High methionine intake alters gut microbiota and lipid profile and leads to liver steatosis in mice.

Methionine is an important sulfur-containing amino acid. Health effects of both methionine restriction (MR) and methionine supplementation (MS) have been studied. This study aimed to investigate the impact of a high-methionine diet (HMD) (1.64% methionine) on both the gut and liver functions in mice through multi-omic analyses. Hepatic steatosis and compromised gut barrier function were observed in mice fed the HMD. RNA-sequencing (RNA-seq) analysis of liver gene expression patterns revealed the upregulation of lipid synthesis and degradation pathways, cholesterol metabolism and inflammation-related nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Metagenomic sequencing of cecal content demonstrated a shift in gut microbial composition with an increased abundance of opportunistic pathogens and gut microbial functions with up-regulated lipopolysaccharide (LPS) biosynthesis in mice fed HMD. Metabolomic study of cecal content showed an altered gut lipid profile and the level of bioactive lipids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), palmitoylethanolamide (PEA), linoleoyl ethanolamide (LEA) and arachidonoyl ethanolamide (AEA), that carry anti-inflammatory effects significantly reduced in the gut of mice fed the HMD. Correlation analysis demonstrated that gut microbiota was highly associated with liver and gut functions and gut bioactive lipid content. In conclusion, this study suggested that the HMD exerted negative impacts on both the gut and liver, and an adequate amount of methionine intake should be carefully determined to ensure normal physiological function without causing adverse effects.

Differences in the Ability of Lactic Acid Bacteria To Prevent Acute Alcohol-Induced Liver Injury via the Gut Microbiota-Bile Acid-Liver Axis.

Probiotics can regulate gut microbiota and protect against acute alcohol-induced liver injury through the gut-liver axis. However, efficacy is strain-dependent, and their mechanism remains unclear. This study investigated the effect of lactic acid bacteria (LAB), including Lacticaseibacillus paracasei E10 (E10), Lactiplantibacillus plantarum M (M), Lacticaseibacillus rhamnosus LGG (LGG), Lacticaseibacillus paracasei JN-1 (JN-1), and Lacticaseibacillus paracasei JN-8 (JN-8), on the prevention of acute alcoholic liver injury in mice. We found that LAB pretreatment reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) and reduced hepatic total cholesterol (TC) and triglyceride (TG). JN-8 pretreatment exhibited superior efficacy in improving hepatic antioxidation. LGG and JN-8 pretreatment significantly attenuated hepatic and colonic inflammation by decreasing the expression of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) and increasing the expression of interleukin 10 (IL-10). JN-1 and JN-8 pretreatments have better preventive effects than other LAB pretreatment on intestinal barrier dysfunction. In addition, the LAB pretreatment improved gut microbial dysbiosis and bile acid (BA) metabolic abnormality. All of the strains were confirmed to have bile salt deconjugation capacities in vitro, where M and JN-8 displayed higher activities. This study provides new insights into the prevention and mechanism of LAB strains in preventing acute alcoholic liver injury.

Restricted intake of sulfur-containing amino acids reversed the hepatic injury induced by excess Desulfovibrio through gut-liver axis.

Diet is a key player in gut-liver axis. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used rodent standard chow and purified diet to mimic two common human dietary patterns: grain and plant-based diet and refined-food-based diet, respectively and explored their impacts on gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in Desulfovibrio, gut bile acid (BA) levels elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation and elevated gut BA levels also occurred in mice fed with the chow diet after receiving Desulfovibrio desulfuricans ATCC 29,577 (DSV). Restriction of sulfur-containing amino acids (SAAs) prevented liver injury mainly through higher hepatic antioxidant and detoxifying ability and reversed the elevated BA levels due to excess Desulfovibrio. Ex vivo fermentation of human fecal microbiota with primary BAs demonstrated that DSV enhanced production of secondary BAs. Higher concentration of both primary and secondary BAs were found in the gut of germ-free mice after receiving DSV. In conclusion, Restriction of SAAs in diet may become an effective dietary intervention to prevent liver injury associated with excess Desulfovibrio in the gut.

