardized benchmarking framework that makes such comparisons more accurate. We decided not to customize databases but to translate results to a common reference to use the tools with their native environment. Specifically, we conducted two realistic simulations of gut microbiome samples, each based on a specific taxonomic profiler, and used two different taxonomic references to project their results, namely the Genome Taxonomy Database and the Unified Human Gastrointestinal Genome. To demonstrate the importance of using such a framework, we evaluated four established profilers as well as the impact of the simulations and that of the common taxonomic references on the perceived performance of these profilers. Finally, we provide guidelines to enhance future profiler comparisons for human microbiome ecosystems: (i) use or create realistic simulations tailored to your biological context (BC), (ii) identify a common feature space suited to your BC and independent of the catalogues used by the profilers and (iii) apply a comprehensive set of metrics covering accuracy (sensitivity/precision), overall representativity (richness/Shannon) and quantification (UniFrac and/or Aitchison distance).