內容: The development of rodent models that accurately reflect the pathogenesis of alcoholic liver disease (ALD) in humans is crucial for evaluating the nutritional intervention of food bioactive ingredients in ALD. Although various models have been employed to establish ALD models over the past few decades, most successful cases are associated with high mortality rates, operational difficulties, and incompatibility formation mechanism compared to human ALD. However, the ALD models established by oral administration that simulate human drinking behavior often fail to induce significant liver damage. Therefore, it is imperative to explore simple and effective modes of oral administration for establishing ALD models consistent with the pathophysiological process of human ALD. Herein, we summarized the pathogenesis of ALD and discussed several issues related to construct ALD models with rodents (mainly mice and rats) by oral administration, including animal selection, animal feeding, alcohol intervention, and evaluation criteria. The purpose of this review is to provide a standardized and efficient formula for ALD modeling, so as to facilitate efficacy evaluation and mechanism analysis of food bioactive ingredients in ALD.

內容: Lactic acid bacteria and the fermentation environment interact to form an intertwined system. Lactic acid bacteria are constantly evolving to adapt to different fermentation environments, causing changes in their physiological processes. To achieve a targeted improvement of their adaptability to various environments, a detail analysis of their evolutionary physiological processes is required. While several studies have been carried out in the past by using single-omics techniques to investigate their response to environmental stress, most researchers are now using a multi-omics approach to explore more detail in the biological regulatory networks and molecular mechanisms of lactic acid bacteria in response to environmental stress, thereby overcoming the limitations of single- omics analysis. In this review, we describe the various single-omics approaches that have been used to study environmental stress in lactic acid bacteria, present the advantages of various multi-omics combined analysis approaches, and discuss the potential and practicality of applying emerging single-cell transcriptomics and single-cell metabolomics techniques to the molecular mechanism study of microbes response to environmental stress. Multi-omics approaches enable the accurate identification of complex microbial physiological processes in different environments, allow people to comprehensively reveal the molecular mechanisms of microbes response to stress from different perspectives. Single-cell omics techniques, analyze the targeted regulation of microbial functions in a multi-dimensional space, provides a new perspective on understanding microbes responses environment stress.

內容: Chlorogenic acid (CA) is a natural plant-derived polyphenol compound that is widely present in beverages (coffee and tea), fruits (blueberry, apple, and mulberry), and medicinal plants (Lonicera japonica, Eucommia ulmoides, and Cichorium intybus). In recent years, CA has attracted extensive attention due to its various health benefits, such as anti-inflammatory, immunomodulatory, anti-obesity, anti-diabetes mellitus, and neuroprotection activities. Interestingly, the low bioavailability of CA corresponds to high bioactivity, which raises a key scientifi c question of how low bioavailability CA can achieve high biological activity. In this review, we highlight the gut microbiota as a key target for connecting the two by summarizing a large amount of evidence. Specifi cally, the composition and abundance of gut microbiota, its metabolites, intestinal immunity, barrier function and so on were all changed under different pathological conditions such as infl ammatory bowel disease, liver disease, kidney disease, cardiovascular disease, diabetes mellitus, obesity, etc. Conversely, these changes could be reversed by CA. In a word, CA could achieve pharmacological activity as well as health-protective effects by modulating intestinal immune and barrier function, gut microbiota composition, gut microbiota metabolites, and signaling pathways. This review provides new targets for the prevention and treatment of diseases by CA. Meanwhile, regulating the composition of the gut microbiota through natural products may be a potential strategy to achieve health protection.

內容: Antibiotic exposure has adverse effects on intestinal immunity, metabolism, and gut microbiota (GM) composition, particularly by disturbing GM composition without short-term recovery. Capsaicin, a dietary irritant, is generally avoided during antibiotic therapy, but its mechanism remains unclear. To explore the effects of capsaicin on intestinal health during antibiotic administration, we conducted experiments in specifi c pathogen free (SPF) and germ-free (GF) mice and correlation analyses using 16S rRNA sequencing and nontargeted metabolomics to explore the protective role of the intestinal biological barrier. The results showed that additional supplementation of capsaicin under antibiotic exposure did not cause serious damage to the intestine, but had potential adverse effects on the structure, function, and metabolites of GM, including increasing the abundance of opportunistic pathogens (Mucispirillum and Aeromonas), enriching metabolic pathways (arachidonic acid metabolism and lipopolysaccharide biosynthesis), and metabolites associated with colon infl ammation (N-acetylhistamine). In the absence of GM barrier, the benefi cial function of capsaicin on the intestine was weakened and even induced adverse effects, suggesting that GM may have a certain mediating mechanism in the physiological function of capsaicin.