Causal associations between platelet count, alcohol consumption, and the risk of liver hepatocellular carcinoma based on a Mendelian randomization study.

Background and aims: Liver hepatocellular carcinoma (LIHC) exhibits a multifactorial etiology, insidious onset, and a significantly low 5-year survival rate. We aimed to evaluate the causal impact of exposure factors (Alzheimer's disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis) on the risk of LIHC using a two-sample Mendelian randomization (MR) study. Methods: Independent single nucleotide polymorphisms (SNPs) strongly associated with Alzheimer's disease, platelet count, ambidextrousness, daily cigarette consumption, alcohol intake, and endocarditis were selected as instrumental variables (IVs) from the corresponding genome-wide association studies (GWAS). Genetic summary statistics for LIHC came from a GWAS that included 168 cases and 372,016 controls of European individuals. Multivariable MR analyses were performed to find the causal association between 6 exposure factors and LIHC risk. The inverse-variance weighted (IVW)-MR was employed as the primary analysis, and the MR-Egger regression, LASSO regression, and weighted Median approaches were performed as complementary analyses. Results: Multivariable MR analysis showed causal association between Alzheimer's disease [Odds ratio (OR) = 0.9999, 95% confidence intervals (CI) = 0.9998-0.9999, p = 0.0010], platelet count (OR = 0.9997, 95% CI = 0.9995-0.9999, p = 0.0066), alcohol consumption (OR = 0.9994, 95% CI = 0.9990-0.9999, p = 0.0098) and the LIHC outcome. After IVW-MR, MR-Egger and LASSO tests, the results are still significant. Next, we used different MR Methods to analyze platelet count, alcohol consumption, and Alzheimer's disease separately. Moreover, both funnel plots and MR-Egger intercepts provided compelling evidence to refute the presence of directional pleiotropy in the association between platelet count, alcohol consumption, Alzheimer's disease and the risk of LIHC. The IVW-MR analysis revealed a significant causal association between an elevated platelet count and a reduced risk of LIHC (OR = 0.9996, 95% CI= 0.9995-0.9998, p = 0.0005). Similarly, the analysis of weighted median revealed a negative correlation between platelet count and the risk of LIHC (OR = 0.9995, 95% CI = 0.9993-0.9999; p = 0.0160). Conversely, we observed a positive causal effect of alcohol consumption on the incidence of LIHC (OR = 1.0004, 95% CI = 0.9999-1.0009). However, no significant causal relationship was found between alcohol assumption, Alzheimer's disease, and LIHC susceptibility. Conclusions: A significant causal relationship exists between platelet count, alcohol consumption, Alzheimer's disease, and an increased risk of LIHC. The study presents compelling evidence for a genetically predicted decreased susceptibility to LIHC based on platelet count. The research implies that elevated platelet count may serve as a protective mechanism against LIHC. These findings may inform clinical strategies for LIHC prevention.

Unveiling the mechanism of efficient ß-phenylethyl alcohol conversion in wild-type Saccharomyces cerevisiae WY319 through multi-omics analysis.

ß-Phenylethanol (2-PE), as an important flavor component in wine, is widely used in the fields of flavor chemistry and food health. 2-PE can be sustainably produced through Saccharomyces cerevisiae. Although significant progress has been made in obtaining high-yield strains, as well as improving the synthesis pathways of 2-PE, there still lies a gap between these two fields to unpin. In this study, the macroscopic metabolic characteristics of high-yield and low-yield 2-PE strains were systematically compared and analyzed. The results indicated that the production potential of the high-yield strain might be contributed to the enhancement of respiratory metabolism and the high tolerance to 2-PE. Furthermore, this hypothesis was confirmed through comparative genomics. Meanwhile, transcriptome analysis at key specific growth rates revealed that the collective upregulation of mitochondrial functional gene clusters plays a more prominent role in the production process of 2-PE. Finally, findings from untargeted metabolomics suggested that by enhancing respiratory metabolism and reducing the Crabtree effect, the accumulation of metabolites resisting high 2-PE stress was observed, such as intracellular amino acids and purines. Hence, this strategy provided a richer supply of precursors and cofactors, effectively promoting the synthesis of 2-PE. In short, this study provides a bridge for studying the metabolic mechanism of high-yield 2-PE strains with the subsequent targeted strengthening of relevant synthetic pathways. It also provides insights for the synthesis of nonalcoholic products in S. cerevisiae.

