Intestinal Metabolism Research Articles

Intestinal Lactobacillus murinus-derived small RNAs target porcine polyamine metabolism

Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal Lactobacillus murinus-derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases.

ERICH4 is not involved in the assembly and secretion of intestinal lipoproteins

Background and AimsThe small intestine plays a central role in lipid metabolism, most notably the uptake of dietary fats that are packaged into chylomicrons and secreted into the circulation for utilisation by peripheral tissues. While microsomal triglyceride transfer protein (MTP) is known to play a key role in this pathway, the intracellular assembly, trafficking, and secretion of chylomicrons is incompletely understood. Methods and ResultsUsing human transcriptome datasets to find genes co-regulated with MTTP, we identified ERICH4 as a top hit. The gene encodes for glutamate-rich protein 4, a protein of unknown function. REACTOME gene-function prediction tools indicated that ERICH4 is involved in intestinal lipid metabolism. In addition, GWAS data point to a strong relationship between ERICH4 and plasma lipids. To validate ERICH4 as a lipid gene, we generated whole-body Erich4 knockout (Erich4-/-) mice. ERICH4 deficiency, however, did not result in changes in body weight and composition, food intake, circulating plasma lipids, energy absorption and excretion, and tissue weights compared to controls. Additionally, there were no morphological abnormalities seen in the small intestine. Challenging mice with a high-fat diet did not give rise to a phenotype either. ConclusionsDespite prediction tools indicating ERICH4 as a strong candidate gene in intestinal lipid metabolism, we here show that ERICH4 does not play a role in intestinal lipid metabolism in mice. It remains to be established whether ERICH4 plays a role in human lipid metabolism.

Interaction between energy level and starch: fat ratio on intestinal energy metabolism of layer pullets

During the growing period, the gastrointestinal tract of layer pullets is not yet well developed and may be susceptible to dietary energy level. The energy level and composition might impact the intestinal energy metabolism of layer pullets. To test this hypothesis, a total of 480 “Jing Tint 6” layer pullets were used in an 8-week study and allocated to 4 groups, each consisting of 8 replicates, with 15 birds per replicate. Pullets were treated with low or high starch: fat ratios (LS, 10:1; HS, 20:1) in a 2 × 2 factorial arrangement with regular energy (RE, 11.85 and 11.68 MJ/kg for birds from 6 to 10 weeks of age and 11 to 14 weeks of age, respectively) or low energy (LE, 0.55 MJ/kg lower than RE) levels. A significant interaction (P < 0.05) showed that HS increased glandular stomach weight and the jejunal villus length to crypt depth ratio (VCR) in LE diets, but decreased these parameters in RE diets. Dietary energy reduction impaired energy metabolism in the ileum (P < 0.05) mainly via decreasing the gene expression of enzymes involved in the tricarboxylic acid (TCA) cycle (α-ketoglutarate dehydrogenase complex [α-KGDH]; isocitrate dehydrogenase (NAD (+)) [IDH] catalytic; citrate synthase [CS]) and adenosine triphosphate (ATP) synthesis, reducing contents of phosphoenolpyruvate (PEP) and adenylate energy charges (AEC) and down-regulating the adenosine monophosphate-activated protein kinase (AMPK) pathway. HS stimulated AMPKα phosphorylation, increased protein abundance of peroxisome proliferator activated-receptor gamma coactivator 1α (PGC1α) and improved contents of amino acids (aspartate, glutamate, glutamine, alanine and threonine) and malate in the ileum regardless of energy levels (P < 0.05). By an interaction (P < 0.05), the transition from LS to HS diets up-regulated ileal gene expression of AMPKα1 and decreased content of adenosine monophosphate (AMP), accompanied by higher AEC but only in birds fed with LE diets. Collectively, these results suggest that low energy feeding may not be enough for maintaining intestinal energy homeostasis in layer pullets and emphasizes the importance of a relatively high starch: fat ratio in restoring energy metabolism in the ileum.

