Acid Degradation Research Articles

Increasing the Nutritional Value of Camelina Meal via Trametes versicolor Solid-State Fermentation with Various Co-Substrates

Upcycling low-cost agricultural by-products into valuable and sustainable alternative feeding materials could secure human food-supply chains with a low carbon footprint. This study explored increasing the feeding value of camelina meal (CAM) mixed with wheat bran (WB), soybean hulls (SH), and rice hulls (RH) for monogastric animals via solid-state fermentation (SSF) using white rot fungus Trametes versicolor. Experiments evaluated fungal growth, amino acid profiles, structural carbohydrates, glucosinolates, phytate and in vitro dry matter digestibility (IVDMD). Weight loss analysis indicated that fungal growth was more active in WB/CAM and SH/CAM substrates than RH/CAM. Significant phytic acid degradation and near-complete glucosinolate elimination improved CAM feed quality across all substrates. Fermentation increased total and essential amino acids in the SH/CAM mixture, while reductions occurred in WB/CAM and RH/CAM mixtures. SH/CAM fermentation caused substantial cellulose and hemicellulose degradation, resulting in a 44% IVDMD increase. Conversely, RH/CAM fermentation decreased IVDMD despite a reduction in cellulose, possibly due to protein degradation. This study demonstrates the potential of T. versicolor-mediated SSF to enhance CAM and other agricultural residues’ feeding value for monogastric animal applications.

Optimizing a modified cetyltrimethylammonium bromide protocol for fungal DNA extraction: Insights from multilocus gene amplification

Abstract Genomic DNA (gDNA) extraction is an important step in many molecular studies of fungal biology, and it is necessary to evaluate the efficiency, cost-effectiveness, and efficacy of different extraction methods to ensure successful amplification of the target gene and minimize deoxyribonucleic acid (DNA) degradation. The modified cetyltrimethylammonium bromide (CTAB) method was found to be effective in releasing high molecular weight gDNA with minimal protein contamination. Based on anticipated gDNA yield and quality, extraction time, cost effectiveness, successful amplification, and waste management, our findings serve as a guide for selecting techniques of gDNA extraction from fungal species. This study presents a modified CTAB method for extracting DNA from a variety of fungal species including Aspergillus, Penicillium, Alternaria, Dothiorella, and Fusarium. Comparison of three cell crushing methods reveals similar gDNA yields, demonstrating the method’s effectiveness. Furthermore, the modified CTAB method is cost-effective and safe, eliminating the need for grinding with liquid nitrogen or bead beating. The method has a potential use for nucleic-based fungal disease diagnosis such as fish fungal diseases, plant pathogens, fruit rot associated pathogens, and human fungal diseases as we were successful in PCR amplifying several gene loci from varied fungal pathogens.

Natural substrates and amphipods epibionts contaminated by microplastic

Amphipods inhabit microhabitats that protect them against predation, provide nutrition and an area for reproduction and development. However, the compounds of the ecosystem are impacted by the presence of microplastics (MPs), which are a threat to marine communities. Since the organisms interact with and ingest/filter the different quantities of MPs, and may make it available to the associated epibionts, three natural substrates (algae, sponges, and ascidians) were sampled to compare the number of MPs in them and in their associated amphipods. This study was conducted on rocky shores from Rio de Janeiro (Brazil), differently from other studies that have been focused on experimental tests. The samples were submitted to density separation to extract the microplastics and acid degradation to access MP in amphipods. Algae retained a greater concentration of MPs as a sink of particles, as well as its associated amphipods. Sponges and ascidians have different mechanisms to filter water, which influences the MPs accumulation in amphipods. Those associated with sponges and ascidians had fewer microplastic particles. This is the first study comparing the retention of MP in different natural substrates and their amphipod epibionts, which gives information about microplastic contamination in these microhabitats and their associated organisms.

