Intestinal Metabolism Research Articles

Structural characterization of an acid-extracted polysaccharide from Suillus luteus and the regulatory effects on intestinal flora metabolism in tumor-bearing mice

Suillus luteus is an excellent edible fungus that has been applied in soil remediation and environmental pollution control, while the development of bioactive polysaccharide component including structural performance and intestinal flora regulation is still insufficient. In this study, a S. luteus acid-extracted polysaccharide (SLAP) was prepared under room temperature, then the structural characteristics and regulatory effects on gut microbiota metabolism in tumor-bearing mice were investigated. Results showed that SLAP was a kind of gulcomannan (average molecular weight of 1.76 × 107 Da) comprised of Xyl, Man, Glc, Gal (molar ratio of 0.19:1.00:0.72:0.53), which took β-(1 → 4)-Manp and β-(1 → 4)-Glcp as the backbone with β-(1 → 6)-Glcp and α-(1 → 6)-Galp as branches. The animal experiment results demonstrated that SLAP could effectively enhance the immunoregulatory activities of CD4+ and CD8+ T cells in tumor-bearing mice via improving intestinal lactobacillaceae contents and promoting primary bile acids biosynthesis, finally leading to the suppression of solid tumors growth with an inhibitory rate of 61.14 % (100 mg/kg·d). These results would provide certain data support and research basis for further applications of SLAP as an immunomodulatory adjuvant in food and medicine fields.

Preparation Process Optimization of Glycolipids from Dendrobium officinale and the Difference in Antioxidant Effects Compared with Ascorbic Acid

Background:Dendrobium officinale glycolipids (DOG), often left as residues after hot water extraction for polysaccharide production, are often discarded. Methods: This study investigates the optimal extraction of DOG using response surface methodology, focusing on liquid–solid ratios, ethanol concentrations, extraction temperatures, and extraction times, while preliminarily analyzing DOG’s structural properties. Additionally, the differences in antioxidant effects between DOG and ascorbic acid based on intestinal flora metabolism were further evaluated. Results: The optimal parameters for DOG extraction were determined as follows: liquid–solid ratio of 20 mL/g, ethanol concentration of 70%, extraction temperature of 70 °C, and extraction time of 2.5 h, yielding 2.64 ± 0.18%. In addition, DOG was identified as a diglyceride, mainly composed of glucose, mannose, linoleic acid, 9,12,15-octadecatrienoic acid, and presented certain direct free radicals scavenging effects. In animal experiments, unlike the direct free scavenging effects of ascorbic acid, DOG increased intestinal Bacteroides acidifaciens abundance in mice, up-regulated piceatannol expression, and down-regulated 1-naphthol expression, which contributed to antioxidant effects by enhancing the activities of SOD and GSH-Px while reducing MDA content. Conclusions: DOG was a diglyceride isolated from D. officinale residues after hot water extraction, and presented strong antioxidant effects by regulating intestinal flora metabolism. These findings could promote the efficient utilization of D. officinale and support further development of DOG in functional food applications.

Angelica sinensis Polysaccharide Alleviates Staphylococcus aureus-Induced Mastitis by Regulating The Intestinal Flora and Gut Metabolites.

The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae_NK4A136 while reducing Erysipelatoclostridium. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.

Bibliometric Analysis of Traditional Chinese Medicine in the Treatment of Asthma from 2005 to 2024

Asthma is a complex chronic respiratory disease that affects most people worldwide and imposes a heavy economic and health burden. Traditional Chinese medicine (TCM) is one of the common treatments for asthma; however, there is a lack of bibliometric analysis data on the relationship between bronchial asthma and traditional Chinese medicine. This study analyzes and visualizes current research status and future trends. Relevant English publications on traditional Chinese medicine treatment for bronchial asthma were collected from the Web of Science core collection, and bibliometric analysis was conducted using software like Histcite. A total of 406 articles meeting the criteria were included after manual screening. China (including Taiwan) emerged as the leading contributor, with the Beijing University of Chinese Medicine being the institution with the highest number of publications. 'Journal of Ethnopharmacology' was a significant publication in this domain. The most frequently occurring keyword on the main display platform was 'airway inflammation.' Future research hotspots are expected to focus on intestinal flora and metabolism. This research offers a fresh perspective for understanding developments in this field.

