Targeted discovery of gut microbiome-remodeling compounds for the treatment of systemic inflammatory response syndrome.

Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.

Enhancing the antioxidant capacity and quality attributes of fermented goat milk through the synergistic action of Limosilactobacillus fermentum WXZ 2-1 with a starter culture.

This study evaluated 75 strains of lactic acid bacteria (LAB) isolated from traditional dairy products in western China for their probiotic properties. Among them, Limosilactobacillus fermentum WXZ 2-1, Lactiplantibacillus plantarum TXZ 2-35, Companilactobacillus crustorum QHS 9, and Companilactobacillus crustorum QHS 10 demonstrated potential probiotic characteristics. The antioxidant capacity of these 4 strains was assessed, revealing that L. fermentum WXZ 2-1 exhibited the highest antioxidant capacity. Furthermore, when cocultured with Streptococcus salivarius ssp. thermophilus and Lactobacillus delbrueckii ssp. bulgaricus, L. fermentum WXZ 2-1 demonstrated a synergistic effect in growth medium and goat milk. To explore its effect on goat milk fermentation, different amounts of L. fermentum WXZ 2-1 were added to goat milk, and its physicochemical properties, antioxidant activity, flavor substances, and metabolomics were analyzed. The study found that the incorporation of L. fermentum WXZ 2-1 in goat milk fermentation significantly improved the texture characteristics, antioxidant capacity, and flavor of fermented goat milk. These findings highlight the potential of L. fermentum WXZ 2-1 as a valuable probiotic strain for enhancing the functionality and desirability of fermented goat milk, contributing to the development of novel functional foods with improved health benefits and enhanced quality attributes.

Roles of intestinal Parabacteroides in human health and diseases.

The stability of gut microbiota is essential for the host's health. Parabacteroides spp., core members of the human gut microbiota, have an average abundance of 1.27% in humans of 12 populations. Parabacteroides have recently been reported to have a close relationship with host health (e.g. metabolic syndrome, inflammatory bowel disease and obesity). Parabacteroides have the physiological characteristics of carbohydrate metabolism and secreting short chain fatty acids. However, antimicrobial resistance of Parabacteroides to antibiotics (such as clindamycin, moxifloxacin and cefoxitin) should not be ignored. In this review, we primarily focus on Parabacteroides distasonis, Parabacteroides goldsteinii, Parabacteroides johnsonii and Parabacteroides merdae and discuss their relationships with host disease, diet and the prevention or induction of diseases. Pa. distasonis and Pa. goldsteinii may be viewed as potential next generation probiotic candidates due to their protective effects on inflammation and obesity in mice. We also discuss the potential therapeutic application of Parabacteroides spp. in maintaining host-intestine homeostasis.

Full components conversion of lignocellulose via a closed-circuit biorefinery process on a pilot scale.

This study developed a closed-circuit biorefinery process for full conversion of lignocellulose into ethanol, biogas and organic fertilizer with zero waste on a pilot scale. In the process, subcritical water pretreatment could effectively break the structure of wheat straw (WS), and ethanol was obtained from pretreated wheat straw (PWS) using two batches of simultaneous saccharification and fermentation (SSF). The pretreatment and ethanol fermentation wastes were reused for biogas and organic fertilizer production by anaerobic digestion (AD), whereas the pretreatment and ethanol conversion efficiency were reduced when supernatant after AD was recovered for next batch pretreatment. The yields of ethanol (0.08-0.09 g/g), biogas (0.05-0.10 L/g) and organic fertilizer (0.55-0.79 g/g) were demonstrated through mass balance. Furthermore, the hidden problems were exposed on pilot-scale conversion process, and several strategies were provided for optimizing the biorefinery process in the future.

Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.