Metabolomics, network pharmacology, and microbiome analyses uncover the mechanisms of the Chinese herbal formula for the improvement of meat quality in spent hens

BackgroundMeat originating from the spent hen is an important source of poultry meat production; however, multiple factors cause the decline in the meat quality of spent hens. Chinese herbs have been widely used as medicine for a long time to prevent diseases and as nutrient supplements to improve the product quality. This experiment explored the effects of adding 1.0% Chinese herbal formula (CHF, including 0.30% Leonurus japonicus Houtt., 0.20% Salvia miltiorrhiza Bge., 0.25% Ligustrum lucidum Ait., and 0.25% Taraxacum mongolicum Hand.-Mazz.) for 120 d to the spent hens’ diet through metabolomics, network pharmacology, and microbiome strategies.ResultsThe results indicated that CHF supplementation improved the meat quality by reducing drip loss (P < 0.05), b* value (P = 0.058), and shear force (P = 0.099) and increasing cooked meat percentage (P = 0.054) and dry matter (P < 0.05) of breast muscle. The addition of CHF improved the nutritional value of breast muscle by increasing (P < 0.05) the content of C18:2n-6, n-6/n-3 polyunsaturated fatty acids (PUFA), total PUFA, PUFA-to-saturated fatty acids (SFA) ratio, and hypocholesterolemic-to-hypercholesterolemic ratio, and tending to increase serine content (P = 0.069). The targeted metabolomics analysis revealed that the biosynthesis of SFA, linoleic acid metabolism, fatty acid degradation, fatty acid elongation, and fatty acid biosynthesis pathways were enriched by CHF supplementation. Furthermore, the network pharmacology analysis indicated that CHF was closely associated with oxidative stress and lipid metabolism. The CHF supplementation increased the glutathione peroxidase level (P < 0.05) and upregulated gene expression related to the Nrf2 pathway (including HO-1, P < 0.05; Nrf2, P = 0.098; CAT, P = 0.060; GPX1, P = 0.063; and SOD2, P = 0.052) and lipid metabolism (including PPARγ, P < 0.05; SREBP1, P = 0.059; and CPT1A, P = 0.058). Additionally, CHF supplementation increased Firmicutes and decreased Bacteroidetes, Spirochaetes, and Synergistetes abundances (P < 0.05), which may contribute to better meat quality.ConclusionsOur results suggest that CHF supplementation improved the quality and nutritional value of meat, which will provide a theoretical basis for the utilization of CHF as a feed additive in spent hens’ diets.Graphical

The role of ALDHs in lipid peroxidation-related diseases.

Lipid peroxidation presents the oxidative degradation of polyunsaturated fatty acids lincited by reactive species. Excessive accumulation of lipid peroxidation byproducts, including 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA), causes protein dysfunction and various illnesses. Aldehyde dehydrogenases (ALDHs) catalyze the metabolism of both endogenous and exogenous aldehydes. These enzymes participate in detoxification and intermediary metabolism. Contemporary research has affirmed the involvement of both enzymatic and non-enzymatic pathways of ALDHs in modulating the evolution of diseases associated with lipid peroxidation. This review provides an overview of the biological functions and clinical implications concerning the enzymatic and non-enzymatic pathways of ALDHs in diseases related to lipid peroxidation, such as, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, and type 2 diabetes (T2DM). Furthermore, the activators or inhibitors of ALDHs represent a promising therapeutic strategy for lipid peroxidation-related diseases.

Isolation, LC–MS/MS, NMR Characterization, In Silico Toxicity, and ADME Evaluation of Stress‐Degradation Products of Sunitinib With Optimized Stability‐Indicating HPLC Method for Quantification of Sunitinib and its Impurities

ABSTRACTSunitinib belongs to the tyrosine kinase inhibitors class of medical drugs prescribed to treat various types of cancers, including renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors by blocking the action of enzymes that promote cancer cell growth. Forced degradation studies are crucial for assessing drug stability and will be helpful in drug discovery and development. In this study, sunitinib underwent different stress testing according to ICH guidelines to identify and analyze its degradation products (DPs). The stress study findings proved that sunitinib is highly sensitive to acid (2DPs), base (1 DP), and oxidation (1 DP) degradation but remains stable in other stress conditions with significantly less degradation. The separation of sunitinib and its impurities and four DPs was achieved using a Waters XBridge C18 column (250 mm × 4.6 mm, 5 µm) with 0.7 mL/min gradient flow of ammonium formate buffer (pH 4.8) and acetonitrile with a detection wavelength of 258 nm. These conditions produce well‐retained and resolved peaks corresponding to sunitinib at 8.4 min, whereas 4.8, 3.5, and 1.9 min are noticed for impurities 1, 2, and 3, respectively. These study findings provide a comprehensive analysis of sunitinib, its impurities, and DPs, offering crucial insights into its stability and toxicity that can enhance drug development and safety profiling. The study also detailed the degradation pathway of sunitinib, its impurities, and the fragmentation patterns of DPs, which had not been previously reported in any other studies. All these four DPs belong to Class 4 (moderate) toxicity with distinct pharmacokinetic profiles. Hence, it can be concluded that these study findings provide a comprehensive analysis of sunitinib, its impurities, and DPs, offering crucial insights into its stability and toxicity that can enhance drug development and safety profiling.