A Free Amino Acid Diet Alleviates Colorectal Tumorigenesis through Modulating Gut Microbiota and Metabolites.

Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for cancer therapy effectiveness. This study explored the effects of a casein protein diet (CTL) versus a free amino acid (FAA)-based diet on CRC progression, gut microbiota, and metabolites using carcinogen-induced (AOM/DSS) and spontaneous genetically induced (ApcMin/+ mice) CRC mouse models. Comprehensive approaches including 16s rRNA gene sequencing, transcriptomics, metabolomics, and immunohistochemistry were utilized. We found that the FAA significantly attenuated CRC progression, evidenced by reduced colonic shortening and histopathological alterations compared to the CTL diet. Notably, the FAA enriched beneficial gut bacteria like Akkermansia and Bacteroides and reversed CRC-associated dysbiosis. Metabolomic analysis highlighted an increase in ornithine cycle metabolites and specific fatty acids, such as Docosapentaenoic acid (DPA), in FAA-fed mice. Transcriptomic analysis revealed that FAA up-regulated Egl-9 family hypoxia inducible factor 3 (Egln 3) and downregulated several cancer-associated pathways including Hippo, mTOR, and Wnt signaling. Additionally, DPA was found to significantly induce EGLN 3 expression in CRC cell lines. These results suggest that FAA modulate gut microbial composition, enhance protective metabolites, improve gut barrier functions, and inhibit carcinogenic pathways.

Diaphorobacter nitroreducens synergize with oxaliplatin to reduce tumor burden in mice with lung adenocarcinoma.

Lung adenocarcinoma (LADC) is the most common lung cancer and the leading cause of cancer-related deaths globally. Accumulating evidence suggests that the gut microbiota regulates the host response to chemotherapeutic drugs and can be targeted to reduce the toxicity of current chemotherapeutic agents. However, the effect of Diaphorobacter nitroreducens synergized with oxaliplatin on the gut microbiota and their impact on LADC have never been explored. This study aimed to evaluate the anti-cancer effects of D. nitroreducens, oxaliplatin, and their combined treatment on tumor growth in tumor-bearing mice. The composition of gut microbiota and the immune infiltration of tumors were evaluated by using 16S rRNA gene high-throughput sequencing and immunofluorescence, respectively. The inhibitory effect of the combination treatment with D. nitroreducens and oxaliplatin was significantly stronger than that of oxaliplatin alone in tumor-bearing mice. Furthermore, we observed that the combination treatment significantly increased the relative abundance of Lactobacillus and Akkermansia in the gut microbiota. Meanwhile, the combination treatment significantly increased the proportions of macrophage but decreased the proportion of regulatory T cells in the LADC tumor tissues of mice. These findings underscored the relationship between D. nitroreducens and the gut microbiota-immune cell-LADC axis, highlighting potential therapeutic avenues for LADC treatment. IMPORTANCE: Oxaliplatin is widely used as an effective chemotherapeutic agent in cancer treatment, but its side effects and response rate still need to be improved. Conventional probiotics potentially benefit cancer chemotherapy by regulating gut microbiota and tumor immune infiltration. This study was novel in reporting a more significant inhibitory effect of Diaphorobacter nitroreducens on lung adenocarcinoma (LADC) cells compared with common traditional probiotics and validating its potential as an adjuvant therapy for LADC chemotherapy in mice. This study investigated the impact of D. nitroreducens combined with oxaliplatin on the gut microbiota and immune infiltration of tumors as a potential mechanism to improve anticancer effects.