Xiaobugan decoction prevents CCl4-induced acute liver injury by modulating gut microbiota and hepatic metabolism

BackgroundThe liver plays a crucial role in detoxification and metabolism. When its capacity to metabolize foreign substances is exceeded, it can lead to acute liver injury (ALI). Therefore, preventing liver disease and maintaining daily liver health are of utmost importance. Xiaobugan Decoction (XBGD), a traditional Chinese medicine (TCM) formula, is recorded in ‘Fuxingjue’, is used in folk practice to promote liver health and regulate respiration. However, the hepatoprotective mechanisms of XBGD remained unclear. PurposeWe investigated the prophylactic and hepatoprotective effects of XBGD and explored its related molecular mechanisms using a mouse model of carbon tetrachloride (CCl4)-induced ALI. Study design and methodsXBGD composition was determined using analytical methods, and the main compounds were identified using ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) and high-performance liquid chromatography (HPLC). A CCl4-induced L02 cell injury model was employed to explore the protective effects of XBGD on liver cells, and a CCl4-induced ALI mouse model was used to investigate the hepatoprotective effects of XBGD. ResultsCellular experiments demonstrated that XBGD had a protective function against L02 cell damage by increasing cell viability, restoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD) levels, reducing malondialdehyde (MDA) content, and improving mitochondrial membrane potential (ΔΨm). In the mouse ALI model, XBGD prevented ALI by reducing ALT, AST, and alkaline phosphatase (ALP) levels and inhibiting oxidative stress. Quantitative real-time polymerase chain reaction (qPCR), immumohistochemical staining and western blotting results revealed that XBGD exerted hepatoprotective effects by reducing inflammatory responses and inhibiting cell apoptosis. Furthermore, 1H-NMR metabolomics indicated that XBGD regulates hepatic and intestinal metabolism, whereas 16S rDNA sequencing demonstrated the regulatory effects of XBGD on the gut microbiota. Correlation analysis highlighted the close relationship among gut microbiota, metabolites, and ALI indicators. ConclusionsXBGD is a promising TCM for the prevention of CCl4-induced ALI via regulation of microbiota and metabolism. This study provides a new perspective on the development of hepatoprotective measures and the prevention of liver disease in daily life.

Fructo-oligosaccharides promote butyrate production over citrus pectin during in vitro fermentation by colonic inoculum from pig

ObjectivesFructo-oligosaccharide (FOS) and citrus pectin (CP) are soluble fibers with different chemical composition. However, their fermentation pattern in large intestine remains unclear. MethodsAn in vitro batch fermentation using colonic digesta from pigs as inoculum was employed to investigate the fermentation dynamics of FOS and CP. The monosaccharides and SCFAs contents were assayed by High-Performance Liquid Chromatography and Gas Chromatography, respectively. And the microbiota community was assessed by 16S rRNA gene high-throughput sequencing. ResultsThe decline of monosaccharides in both substrates after 6 h, especially to a neglected level in FOS. FOS showed higher abundances of butyrate-producing bacteria such as Eubacterium rectale, Roseburia faecis and Coprococcus comes and butyrate compared to CP. CP stimulated the growth of pectinolytic microbe Lachnospira pectinoschiza, succinate-producing bacteria Succinivibrio dextrinosolvens, succinate-utilizing bacteria Phascolarctobacterium succinatutens and the production of acetate and propionate compared to FOS. Moreover, the relative abundances of key enzymes (e.g. butyrate kinase) involving in butyrate formation via the butyrate kinase route were upregulated in the FOS group. And the key enzymes (e.g. acetyl-CoA synthetase) associated with propionate production through the succinate pathway were upregulated in the CP group. ConclusionsFOS was preferred to ferment by butyrate-producing bacteria to yield a higher level of butyrate via the butyrate kinase pathway, while CP enhanced the cross-feeding of succinate-producing and succinate-utilizing bacteria to form propionate through the succinate pathway. These findings deepen our understanding on the fermentation characteristics of the soluble fibers, and also provide guidelines for fiber choice in precisely modulating the microbial composition and metabolism in large intestine.

