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Lactobacillus delbrueckii ssp. bulgaricus M58 (M58) and Streptococcus thermophilus S10 (S10) are 2 dairy starter strains known for their favorable fermentation characteristics. Therefore, this research aimed to study the effects of 1-d low-temperature ripening on the physicochemical properties and metabolomics of fermented milk. Initially, the performance of single (M58 or S10) and dual (M58+S10) strain fermentation was assessed, revealing that the M58+S10 combination resulted in a shortened fermentation time, a stable gel structure, and desirable viscosity, suggesting positive strain interactions. Subsequently, non-targeted metabolomics analyses using LC-MS and GC-MS were performed to comparatively analyze M58+S10 fermented milk samples collected at the end of fermentation and after 1-d low-temperature ripening. The results showed a significant increase in almost all small peptides and dodecanedioic acid in the samples after one day of ripening, while there was a substantial decrease in indole and amino acid metabolites. Moreover, notable increases were observed in high-quality flavor compounds, such as geraniol, delta-nonalactone, 1-hexanol,2-ethyl-, methyl jasmonate, and undecanal. This study provides valuable insights into the fermentation characteristics of the dual bacterial starter consisting of M58 and S10 strains and highlights the specific contribution of the low-temperature ripening step to the overall quality of fermented milk.
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Bifidobacterium pseudocatenulatum is a prevalent gut microbe in humans of all ages and plays a crucial role in host health. However, its adaptive evolutionary characteristics remain poorly understood. This study analyzed the genome of 247 B. pseudocatenulatum isolates from Chinese, Vietnamese, Japanese and other region populations using population genomics and functional genomics. Our findings revealed high genetic heterogeneity and regional clustering within B. pseudocatenulatum isolates. Significant differences were observed in genome characteristics, phylogeny, and functional genes. Specifically, Chinese and Vietnamese isolates exhibited a higher abundance of genes involved in the metabolism of plant-derived carbohydrates (GH13, GH43, and GH5 enzyme families), aligning with the predominantly vegetable-, wheat- and fruit-based diets of these populations. Additionally, we found widespread transmission of antibiotic resistance genes (tetO and tetW) through mobile genetic elements, such as genomic islands (GIs), resulting in substantial intra-regional differences. Our findings highlight distinct adaptive evolution in B. pseudocatenulatum driven by gene specialization, possibly in response to regional variations in diet and lifestyle. This study sheds light on bifidobacteria colonization mechanisms in the host gut. IMPORTANCE: Gut microbiota, as a key link in the gut-brain axis, helps to maintain the health of the organism, among which, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum) is an important constituent member of the gut microbiota, which plays an important role in maintaining the balance of gut microbiota. The probiotic properties of B. pseudocatenulatum have been widely elaborated, and in order to excavate its evolutionary features at the genomic level, here we focused on the genetic background and evolutionary mechanism of the B. pseudocatenulatum genomes isolated from the intestinal tracts of different populations. Ultimately, based on the phylogenetic tree, we found that B. pseudocatenulatum has high genetic diversity and regional clustering phenomenon, in which plant-derived carbohydrate metabolism genes (GH13, GH43, GH5) showed significant regional differences, and this genetic differentiation drove the adaptive evolution, which likely shaped by diet and lifestyle.
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Bifidobacterium pseudocatenulatum , Microbioma Gastrointestinal , Genoma Bacteriano , Filogenia , Microbioma Gastrointestinal/genética , Humanos , Bifidobacterium pseudocatenulatum/genética , Bifidobacterium pseudocatenulatum/metabolismo , Variación Genética , Genómica , DietaRESUMEN
Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate symptoms of diarrhea. This randomized, double-blind, placebo-controlled trial evaluates the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) strain in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention period lasts for 28 days, followed by a 14-day post-intervention period. Participants are randomized into the P9 (n = 93) and placebo (n = 96) groups, with 170 individuals completing the double-blind intervention phase (n = 85 per group). The primary endpoint is the diarrhea symptom severity score. Both intention-to-treat (n = 189) and per-protocol (n = 170) analyses reveal a modest yet statistically significant reduction in diarrhea severity compared to the placebo group (20.0%, P = 0.050; 21.4%, P = 0.048, respectively). In conclusion, the results of this study support the use of probiotics in managing chronic diarrhea in young adults. However, the lack of blood parameter assessment and the short intervention period represent limitations of this study.