Constructing a Novel Amino Acid Metabolism Signature: A New Perspective on Pheochromocytoma Diagnosis, Immune Landscape, and Immunotherapy.

Pheochromocytoma/paraganglioma (PGPG) is a rare neuroendocrine tumor. Amino acid metabolism is crucial for energy production, redox balance, and metabolic pathways in tumor cell proliferation. This study aimed to build a risk model using amino acid metabolism-related genes, enhancing PGPG diagnosis and treatment decisions. We analyzed RNA-sequencing data from the PCPG cohort in the GEO dataset as our training set and validated our findings using the TCGA dataset and an additional clinical cohort. WGCNA and LASSO were utilized to identify hub genes and develop risk prediction models. The single-sample gene set enrichment analysis, MCPCOUNTER, and ESTIMATE algorithm calculated the relationship between amino acid metabolism and immune cell infiltration in PCPG. The TIDE algorithm predicted the immunotherapy efficacy for PCPG patients. The analysis identified 292 genes with differential expression, which are involved in amino acid metabolism and immune pathways. Six genes (DDC, SYT11, GCLM, PSMB7, TYRO3, AGMAT) were identified as crucial for the risk prediction model. Patients with a high-risk profile demonstrated reduced immune infiltration but potentially higher benefits from immunotherapy. Notably, DDC and SYT11 showed strong diagnostic and prognostic potential. Validation through quantitative Real-Time Polymerase Chain Reaction and immunohistochemistry confirmed their differential expression, underscoring their significance in PCPG diagnosis and in predicting immunotherapy response. This study's integration of amino acid metabolism-related genes into a risk prediction model offers critical clinical insights for PCPG risk stratification, potential immunotherapy responses, drug development, and treatment planning, marking a significant step forward in the management of this complex condition.

Protective Effect of the Polyphenol Ligustroside on Colitis Induced with Dextran Sulfate Sodium in Mice.

Dietary polyphenols are reported to alleviate colitis by interacting with gut microbiota which plays an important role in maintaining the integrity of the intestinal barrier. As a type of dietary polyphenol, whether ligustroside (Lig) could alleviate colitis has not been explored yet. Here, we aimed to determine if supplementation of ligustroside could improve colitis. We explored the influence of ligustroside intake with different dosages on colitis induced with dextran sulfate sodium (DSS). Compared to the DSS group, supplementation of ligustroside could reduce body weight (BW) loss, decrease disease activity indices (DAI), and relieve colon damage in colitis mice. Furthermore, ligustroside intake with 2 mg/kg could decrease proinflammatory cytokine concentrations in serum and increase immunoglobulin content and antioxidant enzymes in colon tissue. In addition, supplementation of ligustroside (2 mg/kg) could reduce mucus secretion and prevent cell apoptosis. Also, changes were revealed in the bacterial community composition, microbiota functional profiles, and intestinal metabolite composition following ligustroside supplementation with 2 mg/kg using 16S rRNA sequencing and non-targeted lipidomics analysis. In conclusion, the results showed that ligustroside was very effective in preventing colitis through reduction in inflammation and the enhancement of the intestinal barrier. Furthermore, supplementation with ligustroside altered the gut microbiota and lipid composition of colitis mice.

Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

Lactic acid fermentation of goji berries (Lycium barbarum) prevents acute alcohol liver injury and modulates gut microbiota and metabolites in mice.