Hydrocarbon biodegradation processes at a historic oil production site - A signature metabolite study.

Decades of research demonstrated that microbes can remediate petroleum-contaminated environments through biodegradation of hydrocarbons. Recent studies have applied signature metabolite analysis to investigate hydrocarbon-contaminated sites, focusing primarily on aquifer systems and metabolites of relatively water-soluble monoaromatic hydrocarbons. However, the number of studies involving non-targeted analysis and identification of individual metabolites in environmental samples is limited. In addition, metabolite patterns in crude oil-contaminated samples are rarely compared to those in the unaltered crude oils. In this study, we identified metabolites in complex environmental samples and crude oils from a former oil sands mining site using non-targeted gas chromatography-mass spectrometry. Based on these results, we suggest potential biodegradation processes that may account for the formation of the observed metabolites. The non-target results from water samples contaminated with crude oil showed that aromatic acids were the dominant metabolites. We observed that arylacetic acids were particularly abundant in the water samples when the metabolite patterns were compared with those found in crude oil and oil sands samples formerly produced at the site, as well as those found in oil-contaminated soil samples. The dominance of arylacetic acids is evidence that the microbial communities have a limited capacity for α-oxidation, i.e. an enzymatic attack on the methylene group, which is necessary to further degrade these compounds. Therefore, aromatic acids may be enriched at sites with long-term exposure to crude oil. Our study demonstrates that non-targeted metabolite analysis can provide an insight into the prevalent pattern of carboxylic acid metabolites and degradation processes in hydrocarbon-contaminated habitats.

CitGATA7 interact with histone acetyltransferase CitHAG28 to promote citric acid degradation by regulating the glutamine synthetase pathway in citrus

Organic acid is a crucial indicator of fruit quality traits. Citric acid, the predominant organic acid in citrus fruit, directly influences its edible quality and economic value. While the transcriptional regulatory mechanisms of citric acid metabolism have been extensively studied, the understanding about the transcriptional and epigenetic co-regulation mechanisms is limited. This study characterized a transcription factor, CitGATA7, which directly binds to and activates the expression of genes associated with the glutamine synthetase pathway regulating citric acid degradation. These genes include the aconitase encoding gene CitACO3, the isocitrate dehydrogenase encoding gene CitIDH1, and the glutamine synthetase encoding gene CitGS1. Furthermore, CitGATA7 physically interacts with the histone acetyltransferase CitHAG28 to enhance histone 3 acetylation levels near the transcription start site of CitACO3, CitIDH1, and CitGS1, thereby increasing their transcription and promoting citric acid degradation. The findings demonstrate that the CitGATA7-CitHAG28 protein complex transcriptionally regulate the expression of the GS pathway genes, i.e., CitACO3, CitIDH1, and CitGS1, via histone acetylation, thus promoting citric acid catabolism. This study establishes a direct link between transcriptional regulation and histone acetylation regarding citric acid metabolism, providing insights for strategies to manipulate organic acid accumulation in fruit.

Green chemistry in chemical mechanical planarization through a comparison of amino acid degradability with benzotriazole in advanced oxidation processes

Green chemistry in chemical mechanical planarization through a comparison of amino acid degradability with benzotriazole in advanced oxidation processes

Promoting effect of oxygen vacancies in CuZnOx-2/peroxymonosulfate system on the p-arsanilic acid degradation and secondary arsenic species immobilization