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Diarrea , Probióticos , Humanos , Diarrea/microbiología , Diarrea/terapia , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Método Doble Ciego , Masculino , Adulto Joven , Adulto , Femenino , Enfermedad Crónica , Resultado del Tratamiento , Lactobacillus plantarum , AdolescenteRESUMEN
Breast milk naturally contains lactic acid bacteria, but their precise origin remains a subject of debate. In this study, we utilized a rat mastitis animal model to investigate the potential of a breast milk-derived probiotic strain, Lacticaseibacillus rhamnosus Probio-M9, in alleviating mastitis and enhancing the efficacy of antibiotic treatment. Through histopathological analysis of mammary tissue, we observed that Probio-M9 effectively relieved mastitis, mitigated inflammation, and improved the response to antibiotic treatment. Metagenomic analysis further revealed that Probio-M9 enhanced interactions among gut microbes, accompanied by an increase in the relative abundance of Ruminococcaceae and the regulation of specific genes and carbohydrate-active enzymes, subsequently impacting host immunity. Additionally, an intriguing finding was the translocation of live Probio-M9 from the gut to the mammary tissue only during bacterial mastitis and lactation, likely facilitated through lymphatic circulation. These findings advance our understanding of the intricate gut-mammary axis and provide valuable insights into the potential health benefits of probiotic interventions.
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Our meta-analysis aimed to assess the effectiveness of probiotics in weight loss and glucose and lipid metabolism in overweight or obese women. PubMed, EMBASE, Cochrane Library, and Web of Science were used from inception until March 2024 to identify randomized controlled trials (RCT's) literature. Finally, 11 RCTs were included. Following critical appraisal, a meta-analysis was conducted using the fixed effects model and the random effects model found that probiotic consumption significantly decreased waist circumference (WC) (SMD = -0.39 cm, 95% CI: -0.60, -0.18 cm, P < 0.00001, I2 = 33%), insulin (SMD = -0.45 mcU/ml; 95% CI: -0.72, -0.18 mcU/ml; P = 0.04, I2 = 40%) and low-density lipoprotein cholesterol (LDL-C) levels (SMD = -0.51 mmol/L; 95% CI: -0.92, -0.11 mmol/L; P = 0.02, I2 = 75%) in overweight or obese women. Moreover, subgroup analyses revealed that the effects of probiotic supplementation were significantly influenced by the intervention duration and diet and/or exercise intervention. This meta-analysis suggested that probiotic supplementation has a moderate and statistically significant effect on weight loss and glucose and lipid metabolism in overweight and obese women.
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Broad-spectrum antibacterial drugs often lack specificity, leading to indiscriminate bactericidal activity, which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration. In this study, we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure-function relationship through one-factor modification. SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S. aureus. Moreover, SFK2 showed excellent biocompatibility in mice and piglet, and demonstrated significant therapeutic efficacy against S. aureus infection. In conclusion, our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S. aureus, providing a theoretical basis for developing targeted antimicrobial peptides.
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PURPOSE: It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). METHODS: We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. RESULTS: There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349-4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397-6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393-3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022-8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE. CONCLUSIONS: Our results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.
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Enfermedades Cardiovasculares , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Masculino , Femenino , Anciano , Estudios Prospectivos , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/mortalidad , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Apnea Obstructiva del Sueño/mortalidad , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Anciano de 80 o más Años , Causas de Muerte/tendencias , Factores de RiesgoRESUMEN
Circulating cell-free DNA (cfDNA) in the peripheral blood is a promising biomarker for cancer diagnosis and prognosis. Somatic mutations identified in cancers have been used to detect therapeutic targets for clinical transformation and individualize drug selection, while germline variants can predict a patient's risk of developing cancer and drug sensitivity. However, no platform has been developed to analyze, calculate, integrate, and friendly visualize these pan-cancer cfDNA mutations deeply. In this work, we performed panel sequencing encompassing 1,115 cancer-related genes across 16,659 cancer patients, spanning 27 cancer types. We detected 496 germline variants in leukocytes and 11,232 somatic mutations in the cfDNA of all patients. CPGV (Cancer Peripheral blood Gene Variations), a database constructed from this dataset, is the first pan-cancer cfDNA database that encompasses somatic mutations, germline variants, and further comparative analyses of mutations across different cancer types. It bears great promise to serve as a valuable resource for cancer research.