Juice fermented with lactic acid bacteria (LAB) has received attention due to its health benefits, such as antioxidant and anti-inflammatory. Previous research on LAB-fermented goji juice mainly focused on exploring the changes in the metabolite profile and antioxidant activity in vitro, whereas the liver protection properties of LAB-fermented goji juice in vivo are still unknown. This study aimed to investigate the effects of Lacticaseibacillus paracasei E10-fermented goji juice (E10F), Lactiplantibacillus plantarum M-fermented goji juice (MF), Lacticaseibacillus rhamnosus LGG-fermented goji juice (LGGF) on preventing acute alcoholic liver injury with physiology, gut microbial, and metabolic profiles in mice. Compared with goji juice, E10F, MF, and LGGF enhanced the protective effect against liver injury by reducing serum alanine transaminase (ALT) levels, improving the hepatic glutathione (GSH) antioxidant system, and attenuating inflammation by decreasing the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß. Furthermore, E10F, MF, and LGGF increased intestinal integrity, restructured the gut microbiota including Bacteroides and Lactobacillus, and altered gut microbial metabolites including kyotorphin, indolelactic acid, and N-methylserotonin. Pretreatment of different LAB-fermented goji juice in mice showed significant differences in gut microbiota and metabolism. The correlation analysis demonstrated that the increase of Lactobacillus, indolelactic acid, and N-methylserotonin by E10F, MF, and LGGF was positively correlated with reduced inflammation and improved liver and gut function. Taken together, E10F, MF, and LGGF all have the potential to be converted into dietary interventions to combat acute alcoholic liver injury. It provided a reference for the study of the hepatoprotective effect of LAB-fermented goji juice.

CyHV-2 infection triggers mitochondrial-mediated apoptosis in GiCF cells by upregulating the pro-apoptotic gene ccBAX.

Apoptosis is a physiological cell death phenomenon, representing one of the fundamental physiological mechanisms for maintaining homeostasis in living organisms. Previous studies have observed typical apoptotic features in Carassius auratus gibelio caudal fin cell (GiCF) infected with Cyprinid herpesvirus 2 (CyHV-2), and found a significant up-regulation of ccBAX expression in these infected cells. However, the specific apoptotic mechanism involved remains unclear. In this study, we utilized the GiCF cell line to investigate the apoptotic mechanism during CyHV-2 infection. Immunofluorescence staining revealed translocation of ccBAX into mitochondria upon CyHV-2 infection. Flow cytometry analysis demonstrated that overexpression of ccBAX expedited virus-induced apoptosis, characterized by heightened mitochondrial depolarization, increased transcriptional levels of Cytochrome c (Cyto c) in both the cytoplasm and mitochondria, and augmented Caspase 3/7 enzyme activity. Bax inhibitor peptide V5 (BIP-V5), an inhibitor interfering with the function of Bax proteins, inhibited Bax-mediated apoptotic events through the mitochondrial pathway and attenuated apoptosis induced by CyHV-2. In this study, it was identified for the first time that CyHV-2 induces apoptosis via the mitochondrial pathway in GiCF cells, bridging an important gap in our understanding regarding cell death mechanisms induced by herpesvirus infections in fish species. These findings provide a theoretical basis for comprehending viral apoptotic regulation mechanisms and the prevention and control of cellular pathologies caused by CyHV-2 infection.

Analysis of the Current Status and Factors Influencing Compliance with Colonoscopic Monitoring After Endoscopic Surgery for Advanced Colorectal Adenoma.