內容: The study of ligand-receptor interactions is of great significance in food flavor perception. In this study, a computer simulation method was used to investigate the mechanism of interaction between umami peptides and T1R1/T1R3-Venus-flytrap domain (VFT) receptor. The binding site, conformational changes, and binding free energy between umami peptides and T1R1/T1R3-VFT were analyzed through molecular modeling, molecular docking, and molecular dynamics simulations. The receptor model constructed using AlphaFold2 has the best rationality. The molecular docking results showed that umami peptides primarily bound to T1R1- VFT through hydrogen bonding, with key binding residues such as Thr149, Arg151, and Asp108. The binding of umami peptides led to a more stable complex system, and the positively charged amino acids contributed positively to the overall binding free energy. This study provides theoretical support for the development of a better understanding of the interaction between umami substances and the umami receptor.

內容: Identification of natural substances with antioxidant properties is ongoing research for addressing issues related to oxidative stress especially attributed to environmental effects. Our previous study demonstrated that Lateolabrax japonicus peptides (LPH), rich in Glu, Gly, and hydrophobic amino acids, exhibited remarkable antioxidant activity in vitro, with though its action mechanism yet to be revealed. Therefore, to assess the in vivo antioxidative properties of LPH, we employed H2O2 to generate oxidative stress in Drosophila melanogaster model. Results indicated that LPH significantly prolonged the lifespan of Drosophila subjected to oxidative stress mostly mediated via LPH’s enhancement of the antioxidant defense system and intestinal functions. Antioxidant effects were manifested by a decrease in malondialdehyde (MDA) levels, elevated superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, decreased levels of reactive oxygen species (ROS) in intestinal epithelial cells, and the preservation of intestinal length. LPH effectively controlled the excessive proliferation and differentiation of oxidative stress-induced Drosophila intestinal stem cells. At the gene level, LPH upregulated the expression of antioxidant-related Nrf2 genes while concurrently downregulated mTOR expression level. Furthermore, high-throughput 16S rDNA sequencing revealed that the addition of LPH significantly influenced the diversity and abundance of the intestinal microbiota in H2O2-induced Drosophila. These findings provide a deeper understanding of the antioxidative mechanism of LPH, suggesting its potential applications in food industry and to be assessed using other in vivo oxidative stress models.

內容: Chlorogenic acid (CGA), as a polyphenol abundant in daily diet, exerted various intestinal functions. However, the material basis of its intestinal bioactivities was still unclear. Our study investigated the gastrointestinal distribution of CGA using ultra high performance liquid chromatography-tandem mass spectrum (UPLC-MS/MS) and explored the main drivers leading to different metabolic fates of the metabolites. After oral administration of 50 mg/kg bw CGA to mice, CGA and sulfated metabolites were mainly determined in small intestine. Protocatechuic acid, catechol, and 3-hydroxyphenylpropionic acid were found in copious amounts in large intestine and feces. Besides, caffeic acid existed in the entire intestine and feces. In the in vitro mice/human fecal fermentation of CGA, the production of metabolites was consistent with that in the colon, indicating that microorganisms might lead to the difference in the gastrointestinal distribution of CGA metabolites. Moreover, CGA, 3-hydroxyphenylpropionic acid, protocatechuic acid, catechol, and caffeic acid reduced proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)) and increased mucin (Muc2) and tight junction (occludin) mRNA in LPS-induced Caco-2/HT-29 MTX co-culture cells. In conclusion, the biotransformation of CGA in different gastrointestinal tracts varied significantly, and its metabolites could partially support its intestinal bioactivities.