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Neoplasias , Humanos , Neoplasias/genética , Neoplasias/sangre , Mutación , Mutación de Línea Germinal , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Variación Genética , Bases de Datos GenéticasRESUMEN
BACKGROUND: Gut microbes play an important role in the growth and health of neonatal piglets. Probiotics can promote the healthy growth of neonatal piglets by regulating their gut microbes. The study investigated the effects of spraying Lactiplantibacillus plantarum P-8 (L. plantarum P-8) fermentation broth on the growth performance and gut microbes of neonatal piglets. RESULTS: The animals were randomly divided into probiotics groups (109 neonatal piglets) and control groups (113 neonatal piglets). The probiotics group was sprayed with L. plantarum P-8 fermented liquid from 3 day before the expected date of the sow to the 7-day-old of piglets, while the control group was sprayed with equal dose of PBS. Average daily gain (ADG), immune and antioxidant status and metagenome sequencing were used to assess the changes in growth performance and gut microbiota of neonatal piglets. The results showed that L. plantarum P-8 treatment significantly improved the average daily gain (P < 0.05) of neonatal piglets. L. plantarum P-8 increased the activities of CAT and SOD but reduced the levels of IL-2 and IL-6, effectively regulating the antioxidant capacity and immunity in neonatal piglets. L. plantarum P-8 adjusted the overall structure of gut microflora improving gut homeostasis to a certain extent, and significantly increased the relative abundance of gut beneficial bacteria such as L. mucosae and L. plantarum. CONCLUSION: Spraying L. plantarum P-8 can be a feasible and effective probiotic intervention not only improving the growth of neonatal piglets, regulating the antioxidant capacity and immunity of neonatal piglets, but also improving the gut homeostasis to a certain extent.
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Animales Recién Nacidos , Microbioma Gastrointestinal , Probióticos , Animales , Probióticos/administración & dosificación , Probióticos/farmacología , Porcinos , Microbioma Gastrointestinal/efectos de los fármacos , Lactobacillus plantarum , Fermentación , Antioxidantes/metabolismo , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Heces/microbiologíaRESUMEN
BACKGROUND: To investigate the sex-based heterogeneity of immune microenvironmental feature and its impact on the response to first-line PD-1 blockade plus chemotherapy in patients with driver-negative advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 439 patients with advanced NSCLC treated with first-line PD-1 blockade plus chemotherapy or chemotherapy were identified. Differences in clinical outcomes between female and male patients were determined using Kaplan-Meier curves. Neoantigen burden and five immune microenvironmental markers expression including PD-L1, CD4, CD8, FOXP3, and CD68 were compared between two groups. RESULTS: Of 175 eligible patients, 89 received PD-1 blockade plus chemotherapy and 86 received first-line chemotherapy. Forty five were women (25.7%) and 130 were men (74.3%). Female patients received first-line PD-1 blockade in combination with chemotherapy had dramatically better ORR (85.2% vs. 53.2%; p = 0.009), PFS (23.7 vs. 7.3 months; p = 0.013), and OS (46.2 vs. 20.0 months; p = 0.004) than males. Treatment outcomes were similar between females and males in chemotherapy group. Multivariate analyses showed that sex was the independent prognostic factor for patients received PD-1 blockade combined with chemotherapy. Although female patients had significantly lower tumor mutational and neoantigen burden than males, pretreatment tumor tissues of female patients had markedly higher CD4, CD4/FOXP3, and CD4/FOXP3/PD-L1 expression level than male patients. CONCLUSIONS: Female patients with untreated advanced or metastatic NSCLC would derive a larger benefit from PD-1 blockade in combination with chemotherapy than males. The biological significances of heterogeneity of tumor immune microenvironmental features between them need further investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Microambiente Tumoral/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Anciano , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factores Sexuales , Adulto , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano de 80 o más Años , Biomarcadores de Tumor , Estudios Retrospectivos , Factores de Transcripción ForkheadRESUMEN
Correction for 'Administering Lactiplantibacillus fermentum F6 decreases intestinal Akkermansia muciniphila in a dextran sulfate sodium-induced rat colitis model' by Qiuwen He et al., Food Funct., 2024, 15, 5882-5894, https://doi.org/10.1039/d4fo00462k.