Safflower dietary fiber alleviates functional constipation in rats via regulating gut microbiota and metabolism

A functional constipation rat model was established by loperamide hydrochloride (LOP), and then safflower dietary fiber (SDF) was supplemented to constipated rats. The results revealed that SDF increased the serum levels of excitatory gastrointestinal active peptides such as motilin (MTL), gastrin (GAS), and substance P (SP), while concurrently decreasing the levels of inhibitory peptides like somatostatin (SS) and vasoactive intestinal peptide (VIP). SDF restored the ratio of Firmicutes/Bacteriodetes (F/B), upregulated the relative abundance of Lactobacillus and Clostridium, and downregulated the relative abundance of Oscillopira, Ruminococcus, Coprococcus, and Akkermansia; analysis of metabolites revealed that the levels of bile acid, deoxycholic acid, chenodeoxycholic acid, and taurocholic acid were notably elevated after SDF treatment, while the levels of indole-3-lactic acid, putrescine, and L-arginine were significantly decreased. Pathway enrichment analysis found that SDF regulates Taurine and hypotaurine metabolism, Primary bile acid biosynthesis, and Bile secretion. Correlation analysis between gut microbiota and metabolites revealed that Fusibacter and Actinomyces may contribute to alleviating constipation by regulating the level of bile acid in the intestine. SDF intervention increased the mRNA expressions of FABP1 and SLC1A5 in constipated rats. Furthermore, SDF exhibited notable abilities in retaining water and undergoing swelling. The above results showed that SDF helped the intestine lock water and promoted intestinal peristalsis by increasing friction. On the other hand, SDF supplementation increased the relative abundance of Lactobacillus and Clostridium, decreased the relative abundance of Oscillopira, increased the levels of various bile acids such as deoxycholic acid and chenodeoxycholic acid, further regulated intestinal lipid metabolism, up-regulated FABP1 mRNA expression, promoted intestinal cell proliferation, restored intestinal homeostasis, and thus alleviated constipation.

A novel arabinogalactan extracted from Epiphyllum oxypetalum (DC.) Haw improves the immunity and gut microbiota in cyclophosphamide‐induced immunosuppressed mice

AbstractA novel type I arabinogalactan (AG‐I) polysaccharide (EPS) from Epiphyllum oxypetalum (DC.) Haw's flowers is hypothesized to possess immunomodulatory activity. This study investigated EPS's effects on immune functions and its potential mechanism for enhancing intestinal health in immunosuppressed mice. The results showed that supplementing EPS significantly alleviated immune organ damage, increased the thymus index (p &lt; 0.01), and regulated the key immune factors, including the tumor necrosis factor‐alpha (TNF‐α), immunoglobulin A (IgA), and complement 3 (C3) in the liver (p &lt; 0.05). EPS promoted the expression of intestinal immune barrier and chemical barrier proteins such as interferon‐γ (IFN‐γ) and mucin 2 (MUC2) (p &lt; 0.05), effectively repairing intestinal damage. EPS improved the diversity and structure of intestinal microbiota in immunosuppressed mice (p &lt; 0.05) and significantly altered the abundance of intestinal immune‐related microbial taxa, including Lactobacillaceae and Lactobacillus (p &lt; 0.01). Furthermore, EPS supplementation altered intestinal lactic acid metabolism, significantly increasing lactic acid levels by up to 3.4‐fold (p &lt; 0.01), and enhanced the expression of Gpr81, Wnt3a, and β‐catenin proteins at the bottom of the colonic crypts, which may repair the intestinal physical barrier. Overall, EPS represents a novel AG‐I immunomodulatory dietary polysaccharide that enhances immunity and improves gut health.

19F qNMR based pharmacokinetics, metabolism and mass balance studies of SARS-CoV-2-3CL protease inhibitor simnotrelvir (SIM0417) in humans.

Simnotrelvir (SIM0417), an inhibitor of the 3CL protease of SARS-CoV-2, has been identified as a CYP3A sensitive substrate. This study investigated the pharmacokinetics, metabolism, and mass balance of simnotrelvir following a single oral dose of 750 mg in six healthy Chinese male subjects, co-administered with four doses of 100 mg ritonavir. Analysis using 19F qNMR combined with LC-MS/MS showed that the parent drug M0 constituted over 90% of the drug-related components in plasma. Of the administered dose, 55.4% (54.3% of M0) was recovered in urine, while 36.7% (4.57% of M0) was excreted in feces. UPLC/Q-TOF MS was used to identify metabolites in human plasma, urine and feces. Notably, oxidative metabolites catalyzed by CYP3A were scarcely detected in these matrixes. The amide hydrolyzed metabolite M9 and the cyano hydrolyzed metabolite M10 were recognized as the predominant metabolites, with the main excretion being through feces (19.0% and 12.7% of the administered dose, respectively). In vitro experiments indicated that M10 is primarily formed in the duodenum and jejunum, with further metabolism to M9 by microbiota in the large intestine. Overall, the co-administration of simnotrelvir with ritonavir led to predominant metabolism by intestinal enzymes or microbiota, resulting in hydrolyzed metabolites. These findings highlight the critical role of intestinal metabolism in the pharmacokinetics of simnotrelvir and emphasize the need to consider interactions with antibiotics and individual differences of intestinal microbiota.