Mechanistic target of rapamycin complex 1 (mTORC1) is a multi-protein complex widely found in eukaryotes. It serves as a central signaling node to coordinate cell growth and metabolism by sensing diverse extracellular and intracellular inputs, including amino acid-, growth factor-, glucose-, and nucleotide-related signals. It is well documented that mTORC1 is recruited to the lysosomal surface, where it is activated and, accordingly, modulates downstream effectors involved in regulating protein, lipid, and glucose metabolism. mTORC1 is thus the central node for coordinating the storage and mobilization of nutrients and energy across various tissues. However, emerging evidence indicated that the overactivation of mTORC1 induced by nutritional disorders leads to the occurrence of a variety of metabolic diseases, including obesity and type 2 diabetes, as well as cancer, neurodegenerative disorders, and aging. That the mTORC1 pathway plays a crucial role in regulating the occurrence of metabolic diseases renders it a prime target for the development of effective therapeutic strategies. Here, we focus on recent advances in our understanding of the regulatory mechanisms underlying how mTORC1 integrates metabolic inputs as well as the role of mTORC1 in the regulation of nutritional and metabolic diseases.

Antibiofilm Effects of Bacteriocin BMP32r on Listeria monocytogenes.

Listeria monocytogenes is a well-known foodborne pathogen that usually lives as biofilm to cope with unfavorable surroundings. Bacteriocins have been reported as antimicrobial compounds, and their bactericidal actions have been extensively studied, but their antibiofilm actions have rarely been studied. Previous study indicated that bacteriocin BMP32r has a broad-spectrum antibacterial activity. In this study, the efficacy of BMP32r against the planktonic bacteria, inhibition of forming biofilm, destruction of mature biofilm, and kill persisters of L. monocytogenes ATCC 15,313 was determined. BMP32r exhibited the bactericidal effect on L. monocytogenes planktonic bacteria. Crystal violet staining showed that sub-minimum inhibitory concentrations (SICs) of BMP32r (1/32 × MIC and 1/16 × MIC) significantly (p < 0.001) inhibit the biofilm formation. In addition, the results of CCK-8, plate count, ruthenium red staining, scanning electron microscopy, and real-time quantitative PCR assay showed that SICs of BMP32r reduced cell adhesion, exopolysaccharide production, quorum sensing, and virulence genes expression in biofilm formation. Moreover, higher concentrations of BMP32r (2 × MIC and 4 × MIC) disrupt the mature biofilm by killing the bacteria in the biofilm and kill L. monocytogenes persisters bacteria effectively. Therefore, BMP32r has promising potential as an antibiofilm agent to combat L. monocytogenes.

Systematic evaluation of a series of pectic polysaccharides extracted from apple pomace by regulation of subcritical water conditions.

To investigate the influences of different subcritical water conditions on apple pomace pectic polysaccharides (APP) extraction, 20 samples were successfully prepared and systematically analyzed. At low temperature region (100-120 °C), extraction effect was predominant and extracted APP was high molecular weight, esterification degree and galacturonic acid content as well as light color. At middle temperature region (140 °C), the balance of extraction and degradation effects was reached and led to the highest APP yield (14.89%). At high temperature region (160-180 °C), degradation effect was predominant and led to serious degradation of APP and more extraction of co-extracts, which endowed the APP with low viscosity and good antioxidant activities in vitro. Overall, the relationship between different subcritical water conditions and APP properties are preliminarily illuminated, which not only provides a promising way for directed extraction of specific APP, but also promotes the potential application of subcritical water to commercial pectin.

Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via reshaping intestinal microenvironment and alleviating inflammatory response.