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Probiotics are increasingly used as starter cultures to produce fermented dairy products; however, few studies have investigated the role of probiotics in milk fermentation metabolism. The current study aimed to investigate whether adding Bifidobacterium animalis ssp. lactis Probio-M8 (Probio-M8) as a starter culture strain could improve milk fermentation by comparing the physicochemical characteristics and metabolomes of fermented milks produced by a commercial starter culture with and without Probio-M8. Our results showed that adding Probio-M8 shortened the milk fermentation time and improved the fermented milk texture and stability. Metabolomics analyses revealed that adding Probio-M8 affected mostly organic acid, AA, and fatty acid metabolism in milk fermentation. Targeted quantitative analyses revealed significant increases in various metabolites related to the sensory quality, nutritive value, and health benefits of the probiotic fermented milk, including 5 organic acids (acetic acid, lactic acid, citric acid, succinic acid, and tartaric acid), 5 EAA (valine, arginine, leucine, isoleucine, and lysine), glutamic acid, and 2 essential fatty acids (α-linolenic acid and docosahexaenoic acid). Thus, applying probiotics in milk fermentation is desirable. This study has generated useful information for developing novel functional dairy products.
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Bifidobacterium animalis , Fermentación , Leche , Probióticos , Bifidobacterium animalis/metabolismo , Animales , Leche/química , Productos Lácteos Cultivados/microbiologíaRESUMEN
Traditional fermented milks are produced through an inoculation process that involves the deliberate introduction of microorganisms that have been adapted and perpetuated across successive generations. However, the changes in the microbiota of traditional fermented milk during long-term inoculation fermentation in a laboratory environment remain unclear. In this study, we collected 5 samples of traditional fermented milk samples from 5 different counties in Tibet (3 kurut products) and Xinjiang (2 tarag products) of China, which served as starter cultures for a 9-mo continuous inoculation fermentation experiment. We analyzed the inter- and intra-population variations in the microbial communities of the collected samples, representing their macrodiversity and microdiversity, using shotgun metagenomic sequencing. Across all samples, we obtained a total of 186 high-quality metagenomic-assembled genomes, including 7 genera and 13 species with a relative abundance of more than 1%. The majority of these genomes were annotated as Lactobacillus helveticus (60.46%), Enterococcus durans (9.52%), and Limosilactobacillus fermentum (6.23%). We observed significant differences in species composition and abundance among the 5 initial inoculants. During the long-term inoculation fermentation, we found an overall increasing trend in species diversity, composition, and abundances of carbohydrate metabolism module-encoding genes in the fermented milk bacterial metagenome, while the fermented milk virome exhibited a relatively narrow range of variation. Lactobacillus helveticus, a dominant species in traditional fermented milk, displayed high stability during the long-term inoculation fermentation. Our study provides valuable insights for the industrial production of traditional fermented milk.
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Probiotics are increasingly used to manage gut dysbiosis-related conditions due to their robust ability to manipulate the gut microbial community. However, few studies have reported that probiotics can specifically modulate individual gut microbes. This study demonstrated that administering the probiotic, Lactiplantibacillus fermentum F6, could ameliorate dextran sulfate sodium-induced colitis in a rat model, evidenced by the decreases in the disease activity index score, histopathology grading, and serum pro-inflammatory cytokine levels, as well as the increase in the serum anti-inflammatory cytokine levels. Shotgun metagenomics revealed that the fecal metagenomic of colitis rats receiving the probiotic intervention contained substantially fewer Akkermansia muciniphila than the dextran sulfate sodium group. Thus, the probiotic mechanism might be exerted by reducing specific gut microbial species associated with disease pathogenesis. A new paradigm for designing probiotics that manage diseases through direct and precise manipulation of gut microbes has been provided through this study.