Effects of Ionizing Radiation on Intestinal Bile Acid Metabolism: Mechanism of the Radioprotective Effect of Glycoursodeoxycholic Acid

Radioactive intestinal injury is a common complication during radiotherapy of tumors. The aim of this study is to observe the effect of ionizing radiation on short-term changes in intestinal bile acids and to investigate the radioprotective effect of bile acids on intestinal cells. A rat model of small intestinal injury was constructed by exposing the abdomen of the rats to daily irradiation at 2 Gy for 4 d in succession. The bile acids were quantified using metabolomics analysis. IEC-6 cells, a small intestinal epithelial cell line, were divided into a dimethyl sulfoxide (DMSO) control group receiving DMSO and 0 Gy irradiation, a glycoursodeoxycholic acid (GUDCA) experimental group receiving GUDCA and 0 Gy irradiation, a DMSO irradiation group receiving DMSO and 10 Gy irradiation, and a GUDCA irradiation group receiving GUDCA and 10 Gy irradiation. Cell viability and cytotoxicity was assessed by CCK-8 assay test. The apoptosis rate of cells was determined by flow cytometry. The colony formation rate and the radiosensitivity of the cells were determined by colony formation assay on solid media. The expression levels of proteins associated with cell death were determined using Western blot. After exposure to irradiation, the small intestine tissues of the rats showed typical radioactive intestinal injury. In addition, various bile acids showed fluctuation before and after irradiation. Among the bile acids, GUDCA increased significantly at 3 d after irradiation, but returned to the pre-irradiation level at 7 d after irradiation. Compared with the control group, after GUDCA treatment at 20 μmol/L for 24 h, the cell viability rate after irradiation was significantly higher than that of the DMSO group (P<0.05); the expression levels of the proteins, including PARP, caspase-3, RIP, and GSDMD, were significantly lower than those in the control group (P<0.05). After GUDCA treatment at 20 μmol/L for 24 h and 48 h, the cell apoptosis rate of the cells after irradiation was lower than that of the DMSO group (P<0.05). Compared with the DMSO control group, the colony formation ability of the GUDCA experimental group was stronger than that of the DMSO group after irradiation at 0, 2, 4, and 6 Gy (P<0.05). D0, or the mean lethal dose, of the GUDCA group was 6.374, while that of the DMSO group was 4.572. Compared with the DMSO control group, the D0 value of the GUDCA treatment group increased, and the sensitization enhancement ratio (SER) was 0.717. After exposing the abdomen of rats to irradiation, the intestinal bile acid metabolism of the rats will change significantly, and GUDCA can produce radioprotective effects on intestinal cells to a certain extent.

Research on the mechanism of buyang huanwu decoction in the amelioration of age-associated memory impairment based on the “co-occurrence network regulation of intestinal microecology-host metabolism-immune function”