Combining chemical oxidation and adsorption is highly desirable but challenging to remove organoarsenic compounds for water purification. Herein, we prepared a Zn-doped CuO (CuZnOx-2) catalyst by incorporating Zn atoms into the CuO lattice, which results in abundant surface oxygen vacancies (OVs) and modulates the electronic structure of Cu-OVs-Zn sites for PMS activation to degrade p-arsanilic acid (p-ASA) and adsorb the secondary arsenic species simultaneously. The elevated d-band centers for Cu upward to the Fermi level can significantly strengthen the adsorption of PMS, p-ASA, and the generated arsenic species. The OVs cause the charge redistribution to form electron-rich centers, which accelerate the electron transfer from Cu-OVs-Zn sites to adsorbed PMS, facilitating the cleavage of peroxide bond to produce SO4•-, •OH. Furthermore, the PMS adsorbed on the local environment of OVs with different configurations can directly decompose to produce 1O2 without undergoing PMS → O2•- → 1O2 or O2 → O2•- → 1O2 processes. The evolution process of the main arsenic species in solution and catalyst surface with oxidation was clarified. The ultimate removal of the total As involves 20% As(III), 60% As(V), and 20% organic arsenic intermediates via forming inner-sphere complexes or electrostatic interaction. This contribution provides a brand-new perspective for the remediation of organoarsenic pollution over designing highly active catalysts.

Soybean bioactive peptide supplementation improves gut health and metabolism in broiler chickens.

This study aimed to investigate the effects of soybean bioactive peptide (SBP) on the growth performance and intestinal health of yellow-feathered broilers and to further elucidate the regulatory mechanisms of intestinal health using multi-omics analysis. A total of 320 1-day-old yellow-feathered broilers were randomly divided into two groups, with 10 replicates per group and 16 birds per replicate. Broilers in the control group received the basal diet, and those in the experimental group (SBPG) received the basal diet with 0.2 % SBP replacing the same amount of soybean meal. The experiment lasted for 70 d. The results showed that, compared with those in the control group, the final body weight and average daily gain of SBPG broilers were significantly higher (P < 0.05), and the feed conversion ratio was significantly lower (P < 0.05). Notably, SBP significantly improved gut health in chickens, including increased intestinal villus height, decreased levels of proinflammatory factors, such as IL-1β and interferon-γ, and upregulated expression of tight junction proteins, such as ZO-1 and occludin. In addition, transcriptome sequencing results revealed that broilers in the SBP group exhibited significant enrichment in multiple metabolic pathways, including fatty acid metabolism, fatty acid degradation, and the biosynthesis of unsaturated fatty acids (P < 0.05). Cecal 16S rRNA sequencing showed that SBPG increased the abundance of the butyrate-producing beneficial bacteria Muribaculaceae. Subsequent cecal metabolome analysis also revealed that SBPG enhanced lipid-related metabolic pathways, such as alpha-linolenic acid metabolism and GPI-anchor biosynthesis. In conclusion, SBP is a potential feed additive that can improve intestinal morphology, enhance intestinal immunity and barrier function, optimize the structure of the intestinal microbiota, and enhance metabolic function.

Process performance of in-situ bio-methanation for co-digestion of sewage sludge and lactic acid, aiming to utilize waste poly-lactic acid as methane

This study examined hydrogen conversion efficiency and operational stability in pilot-scale in-situ bio-methanation during the co-digestion of sewage sludge and lactic acid (partially derived from waste poly-lactic acid). Parallel laboratory-scale experiments were also conducted. In the pilot, hydrogen conversion efficiency decreased from 98.9 % to 84.4 % as the hydrogen feed rate increased from 240 to 1,200 mL/LR/d. Conversely, laboratory experiments maintained efficiencies above 95 % at a feed rate of 3,600 mL/LR/d, suggesting that hydrogen gas–liquid transfer limited hydrogen conversion efficiency in the pilot. Lactic acid degradation was observed both with and without hydrogen injection in the pilot. Methane yields from the acid were 310 ± 30 and 300 ± 30 mL/g (chemical oxygen demand (COD))-added, close to the theoretical methane yield (350 mL/gCOD). These results demonstrate the importance of hydrogen gas–liquid transfer when scaling up bio-methanation processes. Moreover, they showed the potential of waste poly-lactic acid as a methane source.