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Akkermansia , Colitis , Microbioma Gastrointestinal , Limosilactobacillus fermentum , Probióticos , Animales , Masculino , Ratas , Colitis/inducido químicamente , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Disbiosis/microbiología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Limosilactobacillus fermentum/fisiología , Probióticos/farmacología , Probióticos/administración & dosificación , Ratas Sprague-DawleyRESUMEN
Post-weaning diarrhea (PWD) is a globally significant threat to the swine industry. Historically, antibiotics as well as high doses of zinc oxide and copper sulfate have been commonly used to control PWD. However, the development of bacterial resistance and environmental pollution have created an interest in alternative strategies. In recent years, the research surrounding these alternative strategies and the mechanisms of piglet diarrhea has been continually updated. Mechanically, diarrhea in piglets is a result of an imbalance in intestinal fluid and electrolyte absorption and secretion. In general, enterotoxigenic Escherichia coli (ETEC) and diarrheal viruses are known to cause an imbalance in the absorption and secretion of intestinal fluids and electrolytes in piglets, resulting in diarrhea when Cl- secretion-driven fluid secretion surpasses absorptive capacity. From a perspective of feedstuffs, factors that contribute to imbalances in fluid absorption and secretion in the intestines of weaned piglets include high levels of crude protein (CP), stimulation by certain antigenic proteins, high acid-binding capacity (ABC), and contamination with deoxynivalenol (DON) in the diet. In response, efforts to reduce CP levels in diets, select feedstuffs with lower ABC values, and process feedstuffs using physical, chemical, and biological approaches are important strategies for alleviating PWD in piglets. Additionally, the diet supplementation with additives such as vitamins and natural products can also play a role in reducing the diarrhea incidence in weaned piglets. Here, we examine the mechanisms of absorption and secretion of intestinal fluids and electrolytes in piglets, summarize nutritional strategies to control PWD in piglets from the perspective of feeds, and provide new insights towards future research directions.
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BACKGROUND & AIMS: Inflammatory bowel disease is associated with carcinogenesis, which limits the prognosis of the patients. The local expression of proteinases and proteinase-activated receptor 1 (PAR1) increases in inflammatory bowel disease. The present study investigated the therapeutic effects of PAR1 antagonism on colitis-associated carcinogenesis. METHODS: A colitis-associated carcinogenesis model was prepared in mice by treatment with azoxymethane (AOM) and dextran sulfate sodium (DSS). PAR1 antagonist E5555 was administered in long- and short-term protocol, starting on the day of AOM injection and 1 week after completing AOM/DSS treatment, respectively. The fecal samples were collected for metagenome analysis of gut microbiota. The intestinal myofibroblasts of the Crohn's disease patients were used to elucidate underlying cellular mechanisms. Caco-2 cells were used to investigate a possible source of PAR1 agonist proteinases. RESULTS: AOM/DSS model showed weight loss, diarrhea, tumor development, inflammation, fibrosis, and increased production of inflammatory cytokines. The ß-diversity, but not α-diversity, of microbiota significantly differed between AOM/DSS and control mice. E5555 alleviated these pathological changes and altered the microbiota ß-diversity in AOM/DSS mice. The thrombin expression was up-regulated in tumor and non-tumor areas, whereas PAR1 mRNA expression was higher in tumor areas compared with non-tumor areas. E5555 inhibited thrombin-triggered elevation of cytosolic Ca2+ concentration and ERK1/2 phosphorylation, as well as IL6-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in intestinal myofibroblasts. Caco-2 cell-conditioned medium contained immunoreactive thrombin, which cleaved the recombinant protein containing the extracellular domain of PAR1 at the thrombin cleavage site. CONCLUSIONS: PAR1 antagonism is proposed to be a novel therapeutic strategy for treatment of inflammatory bowel disease and its associated carcinogenesis.