Building Confidence in Physiologically Based Pharmacokinetic Modeling of CYP3A Induction Mediated by Rifampin: An Industry Perspective.

Physiologically-based pharmacokinetic (PBPK) modeling offers a viable approach to predict induction drug-drug interactions (DDIs) with the potential to streamline or reduce clinical trial burden if predictions can be made with sufficient confidence. In the current work, the ability to predict the effect of rifampin, a well-characterized strong CYP3A4 inducer, on 20 CYP3A probes with publicly available PBPK models (often developed using a workflow with optimization following a strong inhibitor DDI study to gain confidence in fraction metabolized by CYP3A4, fm,CYP3A4, and fraction available after intestinal metabolism, Fg), was assessed. Substrates with a range of fm,CYP3A4 (0.086-1.0), Fg (0.11-1.0) and hepatic availability (0.09-0.96) were included. Predictions were most often accurate for compounds that are not P-gp substrates or that are P-gp substrates but that have high permeability. Case studies for three challenging DDI predictions (i.e., for eliglustat, tofacitinib, and ribociclib) are presented. Along with parameter sensitivity analysis to understand key parameters impacting DDI simulations, alternative model structures should be considered, for example, a mechanistic absorption model instead of a first-order absorption model might be more appropriate for a P-gp substrate with low permeability. Any mechanisms pertinent to the CYP3A substrate that rifampin might impact (e.g., induction of other enzymes or P-gp) should be considered for inclusion in the model. PBPK modeling was shown to be an effective tool to predict induction DDIs with rifampin for CYP3A substrates with limited mechanistic complications, increasing confidence in the rifampin model. While this analysis focused on rifampin, the learnings may apply to other inducers.

The effect of anti‐imbalance on glycolipid metabolic homeostasis via the liver–gut axis intervened by 3′‐sialyllactose in obese mice

AbstractSialic acid could ameliorate disorders associated with glycolipid metabolism. 3′‐Sialyllactose (3′‐SL), a type of oligosaccharide, contains sialic acid. We examined the effects of 3′‐SL on glycolipid metabolism in obese mice with high fat diet and explore the underlying mechanisms. A total of 160 male C57BL/6J mice were fed with high‐fat diet for 8 weeks to construct obese mice model. Sixty successfully constructed obese mice were randomly divided three 3′‐SL dosage‐dependent groups, one free sialic acid N‐acetylneuraminic acid (Neu5Ac) group, and one blank control group. Each group of obese mice (n = 12) was continuously supplemented by 3′‐SL or Neu5Ac for 10 weeks. Ten‐week 3′‐SL supplementation and Neu5Ac supplementation both yielded remarkedly lower body weight, reduced fat content, increased energy expenditure and active daily exercises with improved glycolipid biomarkers, and attenuated proinflammation. 3′‐SL increased the colonic abundances of Akkermansia, Lactobacillus, and Solibacillus and reduced those of Enterobacter and Enterococcus. Changes were also observed in colonic and liver transcript and metabolites, which were mainly enriched in glycolipid metabolism, ameliorated immune function, and mitigated inflammatory signals, autophagy, bile acid metabolism, and insulin resistance. Akkermansia and Solibacillus were significantly associated with changes in colonic metabolites and transcriptome genes. The liver bile component and glucose metabolites were significantly correlated with transcriptional gene expression in the aforementioned differential pathways. Therefore, 3′‐SL can enhance the gut microbiota, regulate intestinal immunity and bile acid metabolism, reduce liver oxidative stress and autophagy processes, alleviate chronic inflammation levels, and improve islet function and lower blood sugar levels by acting through the gut–liver axis.