Ethnopharmacological relevanceBrain aging can promote neuronal damage, contributing to aging-related diseases like memory dysfunction. Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicine formula known for tonifying qi and activating blood circulation, shows neuroprotective properties. Despite this, the specific mechanism by which BYHWD improves age-associated memory impairment (AAMI) has not been explored in existing literature. Aim of the studyThis study aimed to investigate the mechanism of BYHWD in the improvement of AAMI based on the “co-occurrence network regulation of intestinal microecology-host metabolism-immune function”. Materials and methodsFirstly, D-galactose was performed to induce a rat model of AAMI. Learning and memory deficits was assessed by the Morris water maze test. H&E and Nissl staining were used to observe the pathological changes in neurons in the hippocampus of rats. Meanwhile, the levels of pro-inflammatory cytokines and the activation of antioxidant enzymes in rat serum were measured using ELISA. Finally, an integrated pharmacological approach was applied to explore the potential mechanism of BYHWD in improving AAMI. ResultsOur results indicated that BYHWD significantly mitigated the pathological structure of the hippocampus, reversed the levels of IL-6, TNF-α, GSH, and CAT in the serum, and improved learning and memory in aging rats. Transcriptomics combined with network pharmacology showed that energy metabolism and the inflammatory response were the key biological pathways for BYHWD to ameliorate AAMI. Integrative analysis of the microbiome and metabolomics revealed that BYHWD has the potential to restore the balance of abundance between probiotics and harmful bacteria, and ameliorate the reprogramming of energy metabolism caused by aging in the brain. The co-occurrence network analysis demonstrated that a strong correlation between the treatment of AAMI and the stability of intestinal microecology, host metabolism, and immune network. ConclusionThe findings of this study collectively support the notion that BYHWD has a superior therapeutic effect in an AAMI rat model. The mechanism involves regulating the “intestinal microecology-metabolism-immune function co-occurrence network” system to restore the composition of gut microbiota and metabolites. This further improves the metabolic phenotype of brain tissue and maintains the homeostasis of central nervous system's immunity, leading to an improvement in AAMI. Consequently, this study offers a unique perspective on the prevention and treatment of AAMI. And, BYHWD is also considered to be a promising preclinical treatment for improving AAMI.

The increased tendency for anemia in traditional Chinese medicine deficient body constitution is associated with the gut microbiome.

Constitution is a valuable part of traditional Chinese medicine theory; it is defined as the internal foundation for the occurrence, development, transformation and outcome of diseases, and has its characteristic gut microbiota. Previous study showed that deficiency constitution was related to lower Hb counts. However, no research has examined how alterations in the gut microbiome induced by deficiency constitution may increase the tendency for anemia. We used a multiomics strategy to identify and quantify taxonomies and compounds found under deficient constitution individuals and further explore the possible pathological factors that affect red blood cell indices. ① People with deficient constitution showed lower hemoglobin (Hb), more Firmicutes, less Bacteroidetes, and higher α diversity. ② We identified Escherichia coli, Clostridium bolteae, Ruminococcus gnavus, Streptococcus parasanguinis and Flavonifractor plautii as potential biomarkers of deficient constitution. ③ Slackia piriformis, Clostridium_sp_L2_50 and Bacteroides plebeius were enriched in balanced-constitution individuals, and Parabacteroides goldsteinii was the key bacterial marker of balanced constitution. ④ Flavonifractor plautii may be a protective factor against the tendency for anemia among deficient individuals. ⑤ Ruminococcus gnavus may be the shared microbe base of deficiency constitution-related the tendency for anemia. ⑥ The microorganism abundance of the anaerobic phenotype was lower in deficient constitution group. ⑦ Alterations in the microbiome of deficient-constitution individuals were associated with worse health status and a greater risk of anemia, involving intestinal barrier function, metabolism and immune responses, regulated by short-chain fatty acids and bile acid production. The composition of the gut microbiome was altered in people with deficient constitution, which may explain their poor health status and tendency toward anemia.

Metagenomic and Metabolomic Analyses Reveal the Role of Gut Microbiome-Associated Metabolites in the Muscle Elasticity of the Large Yellow Croaker (Larimichthys crocea).

The large yellow croaker (LYC, Larimichthys crocea) is highly regarded for its delicious taste and unique flavor. The gut microbiota has the ability to affect the host muscle performance and elasticity by regulating nutrient metabolism. The purpose of this study is to establish the relationship between muscle quality and intestinal flora in order to provide reference for the improvement of the muscle elasticity of LYC. In this study, the intestinal contents of high muscle elasticity males (IEHM), females (IEHF), and low muscle elasticity males (IELM) and females (IELF) were collected and subjected to metagenomic and metabolomic analyses. Metagenomic sequencing results showed that the intestinal flora structures of LYCs with different muscle elasticities were significantly different. The abundance of Streptophyta in the IELM (24.63%) and IELF (29.68%) groups was significantly higher than that in the IEHM and IEHF groups. The abundance of Vibrio scophthalmi (66.66%) in the IEHF group was the highest. Based on metabolomic analysis by liquid chromatograph-mass spectrometry, 107 differentially abundant metabolites were identified between the IEHM and IELM groups, and 100 differentially abundant metabolites were identified between the IEHF and IELF groups. Based on these metabolites, a large number of enriched metabolic pathways related to muscle elasticity were identified. Significant differences in the intestinal metabolism between groups with different muscle elasticities were identified. Moreover, the model of the relationship between the intestinal flora and metabolites was constructed, and the molecular mechanism of intestinal flora regulation of the nutrient metabolism was further revealed. The results help to understand the molecular mechanism of different muscle elasticities of LYC and provide an important reference for the study of the mechanism of the effects of LYC intestinal symbiotic bacteria on muscle development, and the development and application of probiotics in LYC.