Degradation of Oxolinic Acid in Soil Under Simulated Natural Degradation Processes

Oxolinic acid (OA), a quinolone-class antibiotic commonly used in domestic agriculture, exhibits low bioavailability, raising concerns about its potential environmental persistence. Residual OA in the environment can undergo partial degradation through natural processes, which are influenced by various factors. This study aimed to investigate the photodegradation and biodegradation patterns of OA under various environmental factors, including temperature, light intensity, soil usage, soil organic matter content (OM). Additionally, adsorption and desorption experiments were conducted to elucidate the relationship between OA degradation and its adsorption-desorption behavior in soil. In this study, two UV-A intensities (2.3 and 1.5 mW cm&lt;sup&gt;-2&lt;/sup&gt;) and two temperatures (21.8 and 35.0&lt;sup&gt;o&lt;/sup&gt;C) were applied to examine the OA degradation behavior. Biodegradation tests were conducted using soil samples with varying land uses (rice paddy, field) and OM (6.4% and 2.3%). Additionally, sorption tests were performed using the soil samples and OA solutions, followed by desorption tests on the OA-sorbed soil samples. In the photodegradation experiment, the OA degradation rate ranged from 16.6% to 51% across all conditions after 20 d. Compared to other antibiotics reported in previous studies, OA exhibited relatively slow photodegradation, and the variations in degradation rates under the tested experimental conditions were not statistically significant. In the case of biodegradation, similar degradation rates were observed in the field and rice paddy soils, with faster degradation occurring in soils with lower OM. The differing biodegradation patterns observed across soil samples could be partially explained by the adsorption-desorption characteristics of OA in soils. The degradation of antibiotics through simulated natural processes such as photodegradation and biodegradation did not exhibit consistent trends depending on the environmental factors or soil properties. This suggests that the degradation of antibiotics is a complex process influenced by various factors, including, but not limited to, environmental factors and soil properties. This study highlights the need for further research to better understand the behavior of residual antibiotics in soil environments.

Complete shielding of multivitamins to reduce toxic peroxides in the parenteral nutrition (C-SMART-PN): A randomized controlled pilot study.

When exposed to ambient light, parenteral nutrition (PN) contamination with peroxides almost doubles, which increases oxidative stress in preterm infants, contributing to the development of bronchopulmonary dysplasia. The American Society for Parenteral and Enteral Nutrition (ASPEN) recommends complete PN photoprotection to reduce peroxide contamination and optimize its integrity but acknowledges the challenges of its implementation. In this study, a novel photoprotection procedure was tested for its effectiveness in reducing peroxide load and limiting ascorbic acid degradation, and for its feasibility and effectiveness in reducing urinary peroxide levels in preterm infants. In vitro evaluation included neonatal lipid injectable emulsion-free PN admixtures prepared and infused according to current practice or the suggested photoprotection procedure through separation and complete shielding of intravenous multivitamin preparation from compounding to administration through photoprotected infusion sets. In vivo evaluation included a single-center randomized controlled pilot study of extremely preterm infants receiving PN according to current practice or the suggested photoprotection procedure. In vitro, photoprotection allowed a 44% decrease in peroxide generation (P < 0.001) and reduced by half ascorbic acid degradation in PN admixtures (P < 0.001). In vivo, 28 infants completed the study. Baseline urinary peroxide levels were similar in both groups before PN initiation, and the suggested photoprotection procedure resulted in a significant decrease in urinary peroxide levels over the first week of life (P < 0.05). The suggested procedure appears feasible and effective in reducing peroxide contamination and optimizing PN integrity, representing a step toward integrating complete photoprotection of PN as the standard of care in preterm infants.

Biomimetic degradation of perfluorinated acids by vitamin B12 with nano-zero-valent iron/nickel bimetal: effects of their self-structure and coexisting substances

Biomimetic degradation of perfluorinated acids by vitamin B12 with nano-zero-valent iron/nickel bimetal: effects of their self-structure and coexisting substances

Enhancing Probiotic Viability in Yogurt: The Role of Apple Fibers in Supporting Lacticaseibacillus casei ATCC 393 During Storage and Gastrointestinal Transit