PURPOSE: Gut microbiota has been reported to contribute to either prevent or promote colorectal cancer (CRC), and treatment with probiotics might be a promising intervention method. The present study aimed to evaluate the potential anti-CRC effects of Lactobacillus coryniformis MXJ32 on a colitis-associated (CA)-CRC mouse model. METHODS: The CA-CRC mouse model was induced by a single intraperitoneal injection of 10 mg/kg azoxymethane and followed by three 7-day cycles of 2% dextran sulfate sodium in drinking water with a 14-day recovery period. Mice were supplemented with L. coryniformis MXJ32 by oral gavage (1 × 109 CFU/day/mouse). The CA-CRC attenuating effects of this probiotic were assessed via intestinal barrier integrity, inflammation, and gut microenvironment. RESULTS: Treatment with L. coryniformis MXJ32 could significantly inhibit the total number of tumors and the average tumor diameter. This probiotic administration prevented the damage of intestinal barrier function by enhancing the expression of tight junction proteins (Occludin, Claudin-1, and ZO-1) and recovering the loss of goblet cells. Moreover, L. coryniformis MXJ32 alleviated intestinal inflammation via down-regulating the expression of inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-γ, and IL-17a) and chemokines (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Ccl7). In addition, L. coryniformis MXJ32 supplementation increased the abundance of some beneficial bacteria (such as SCFAs-producing bacteria, Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and decreased the abundance of some harmful bacteria (such as pro-inflammatory bacteria, Desulfovibrio and Helicobacter), which in turn attenuated the overexpression of inflammation. CONCLUSION: Lactobacillus coryniformis MXJ32 could effectively ameliorate CA-CRC via regulating intestinal microenvironment, alleviating inflammation, and intestinal barrier damage, which further suggested that L. coryniformis MXJ32 could be considered as a functional food ingredient for the alleviation of CA-CRC.

T-2 Toxin Induces Ferroptosis by Increasing Lipid Reactive Oxygen Species (ROS) and Downregulating Solute Carrier Family 7 Member 11 (SLC7A11).

T-2 toxin is a trichothecene mycotoxin commonly found in animal feed and agricultural products. Evidence indicates that T-2 toxin induces apoptosis and autophagy. This study investigated the role of ferroptosis in T-2 toxin cytotoxicity. RAS-selective lethal compound 3 (RSL3) and Erastin were applied to initiate ferroptosis. RSL3- and Erastin-initiated cell death were enhanced by T-2 toxin. Treatment with the ferroptosis inhibitor ferrostatin-1 markedly restored the sensitizing effect of T-2 toxin to RSL3- or Erastin-initiated apoptosis, suggesting that ferroptosis plays a vital role in T-2 toxin-induced cytotoxicity. Mechanistically, T-2 toxin promoted ferroptosis by inducing lipid reactive oxygen species (ROS), as N-acetyl-l-cysteine significantly blocked T-2 toxin-induced ferroptosis. Moreover, T-2 toxin decreased the expression of solute carrier family 7 member 11 (SLC7A11) and failed to further enhance ferroptosis in SLC7A11-deficient cells. SLC7A11 overexpression significantly rescued the enhanced ferroptosis caused by T-2 toxin. T-2 toxin induces ferroptosis by downregulating SLC7A11 expression. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.

CRISPR/Cas9-Based Genome Editing Platform for Companilactobacillus crustorum to Reveal the Molecular Mechanism of Its Probiotic Properties.

Companilactobacillus crustorum usually serves as a starter culture for the food industry. Recent studies revealed that this species also possesses probiotic properties. Genome engineering, including point mutation or gene deletion, is desired to understand the mechanisms of its probiotic and fermentation properties. To tackle the hurdle in genetic manipulation in C. crustorum, here, we established a fast and easy CRISPR/Cas9-based platform for precise genome editing in this species. The platform includes two CRISPR/Cas9 systems and a CRISPR/Cas9-based editing system. Using the developed methods, we were able to knockout 12 genes in C. crustorum by deleting a fragment located in the open reading frames. The editing efficiency ranged from 14.3 to 100%. Moreover, we developed a CRISPR-assisted cytidine base-editing system, enabling programmed C to T conversion in the chromosome for gene inactivation or point mutation. To further exploit this platform, we investigated the role of nine putative bacteriocin-encoding genes and found that bacteriocins BM173 and BM1157 mostly contributed to the antimicrobial activity of C. crustorum MN047 against Staphylococcus aureus and Escherichia coli. In addition, the regulation of bacteriocin expression was also revealed to be linked with the quorum-sensing modulator luxS. This work will dramatically accelerate the genetic engineering of C. crustorum and close-related species.