Capsaicin‐mediated repair of circadian disruption‐induced Intestinal barrier damage via the gut microbiota

AbstractCircadian clock serves as a regulator of gastrointestinal health, and the disruption of circadian rhythm may trigger the dysregulation of the intestinal barrier functions. This study investigated the effectiveness of capsaicin (CAP) in mitigating intestinal barrier dysfunction induced by circadian disruption in male SPF C57BL/6J mice. Our findings indicated that CAP supplementation attenuated abnormal weight gain, alterations in serum lipid levels, and misalignment in hepatic and colonic circadian clock gene expressions in mice caused by constant darkness (CD) treatment. The restoration of the intestinal barrier integrity was also observed through the increase in mucosal thickness and goblet cell numbers. Both the diversity and the circadian rhythm of gut microbiota were improved in CAP‐treated group. Correlation analysis indicated that CAP could modulate the gut microbiota by affecting intestinal barrier function and systemic metabolism in CD‐treated mice. These results highlight the potential of CAP as a functional food component in maintaining the intestinal barrier homeostasis through regulating gut microbiota.

Pangenome analysis of Clostridium scindens : a collection of diverse bile acid and steroid metabolizing commensal gut bacterial strains.

Clostridium scindens is a commensal gut bacterium capable of forming the secondary bile acids deoxycholic acid and lithocholic acid from the primary bile acids cholic acid and chenodeoxycholic acid, respectively, as well as converting glucocorticoids to androgens. Historically, only two strains, C. scindens ATCC 35704 and C. scindens VPI 12708, have been characterized in vitro and in vivo to any significant extent. The formation of secondary bile acids is important in maintaining normal gastrointestinal function, in regulating the structure of the gut microbiome, in the etiology of such diseases such as cancers of the GI tract, and in the prevention of Clostridium difficile infection. We therefore wanted to determine the pangenome of 34 cultured strains of C. scindens and a set of 200 metagenome-assembled genomes (MAGs) to understand the variability among strains. The results indicate that the 34 strains of C. scindens have an open pangenome with 12,720 orthologous gene groups, and a core genome with 1,630 gene families, in addition to 7,051 and 4,039 gene families in the accessory and unique (i.e., strain-exclusive) genomes, respectively. The core genome contains 39% of the proteins with predicted metabolic function, and, in the unique genome, the function of storage and processing of information prevails, with 34% of the proteins being in that category. The pangenome profile including the MAGs also proved to be open. The presence of bile acid inducible ( bai ) and steroid-17,20-desmolase ( des ) genes was identified among groups of strains. The analysis reveals that C. scindens strains are distributed into two clades, indicating the possible onset of C. scindens separation into two species, confirmed by gene content, phylogenomic, and average nucleotide identity (ANI) analyses. This study provides insight into the structure and function of the C. scindens pangenome, offering a genetic foundation of significance for many aspects of research on the intestinal microbiota and bile acid metabolism.

Plasma Biochemistry, Intestinal Health, and Transcriptome Analysis Reveal Why Laying Hens Produce Translucent Eggs.