Probiotics are widely recognized for their health benefits, but their viability during food processing and digestion poses significant challenges. The present study evaluated the impact of incorporating apple fibers into yogurt on the viability of the probiotic strain Lacticaseibacillus casei ATCC 393 during production, storage, and simulated gastrointestinal digestion. Apple fibers, a by-product of apple processing, were used as a prebiotic ingredient due to their functional and technological benefits. The incorporation of apple fibers increased probiotic viability during 28 days of refrigerated storage, improving it from 90.4% in the control yogurt to 93.9%. Under simulated gastrointestinal conditions, yogurt alone acted as a protective matrix, preserving probiotic viability, during gastric (71.0% at pH 2 after 3 h) and intestinal digestion (73.3% at 0.3% bile salts after 6 h). The inclusion of apple fibers further enhanced this protection, reducing probiotic viability loss in both gastric (81.9% at pH 2 after 3 h) and intestinal (79.0% at 0.3% bile salts after 6 h) environments. Similar results were obtained using the INFOGEST 2.0 static protocol. After the completion of the protocol (oral, gastric and intestinal phase) a viability of 71.1% (6.61 logCFU/g) was observed in the yogurt with apple fibers compared to 64.5% (6.10 logCFU/g) in the control yogurt. This enhanced protection could be attributed to the potential prebiotic properties of apple fibers, including their pectin and cellulose content, which may shield probiotics from acidic and enzymatic degradation. These findings highlight the potential of apple fiber-enriched yogurt as a functional food that supports probiotic viability during storage and throughout gastrointestinal transit. These insights may open the way for developing new food products with enhanced health benefits, aligning with growing consumer demand for functional foods.

Identification of core biomarkers for tuberculosis progression through bioinformatics analysis and in vitro research

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global public health issue with high mortality rates and challenges posed by drug-resistant strains, emphasizing the continued need for new therapeutic targets and effective treatment strategies. Transcriptomics is a highly effective tool for the development of novel anti-tuberculosis drugs. However, most studies focus only on changes in gene expression levels at specific time points. This study screened for genes with altered expression patterns from available transcriptomic data and analysed their association with the TB progression. Initially, a total of 1228 genes with altered expression patterns were identified through two-way analysis of variance (ANOVA). We define genes with a P-value less than 0.05 for the combined effect of infection and time on gene expression as those with altered expression patterns. Gene Ontology (GO) enrichment analysis revealed that the biological functions of these genes mainly involve DNA translation, RNA processing, and transcriptional regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that these genes are primarily associated with fatty acid degradation, pyruvate metabolism, arginine and proline metabolism, as well as cholesterol metabolism signaling pathways. Subsequent Protein-protein interaction (PPI) analysis and Receiver Operating Characteristic (ROC) curve analysis identified four core genes closely associated with TB progression, namely Rac Family Small GTPase 1 (RAC1), Ring-Box 1 (RBX1), Mitochondrial Ribosomal Protein L33 (MRPL33), and ELAV Like RNA Binding Protein 1 (ELAVL1). Q-PCR experiments confirmed that Mtb infection led to changes in the gene expression patterns of RAC1, RBX1, MRPL33, and ELAVL1 in THP-1 cells. These four genes may serve as core biomarkers for TB progression and can be utilized in the development of more effective anti-tuberculosis drugs and host therapy.

DOP019 Reduced Gut Microbial Amino Acid Auxotrophies and Enhanced Tryptophan Degradation in Inflammatory Bowel Disease

Abstract Background Microbial amino acid auxotrophies, the inability of certain gut bacteria to synthesise essential amino acids, are important microbiome features contributing to gut microbial diversity and stability.1 Their relationship with inflammatory bowel disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD), remains poorly understood. Methods Stool and serum samples were collected from healthy controls (HC, n=190) and IBD patients from two longitudinal biologic therapy exposure (Baseline, Week 14) cohorts in Kiel, Germany (nUC=26, nCD=29) and Leuven, Belgium (nUC=63). Additional stool metagenomes from a Boston, US cohort (nUC=49, nCD=65) were included. Stool DNA underwent shotgun metagenomic sequencing. Metagenomic data were processed with the ATLAS workflow for metagenome-assembled genomes (MAGs) inference and quantification. Serum metabolomes were analysed using the Biocrates MxP Quant 500 Kit. Microbial auxotrophies and amino acid degradation pathways were predicted using genome-scale metabolic modelling.2 Results Amino acid auxotrophies were prevalent in the human gut microbiome, with Tryptophan (Trp) auxotrophies being the most common. Patients with IBD showed reduced auxotrophies compared to HC, with CRP levels correlating with more pronounced reductions in Trp auxotrophies. Metagenomic profiling revealed a distinct enrichment of amino acid degradation genes in IBD, particularly for Trp-degrading enzymes such as Tryptophan decarboxylase and Tryptophan transaminase. These changes correlated with specific serum metabolites, particularly aromatic compounds, indicating a strong interconnection between microbial and host amino acid metabolism. Conclusion Altered microbial metabolism in IBD is characterised by reduced Trp auxotrophies and increased Trp degradation. This suggests a microbial imbalance where Trp degraders outcompete auxotrophic genotypes, potentially contributing to IBD pathology. Understanding the shifts in amino acid requirements and degradation by the gut microbiome provides new insights into microbiome-host co-metabolism in IBD and may inform future therapeutic strategies targeting nutrient essentialities of gut microorganisms.