內容: In study, we investigated the effect of treatment with combination of walnut peptides with molecular weight < 3 kDa and ginsenoside Rg1 (< 3 kDa + Rg1) on scopolamine-induced cognitive impairment in mice and the mechanism of brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrKB)/cAMP response element-binding protein (CREB) signaling pathway in PC12 cells. In behavioral experiments, < 3 kDa + Rg1 treatment improved the memorizing ability of mice. Treatment with < 3 kDa + Rg1 significantly regulated the function of neurotransmitters and effectively improved the morphology of the neurons determined by hematoxylin and eosin (H&E), Nissl, and Golgi staining. Additionally, immunohistochemistry showed that the < 3 kDa + Rg1 treatment significantly decreased acetylcholinesterase (AChE) activity and increased choline acetyl transferase (ChAT) content in the hippocampus. The treatment upregulated vesicular acetylcholine transporter (VAChT), activated the BDNF/TrKB/CREB signaling pathway, improved the remodeling of dendritic spines, and enhanced cholinergic functions. In the scopolamine-induced PC12 cells, combination treatment increased thioredoxin-1 (Trx-1) expression after administering TrKB and activated signaling pathway. The results showed combination of < 3 kDa + Rg1 activated the BDNF/TrKB/CREB signaling pathway by regulating function of neurotransmitters and enhanced cholinergic function to decrease cognitive impairment.

內容: Immunosuppressants currently approved for the treatment of autoimmune diseases and organ transplant rejection present diverse adverse effects that impair the life quality of patients. Therefore, the development of novel immunomodulators with high efficiency and low toxicity is essential. Ellagic acid (EA), a natural polyphenol compound widely distributed in berries, is metabolically transformed by gut microbiome to exert systemic health benefits. Here, we identified that intraperitoneal administration of EA with no cytotoxicity, beyond its wellknown oral metabolic fate, effectively decreased clinical severity and central nervous system (CNS) inflammation/demyelination in experimental autoimmune encephalomyelitis, a mouse model of an autoimmune disease multiple sclerosis. Interestingly, intraperitoneal EA administration at incredibly low doses (0.1 mg/(kg·day)) is dose-sparing with fingolimod (FTY720), the first FDA-approved oral drug for MS. In addition, intraperitoneal EA also ameliorated the brain damage in a neuromyelitis optica (NMO) model, and significantly prevented the immune rejection of allograft skin graft. Evidence from pharmacological studies combined with RNA-seq indicate that prototype EA functions by a mechanism that involves direct inhibition of casein kinase II (CKII) to suppress the expression of IL-17 and promote the expression of Cpt1a to regulate T helper cell 17 differentiation. In conclusion, our study demonstrates that the prototype EA entering the blood circulation acts as a novel therapeutic immunomodulator for the treatment of autoimmune diseases and transplant rejection through the CKII-mediated Janus kinase/signal transducer and activator of transcription 3 Cpt1a signaling pathway.

內容: Selenium nanoparticles (SeNPs) are increasingly recognized for their exceptional antibacterial properties. This study aimed to develop a green, safe, and efficient method for the biosynthesis of SeNPs using the fungus Eurotium cristatum, a novel approach in SeNP synthesis. The process yielded (36.40 ± 4.22) mg of SeNPs per liter of 1.2 mmol/L sodium selenite supplementation. These SeNPs exhibited an average diameter of 231.7 nm and a negative charge, and they remained stable when stored at 4 ℃ . Ultraviolet and visible spectrophotometry revealed a maximum absorption peak at 212 nm, suggesting effective nanoparticle formation. Fourier transform infrared spectrometry indicated that proteins and carbohydrates in the mycelium contributed to the SeNP synthesis. Concentrations of SeNPs below 50 μg Se/mL did not exhibit cytotoxic effects on the growth and proliferation of human hepatocyte L-02 cells. The minimum inhibitory concentration of SeNPs was found to be 2 mg/mL against both methicillin-resistant Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). The SeNPs compromised the cellular integrity of test strains, causing leakage of intracellular contents and disruption of the oxidative stress system, leading to irreversible damage. Our results demonstrate the potential of SeNPs biosynthesized by E. cristatum to act as effective antibacterial agents, signifying a novel and promising approach to developing natural antimicrobial solutions.