8780 The Role of Nuclear Receptor Corepressors 1 and 2 on Intestinal Carbohydrate Transport in Mice

Abstract Disclosure: M.J. Ritter: None. I. Amano: None. A.H. van der Spek: None. H.E. Daniel: None. A.N. Hollenberg: None. The nuclear receptor corepressors NCoR1 and NCoR2 are two critical regulators of metabolism that are required for maintaining metabolic homeostasis. Both NCoR1 and NCoR2 (also known as the silencing mediator of retinoic acid and thyroid hormone receptors; SMRT) recruit histone deacetylase 3 (HDAC3) to their deacetylase domain (DAD) to repress nuclear receptor (NR) target gene expression. Interruption of the DAD of NCoR1 in mice leads to lower body weight, decreased whole-body fat mass, insulin sensitization with altered oscillatory patterns of key metabolic genes (1). On the other hand, total body knock-out (KO) of SMRT leads to weight gain, insulin resistance, and hepatic steatosis with an increase in hepatic lipogenesis (2). Previously, we showed that the KO of NCoR1 and SMRT in tandem from adult mice led rapidly to weight loss, hypoglycemia, hypothermia and was lethal. Reductions in intestinal carbohydrate transporters were seen, including sodium-glucose linked transporter-1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5) (3). Thus, we hypothesized that NCoR1 and SMRT play unique roles in regulating intestinal carbohydrate metabolism, in turn controlling metabolic parameters including body mass and glucose levels. We then generated a novel model to enable KO of NCoR1 and SMRT throughout intestinal epithelial cells (IECs) in adult mice using a tamoxifen inducible cre under control of the villin 1 promoter. Mice were injected with tamoxifen and body weight and glucose were monitored daily. This was followed by both oral and intraperitoneal glucose tolerance testing (GTT) and metabolic phenotyping. Preliminary data showed that NCoR1 and SMRT KO leads to sustained weight loss and hypoglycemia with 50% survivability. Metabolic phenotyping confirmed reduction in body mass without concomitant reduction in food intake. Oral GTT showed a blunted peak in response to glucose gavage compared to intraperitoneal administration. Gene expression analysis showed reduction in SGLT1, GLUT2, and GLUT5 in addition to changes in metabolic pathways associated with fatty acid metabolism. Here, we show that NCoR1 and SMRT are critical regulators of body mass and glucose in part via their actions on carbohydrate transporters in the intestine. With the global burden of metabolic diseases, including obesity and diabetes, ever-rising, NCoR1 and SMRT represent an overlooked but important area of study to better our understanding of disease processes and identify new targets for treatment. We next aim to determine the functional mechanism by which weight loss and hypoglycemia develop in addition to identifying molecular targets and pathways regulated by NCoR1 and SMRT in IECs.

Association of Serum Bile Acid Profile with Diet and Physical Activity Habits in Japanese Middle-Aged Men.

Circulating bile acid (BA) profiles change with lifestyle and are closely related to intestinal BA metabolisms such as deconjugation and conversion to secondary BAs. The composition of BA in the blood is involved in systemic nutrient metabolism and intestinal health. Herein, we explored the associations of lifestyle and physical fitness with the circulating BA profile of middle-aged men. Data of 147 male participants (aged 50-64 years; BMI < 26 kg/m2; no medication for diabetes or dyslipidemia) from the Japan Multi-Institutional Collaborative Cohort study were analyzed. Serum concentrations of 15 types of BAs were examined for associations with variables on dietary habits, physical-activity habits, and physical fitness. Green tea intake was positively associated with the deconjugation ratio of total BAs (p = 0.028) and negatively associated with secondary BA levels (free deoxycholic acid [DCA] (p = 0.078), glyco-DCA (p = 0.048), and tauro-DCA (p = 0.037)). In contrast, physical activity was negatively associated with the deconjugation ratio (p = 0.029) and secondary BA levels (free DCA (p = 0.098), and free lithocholic acid (p = 0.009)). Grip strength was also negatively associated with secondary BA levels (tauro-DCA (p = 0.041)) but was not associated with the deconjugation ratio. Energy and fat intake and skeletal muscle mass were not associated with the deconjugation ratio or secondary BA levels. The study findings suggest that lifestyle-associated changes in serum deconjugated and secondary BAs indicate improvements in nutrient metabolism and the intestinal environment.

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.

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.

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.

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.