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Azoximetano , Sulfato de Dextran , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Receptor PAR-1 , Animales , Receptor PAR-1/metabolismo , Receptor PAR-1/antagonistas & inhibidores , Humanos , Ratones , Células CACO-2 , Sulfato de Dextran/toxicidad , Azoximetano/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Colitis/complicaciones , Colitis/inducido químicamente , Colitis/patología , Colitis/tratamiento farmacológico , Carcinogénesis/efectos de los fármacos , Carcinogénesis/patología , Factor de Transcripción STAT3/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patología , Miofibroblastos/efectos de los fármacos , Neoplasias Asociadas a Colitis/patología , Neoplasias Asociadas a Colitis/microbiología , Neoplasias Asociadas a Colitis/tratamiento farmacológico , Neoplasias Asociadas a Colitis/inmunología , Trombina/metabolismo , Ratones Endogámicos C57BL , Enfermedad de Crohn/patología , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/microbiología , Enfermedad de Crohn/inducido químicamenteRESUMEN
High protein and fiber diets are becoming increasingly popular for weight loss; however, the benefits or risks of high protein and fiber diets with a normal calorie level for healthy individuals still need to be elucidated. In this study, we explored the role and mechanisms of long-term high protein and/or konjac glucomannan diets on the metabolic health of healthy mouse models. We found that high konjac glucomannan contents improved the glucose tolerance of mice and both high protein and high konjac glucomannan contents improved the serum lipid profile but increased the TNF-α levels. In the liver, high dietary protein contents reduced the expression of the FASN gene related to fatty acid synthesis. Interactions of dietary protein and fiber were shown in the signaling pathways related to lipid and glucose metabolism of the liver and the inflammatory status of the colon, wherein the high protein and high konjac glucomannan diet downregulated the expression of the SREBF1 and FXR genes in the liver and downregulated the expression of TNF-α genes in the colon compared to the high protein diet. High konjac glucomannan contents reduced the colonic secondary bile acid levels including DCA and LCA; this was largely associated with the changed microbiota profile and also contributed to improved lipid and glucose homeostasis. In conclusion, high protein diets improved lipid homeostasis and were not a risk to metabolic health, while high fiber diets improved glucose and lipid homeostasis by modulating colonic microbiota and bile acid profiles, and a high protein diet supplemented with konjac glucomannan might improve hepatic lipid homeostasis and colonic inflammation in healthy mouse models through long-term intervention.
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Ácidos y Sales Biliares , Colon , Microbioma Gastrointestinal , Glucosa , Metabolismo de los Lípidos , Mananos , Ratones Endogámicos C57BL , Animales , Mananos/farmacología , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ácidos y Sales Biliares/metabolismo , Colon/metabolismo , Colon/microbiología , Glucosa/metabolismo , Proteínas en la Dieta/metabolismo , Proteínas en la Dieta/farmacología , Hígado/metabolismo , Fibras de la Dieta/farmacología , Fibras de la Dieta/metabolismoRESUMEN
(1) Background: Bifidobacterium plays a pivotal role within the gut microbiota, significantly affecting host health through its abundance and composition in the intestine. Factors such as age, gender, and living environment exert considerable influence on the gut microbiota, yet scant attention has been directed towards understanding the specific effects of these factors on the Bifidobacterium population. Therefore, this study focused on 98 adult fecal samples to conduct absolute and relative quantitative analyses of bifidobacteria. (2) Methods: Using droplet digital PCR and the PacBio Sequel II sequencing platform, this study sought to determine the influence of various factors, including living environment, age, and BMI, on the absolute content and biodiversity of intestinal bifidobacteria. (3) Results: Quantitative results indicated that the bifidobacteria content in the intestinal tract ranged from 106 to 109 CFU/g. Notably, the number of bifidobacteria in the intestinal tract of the school population surpassed that of the off-campus population significantly (p = 0.003). Additionally, the group of young people exhibited a significantly higher count of bifidobacteria than the middle-aged and elderly groups (p = 0.041). The normal-weight group displayed a significantly higher bifidobacteria count than the obese group (p = 0.027). Further analysis of the relative abundance of bifidobacteria under different influencing factors revealed that the living environment emerged as the primary factor affecting the intestinal bifidobacteria structure (p = 0.046, R2 = 2.411). Moreover, the diversity of bifidobacteria in the intestinal tract of college students surpassed that in the out-of-school population (p = 0.034). This was characterized by a notable increase in 11 strains, including B. longum, B. bifidum, and B. pseudolongum, in the intestinal tract of college students, forming a more intricate intestinal bifidobacteria interaction network. (4) Conclusions: In summary, this study elucidated the principal factors affecting intestinal bifidobacteria and delineated their characteristics of intestinal bifidobacteria in diverse populations. By enriching the theory surrounding gut microbiota and health, this study provides essential data support for further investigations into the intricate dynamics of the gut microbiota.
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Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.