Background: Advanced colorectal adenomas are at a risk of malignant transformation following endoscopic resection, and colonoscopic monitoring interval after polypectomy have been widely used. This study aims to investigate the prevailing state of compliance with postoperative colonoscopic surveillance among patients with advanced colorectal adenomas and its' influencing factors at Affiliated Hospital of Jiangnan University between November 2020 and April 2021. Methods: A retrospective analysis was conducted on patients who underwent endoscopic treatment for ACA at Affiliated Hospital of Jiangnan University from November 2020 to April 2021. Compliance with postoperative colonoscopic surveillance was assessed based on established guidelines. Factors such as sociodemographic features, medical histories, and health beliefs were analyzed to determine their influence on compliance. Univariate analysis, survival analysis, and multi-factor Cox regression analysis were used for statistical evaluation. Results: A total of 511 patients were included in the study. The compliance rate was found to be 43.2%. The univariate analysis indicated that factors such as gender, education level, work status, type of health insurance, place of residence, marital status, type of consultation, presence of gastrointestinal symptoms, number of polyps, and the maximum diameter of polyps significantly affected compliance. Multi-factor Cox regression analysis revealed that female gender, absence of gastrointestinal symptoms, outpatient endoscopic treatment, and solitary polyps were independent factors influencing compliance. Reasons for poor compliance included underestimating the severity of the disease, fear of colonoscopy, and procedural complexities. Conclusion: Patients with advanced colorectal adenomas had poor compliance with postoperative colonoscopy monitoring. Tailored health education programs should be designed, targeting women, outpatients undergoing endoscopic procedures, and patients with solitary polyps to enhance their compliance with colonoscopy monitoring.

Exploring the role of the disulfidptosis-related gene SLC7A11 in adrenocortical carcinoma: implications for prognosis, immune infiltration, and therapeutic strategies.

BACKGROUND: Disulfidptosis and the disulfidptosis-related gene SLC7A11 have recently attracted significant attention for their role in tumorigenesis and tumour management. However, its association with adrenocortical carcinoma (ACC) is rarely discussed. METHODS: Differential analysis, Cox regression analysis, and survival analysis were used to screen for the hub gene SLC7A11 in the TCGA and GTEx databases and disulfidptosis-related gene sets. Then, we performed an association analysis between SLC7A11 and clinically relevant factors in ACC patients. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of SLC7A11 and clinically relevant factors. Weighted gene coexpression analysis was used to find genes associated with SLC7A11. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the LinkedOmics database were used to analyse the functions of SLC7A11-associated genes. The CIBERSORT and Xcell algorithms were used to analyse the relationship between SLC7A11 and immune cell infiltration in ACC. The TISIDB database was applied to search for the correlation between SLC7A11 expression and immune chemokines. In addition, we performed a correlation analysis for SLC7A11 expression and tumour mutational burden and immune checkpoint-related genes and assessed drug sensitivity based on SLC7A11 expression. Immunohistochemistry and RT‒qPCR were used to validate the upregulation of SLC7A11 in the ACC. RESULTS: SLC7A11 is highly expressed in multiple urological tumours, including ACC. SLC7A11 expression is strongly associated with clinically relevant factors (M-stage and MYL6 expression) in ACC. SLC7A11 and the constructed nomogram can accurately predict ACC patient outcomes. The functions of SLC7A11 and its closely related genes are tightly associated with the occurrence of disulfidptosis in ACC. SLC7A11 expression was tightly associated with various immune cell infiltration disorders in the ACC tumour microenvironment (TME). It was positively correlated with the expression of immune chemokines (CXCL8, CXCL3, and CCL20) and negatively correlated with the expression of immune chemokines (CXCL17 and CCL14). SLC7A11 expression was positively associated with the expression of immune checkpoint genes (NRP1, TNFSF4, TNFRSF9, and CD276) and tumour mutation burden. The expression level of SLC7A11 in ACC patients is closely associated withcthe drug sensitivity. CONCLUSION: In ACC, high expression of SLC7A11 is associated with migration, invasion, drug sensitivity, immune infiltration disorders, and poor prognosis, and its induction of disulfidptosis is a promising target for the treatment of ACC.

Predicting Personalized Diets Based on Microbial Characteristics between Patients with Superficial Gastritis and Atrophic Gastritis.