Producing translucent eggs has been found to reduce the quality and safety of the eggs, as well as the demand from consumers. However, the intestinal function and the molecular mechanism for the production of translucent eggs remain uncertain. A total of 120 eggs from 276-day-old Jining Bairi were divided into two groups based on eggshell translucence: the translucent egg group (group T) and the normal group (group C). Group T exhibited thicker eggshells and a lower egg yolk color. Subsequently, we divided the chickens into translucent and normal groups based on their egg quality. We then assessed the plasma biochemical index, intestinal morphology and structure, enzyme activity, and antioxidant capacity of the hens producing translucent eggs compared to those producing normal eggs. The results showed that the ratio of duodenal villus length to crypt depth, succinate dehydrogenase (SDH) activity, chymotrypsin, total ATPase (T-ATPase), alkaline phosphatase (AKP), and glutathione peroxidase (GSH-Px) activities were decreased in the hens produced translucent eggs (p < 0.05), but malondialdehyde (MDA) content was increased (p < 0.05); jejunal lipase activity, Na+K+-ATPase activity, total antioxidant capacity (T-AOC), and GSH-Px activities were decreased (p < 0.05) in group T; ileal amylase and Ca2+Mg2+-ATPase activities were also decreased (p < 0.05) in group T. In addition, we identified a total of 471 differentially expressed genes (DEGs) in duodenal tissue, with 327 up-regulated genes and 144 down-regulated genes (|log2FC| ≥ 1 and p < 0.05). Enrichment analysis showed that the up-regulated genes, such as GSTT1, GSTO2, and GSTA3, were mostly enriched in metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450, and oxidative phosphorylation pathways. The results of our study indicate that plasma lipid metabolism disorder, decreased intestinal antioxidant capacity, and altered intestinal metabolism capabilities may influence the formation of translucent eggs.

Metabolic disrupting chemicals in the intestine: the need for biologically relevant models: Zebrafish: what can we learn from this small environment-sensitive fish?

Although the concept of endocrine disruptors first appeared almost 30 years ago, the relatively recent involvement of these substances in the etiology of metabolic pathologies (obesity, diabetes, hepatic steatosis, etc.) has given rise to the concept of Metabolic Disrupting Chemicals (MDCs). Organs such as the liver and adipose tissue have been well studied in the context of metabolic disruption by these substances. The intestine, however, has been relatively unexplored despite its close link with these organs. In vivo models are useful for the study of the effects of MDCs in the intestine and, in addition, allow investigations into interactions with the rest of the organism. In the latter respect, the zebrafish is an animal model which is used increasingly for the characterization of endocrine disruptors and its use as a model for assessing effects on the intestine will, no doubt, expand. This review aims to highlight the importance of the intestine in metabolism and present the zebrafish as a relevant alternative model for investigating the effect of pollutants in the intestine by focusing, in particular, on cytochrome P450 3A (CYP3A), one of the major molecular players in endogenous and MDCs metabolism in the gut.

Role of L-carnitine in Cardiovascular Health: Literature Review.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Secondary preventive measures, like anti-platelet medications, B-blockers, and angiotensin-converting enzyme (ACE) inhibitors, have been found to dramatically lower the risk of cardiovascular disease. However, prolonged usage of these drugs has been linked to multiple adverse impacts. Hence, finding more efficient treatments, especially dietary strategies for long-term use in daily life, is advantageous for primary prevention and treatment. L-carnitine, a naturally occurring amino acid derivative normally synthesized in the liver and kidney, is believed to have a considerable influence on cardiovascular health. L-carnitine can enhance both contractile performance and structural integrity of the cardiac muscle by maintaining efficient energy production and reducing oxidative stress. This literature review aims to address several pressing questions regarding the role of L-carnitine in cardiovascular health: what are the physiological functions of L-carnitine, particularly in relation to cardiovascular health; how effective and safe is L-carnitine supplementation in the management of various cardiovascular diseases, primarily ischemic heart disease, heart failure, and peripheral vascular disease; what are the underlying mechanisms through which L-carnitine exerts its cardioprotective effects; what controversies exist in the current research; and finally, what should be the future directions? Through this comprehensive analysis, the review aims to enrich our understanding of L-carnitine's role in cardiovascular health, providing a robust foundation for future academic and clinical endeavors. PubMed, Embase, and Google Scholar have been used to search the following keywords: L-carnitine, cardiovascular health, mitochondrial function, and L-carnitine side effects. Then, using the existing search engine formats, some keyword combinations were used to find the related articles included and every possibility, including using every first keyword combination with another keyword, using every keyword in every place at each given box, etc. Around 308 articles were reviewed using this process, including systemic reviews, meta-analysis studies, randomized controlled trials, and literature review articles. Inthe end, after leaving the pure articles related to the topic as 35 articles, which are attached below with direct citation, the majority of them were very fresh articles, as recent as 2010, and back words, except just one paper related to the impact of L-carnitine post-myocardial infarction, as its data provided us with a positive and promising impact of L-carnitine in this field. L‑carnitine seems to have a pivotal role in cardiovascular health due to its energy metabolism, anti-oxidative stress, and endothelial role. The safety and effectiveness of L-carnitine administration remain an issue for scientific investigation. One of the major concerns is that the intestinal metabolism of L-carnitine generates trimethylamine-N-oxide (TMAO), a compound that has been linked with faster atherosclerosis progression.