Transcriptomic characterization of the functional and morphological development of the rumen wall in weaned lambs fed a diet containing yeast co-cultures of Saccharomyces cerevisiae and Kluyveromyces marxianus.

In lambs, the function of the rumen is incompletely developed at weaning, and the inclusion of yeast cultures in the diet can profoundly influence the morphological and functional development of the rumen. In this study, the effects of Saccharomyces cerevisiae and Kluyveromyces marxianus (NM) yeast co-cultures on ruminal histomorphology were assessed, and corresponding transcriptomic changes within the rumen epithelium were identified. In total, 24 lambs were grouped into four groups of six lambs including a control (C) group fed a basal diet, and N, M, and NM groups in which lambs were fed the basal diet, respectively, supplemented with Saccharomyces cerevisiae yeast cultures (30 g/d per head), Kluyveromyces marxianus yeast cultures (30 g/d per head), and co-cultures of both yeasts (30 g/d per head), the experiment lasted for 42 d. In morphological analyses, lambs from the NM group presented with significant increases in papilla length, papilla width, and epithelial thickness in the rumen relative to lambs in the C group (p < 0.05). Transcriptomic analyses revealed 202 genes that were differentially expressed between samples from the C and NM groups, with the largest proportion of these genes being associated with the oxidative phosphorylation pathway. In a weighted gene coexpression network analysis, a positive correlation was observed between the MEgreen and MEpurple modules and rumen morphology. Of these modules, the MEgreen module was found to be more closely linked to fatty acid metabolism and oxidative phosphorylation, whereas the MEpurple module was linked to oxidative phosphorylation and fatty acid degradation. Ultimately, these results suggest that dietary supplementation with NM has driven the degradation of fatty acids, the induction of oxidative phosphorylation, the acceleration of lipid metabolism, the production of ATP to sustain ruminal growth, and the maintenance of intracellular NADH/NAD+ homeostasis on weaned lambs and is superior to single yeast fermentation. These results thus offer a theoretical foundation for further studies examining the mechanisms through which NM cultures can influence ruminal development in lambs.

Itaconate mechanism of action and dissimilation in Mycobacterium tuberculosis

Itaconate, an abundant metabolite produced by macrophages upon interferon-γ stimulation, possesses both antibacterial and immunomodulatory properties. Despite its crucial role in immunity and antimicrobial control, its mechanism of action and dissimilation are poorly understood. Here, we demonstrate that infection of mice with Mycobacterium tuberculosis increases itaconate levels in lung tissues. We also show that exposure to itaconate inhibits M. tuberculosis growth in vitro, in macrophages, and mice. We report that exposure to sodium itaconate (ITA) interferes with the central carbon metabolism of M. tuberculosis. In addition to the inhibition of isocitrate lyase (ICL), we demonstrate that itaconate inhibits aldolase and inosine monophosphate (IMP) dehydrogenase in a concentration-dependent manner. Previous studies have shown that Rv2498c from M. tuberculosis is the bona fide (S)-citramalyl-CoA lyase, but the remaining components of the pathway remain elusive. Here, we report that Rv2503c and Rv3272 possess itaconate:succinyl-CoA transferase activity, and Rv2499c and Rv3389c possess itaconyl-CoA hydratase activity. Relative to the parental and complemented strains, the ΔRv3389c strain of M. tuberculosis was attenuated for growth in itaconate-containing medium, in macrophages, mice, and guinea pigs. The attenuated phenotype of ΔRv3389c strain of M. tuberculosis is associated with a defect in the itaconate dissimilation and propionyl-CoA detoxification pathway. This study thus reveals that multiple metabolic enzymes are targeted by itaconate in M. tuberculosis. Furthermore, we have assigned the two remaining enzymes responsible for the degradation of itaconic acid into pyruvate and acetyl-CoA. Finally, we also demonstrate the importance of enzymes involved in the itaconate dissimilation pathway for M. tuberculosis pathogenesis.