BACKGROUND: gastritis is a common stomach disease with a high global incidence and can potentially develop into gastric cancer. The treatment of gastritis focuses on medication or diets based on national guidelines. However, the specific diet that can alleviate gastritis remains largely unknown. METHODS: we propose a microbiota-directed dietary strategy that investigates potential food factors using microbial exogenous metabolites. Given the current lack of understanding of the repeatable characteristics of gastric microbiota, we conducted a meta-analysis to identify the features of gastric bacteria. Local samples were collected as validation cohorts. Furthermore, RevEcoR was employed to identify bacteria's exogenous metabolites, and FooDB was used to retrieve foods that can target specific bacteria. RESULTS: Bacteroides, Weissella, Actinomyces, Atopobium, Oribacterium, Peptostreptococcus, and Rothia were biomarkers between superficial gastritis (SG) and atrophic gastritis (AG) (AG_N) without H. pylori infection, whereas Bacillus, Actinomyces, Cutibacterium, Helicobacter, Novosphingobium, Pseudomonas, and Streptococcus were signatures between SG and AG (AG_P) with H. pylori infection. According to the exogenous metabolites, adenosyloobalamin, soybean, common wheat, dates, and barley were regarded as potential candidates for AG_N treatment, while gallate was regarded as a candidate for AG_P treatment. CONCLUSIONS: this study firstly profiled the gastric microbiota of AG and SG with or without H. pylori and provided a recommended diet for global AG according to exogenous metabolites.

Akkermansia muciniphila Protects Against Antibiotic-Associated Diarrhea in Mice.

Probiotics are used to prevent antibiotic-associated diarrhea (AAD) via the restoration of the gut microbiota. However, the precise effects of Akkermansia muciniphila (Akk), which is a promising probiotics, on AAD are unknown. Here, AAD models were established via the administration of lincomycin and ampicillin with or without pasteurized Akk or Amuc_1100 treatment. A diffusion test revealed that Akk was susceptible to the majority of the antibiotics, such as ampicillin. These effects were confirmed by the reduced Akk abundance in AAD model mice. Pasteurized Akk or Amuc_1100 significantly decreased the diarrhea status score and colon injury of AAD model mice. Additionally, these treatments significantly decreased the relative abundance of Citrobacter at genus level and reshaped the metabolic function of gut microbiota. Notably, pasteurized Akk or Amuc_1100 significantly changed the serum metabolome of AAD model mice. In addition, pasteurized Akk or Amuc_1100 suppressed intestinal inflammation by upregulating the expression of GPR109A and SLC5A8 and downregulating the expression of TNFα, IFNγ, IL1ß, and IL6. Furthermore, they enhanced water and electrolyte absorption by upregulating AQP4, SLC26A3, and NHE3. Pasteurized Akk or Amuc_1100 also restored intestinal barrier function by ameliorating the downregulation of ZO-1, OCLN, CLDN4, and Muc2 in AAD model mice. In summary, optimizing intestinal health with pasteurized Akk or Amuc_1100 may serve as an approach for preventing AAD.

The identification of viral ribonucleotide reductase encoded by ORF23 and ORF141 genes and effect on CyHV-2 replication.

Introduction: Ribonucleotide reductase (RR) is essential for the replication of the double-stranded DNA virus CyHV-2 due to its ability to catalyze the conversion of ribonucleotides to deoxyribonucleotides, and is a potential target for the development of antiviral drugs to control CyHV-2 infection. Methods: Bioinformatic analysis was conducted to identify potential homologues of RR in CyHV-2. The transcription and translation levels of ORF23 and ORF141, which showed high homology to RR, were measured during CyHV-2 replication in GICF. Co-localization experiments and immunoprecipitation were performed to investigate the interaction between ORF23 and ORF141. siRNA interference experiments were conducted to evaluate the effect of silencing ORF23 and ORF141 on CyHV-2 replication. The inhibitory effect of hydroxyurea, a nucleotide reductase inhibitor, on CyHV-2 replication in GICF cells and RR enzymatic activity in vitro was also evaluated. Results: ORF23 and ORF141 were identified as potential viral ribonucleotide reductase homologues in CyHV-2, and their transcription and translation levels increased with CyHV-2 replication. Co-localization experiments and immunoprecipitation suggested an interaction between the two proteins. Simultaneous silencing of ORF23 and ORF141 effectively inhibited the replication of CyHV-2. Additionally, hydroxyurea inhibited the replication of CyHV-2 in GICF cells and the in vitro enzymatic activity of RR. Conclusion: These results suggest that the CyHV-2 proteins ORF23 and ORF141 function as viral ribonucleotide reductase and their function makes an effect to CyHV-2 replication. Targeting ribonucleotide reductase could be a crucial strategy for developing new antiviral drugs against CyHV-2 and other herpesviruses.