Deer oil improves ulcerative colitis induced by DSS in mice by regulating the intestinal microbiota and SCFAs metabolism and modulating NF-κB and Nrf2 signaling pathways.

Deer oil (DO), a byproduct of deer meat processing, possesses high nutritional value. This study aims to evaluate the protective effects of DO on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and to explore its potential mechanisms of action. DO was found to inhibit weight loss and colon shortening in colitis mice, significantly reduce disease activity index scores, and notably enhance the levels of tight junction proteins in colon tissues, thus improving intestinal barrier function. ELISA results indicated that DO markedly alleviated the mice's oxidative stress and inflammatory responses. Western blot analysis further demonstrated that DO significantly inhibited the phosphorylation of NF-κB while up-regulating the expression levels of Nrf2 and HO-1 proteins. Additionally, DO increased the abundance of beneficial bacteria such as Odoribacter, Blautia, and Muribaculum, reduced the abundance of harmful bacteria such as Bacteroides, Helicobacter, and Escherichia-Shigella, and promoted the production of short-chain fatty acids. Our study provides the first evidence that DO can effectively improve DSS-induced UC in mice. The underlying mechanisms may involve maintaining intestinal barrier function, inhibiting inflammation, alleviating oxidative stress, and modulation of gut microbiota. These findings offer valuable insights for developing DO as an adjunct treatment for UC and as a functional food. © 2024 Society of Chemical Industry.

Structural characteristics and intestinal flora metabolism mediated immunoregulatory effects of Lactarius deliciosus polysaccharide

Lactarius deliciosus, a widely appreciated mushroom with delightful tastes and texture, has exhibited immunomodulatory activity in vitro, while the effects on intestinal flora metabolisms in vivo are ambiguous. In this study, a L. deliciosus polysaccharide (LDP) was extracted and purified, and the structural characteristics were evaluated, as well as the immunological enhancement on tumor-bearing mice through regulating intestinal flora metabolisms. Results showed that LDP was a heteropolysaccharide (average molecular weight of 1.44 × 107 Da) with a backbone of α-(1 → 6)-Manp and branches of α-(1 → 6)-Galp, α-(1 → 3)-Fucp, α-(1 → 6)-Glcp, α-(1 → 4)-Glcp. Animal experiments indicated that LDP could significantly protect immune organs of tumor-beraing mice and suppress solid tumors growth with inhibitory rate of 51.61 % (high-dose, 100 mg/kg), and improve the intestinal lactobacillus contents, promote adenine mediated zeatin biosynthesis, then competitively antagonize A2A receptor and enhance the activities of CD4+ T cells and CD8+ T cells, finally effectively facilitate the apoptosis and elimination of tumor cells. These results would provide powerful data supports for the further antitumor mechanisms development and practical applications of L. deliciosus polysaccharide in food and drug industries.

Protective effect of walnut active peptide against dextran sulfate sodium-induced colitis in mice based on untargeted metabolomics

Inflammatory bowel disease (IBD) is a chronic condition characterized by inflammation of the digestive tract, whose exact cause remains unknown, and its prevalence is on the rise. This study investigated the effects of a walnut-derived peptide LPLLR (LP-5) on intestinal inflammation and metabolism in IBD mice. Metabolomics revealed that LP-5 regulated the levels of metabolites, such as thalsimidine, fumagillin, and geniposide, and LP-5 could regulate several signaling pathways, such as protein digestion and absorption, aminoacyl-tRNA biosynthesis, and ABC transporters. Additionally, LP-5 alleviated dextran sulfate sodium (DSS)-induced colitis by modulating autophagy and inflammasome pathways. Western blotting demonstrated that LP-5 reduced the expressions of NLRP3, Caspase-1, ASC and IL-1β, and increased the expressions of Beclin-1 and LC3-II/LC3-I, corresponding to activation of the AMPK/mTOR/ULK1 pathway. These findings suggested that LP-5 activated autophagy in vivo to suppress inflammation and modulate metabolic substances, highlighting potential implications for gut health and the development of functional foods containing LP-5.