A Comparison of Single and Combined Schemes of Asia-Pacific Colorectal Screening, Faecal Immunochemical and Stool Deoxyribonucleic Acid Testing for Community Colorectal Cancer Screening.

Objective: To compare the screening efficacy of colonoscopy and pathologically confirmed single and combined Asia-Pacific colorectal screening (APCS), faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing protocols. Methods: From April 2021 to April 2022, 842 volunteers participated in primary colorectal cancer (CRC) screenings using APCS scoring, FIT and sDNA testing and 115 underwent a colonoscopy. One hundred high-risk participants were then identified from the results of both processes. The differences in the three CRC screening tests in combination with the colonoscopy pathology diagnostics were evaluated using Cochran's Q test, the Dunn-Bonferroni test and area under the receiver operating characteristic curve (AUC) value analysis. Results: Both FIT and sDNA testing demonstrated a 100% performance in detecting CRC. For advanced adenoma, the sensitivity of the FIT + sDNA test scheme (double positive) was 29.2%, and the sensitivities of the combined FIT + sDNA test and APCS scoring + sDNA test schemes were 62.5% and 95.8%, respectively. The FIT + sDNA testing kappa value of advanced colorectal neoplasia was 0.344 (p = 0.011). The sensitivity for nonadvanced adenoma of the APCS score + sDNA test scheme was 91.1%. In terms of positive results, the sensitivity of the APCS score + FIT + sDNA detection protocol was significantly higher than that of the APCS score, FIT, sDNA detection, and FIT + sDNA detection methods (adjusted p < 0.001, respectively). For the FIT + sDNA test, the kappa value was 0.220 (p = 0.015) and the AUC was 0.634 (p = 0.037). The specificity of the FIT + sDNA test scheme was 69.0%. Conclusion: The FIT + sDNA test scheme demonstrated superior diagnostic efficacy, and the combined APCS score + FIT + sDNA test scheme demonstrated remarkable improvements in CRC screening efficiency and sensitivity for detecting positive lesions.

Diversity and Comparison of Intestinal Desulfovibrio in Patients with Liver Cirrhosis and Healthy People.

Desulfovibrio belongs to Sulfate-reducing bacteria (SRB), which are widely present in anaerobic environments, including the human gut. Desulfovibrio has been associated with many human diseases, including chronic liver disease. However, the characteristics and difference of Desulfovibrio from fecal samples of healthy volunteers (HV) and patients with liver cirrhosis (LC) have not been fully elucidated. Here, we isolated Desulfovibrio from the feces of 6 HV and 9 LC, and 88 Desulfovibrio strains were obtained. In the feces of HV, 55% of isolated strains were D. desulfuricans, followed by D. intestinalis (15%), D. simplex (11%), D. piger (9%), D. legallii (4%), Cupidesulfovibrio oxamicus (4%) and D. fairfieldensis (2%). However, only D. desulfuricans (60%) and C. oxamicus (40%) were isolated from fecal samples of patients with LC. Our results suggest that there was a significant difference in the desulfurization ability and the H2S production ability of different Desulfovibrio. Desulfovibrio. Furthermore, we found that Desulfovibrio isolated from the patients with LC generally had a higher hydrogen sulfide production capacity, gastrointestinal tolerance, and levels of antibiotic resistance than the same species isolated from HV. Our findings suggested that Desulfovibrio may be associated with the occurrence and development of liver cirrhosis.