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PubMed2026

Effects of Acalypha australis L. Extract on Growth Performance, Antioxidant Capacity and Intestinal Microbial Composition in Weaned Piglets.

The objective of this study was to investigate the effects of Acalypha australis L. extract (ALE) on the growth performance and intestinal health in piglets. A total of 24 weaned piglets were randomly allocated to three groups: the control group (CON), which was fed a basal diet, and the ALE0.5 and ALE1.0 groups, which were fed the basal diet supplemented with 0.5 and 1.0 g/kg of ALE, respectively. The measured variables included growth performance, digestive enzyme activity, intestinal morphology, antioxidant capacity, and intestinal microbiota and metabolites. The results showed that, compared to the CON group, supplementation of 1.0 g/kg ALE in the diets of weaned piglets significantly increased the ratio of gain to feed from 15 to 21 days (p < 0.05), decreased the diarrhea rate from Days 15 to 21 and Days 0 to 21 (p < 0.05), and increased the activities of pancreatic α-amylase, lipase, trypsin, and chymotrypsin, as well as duodenal α-amylase, lipase, and trypsin, and jejunal maltase and sucrase (p < 0.05). Additionally, supplementation of 1.0 g/kg ALE in the diet significantly improved the intestinal morphology of the duodenum and jejunum, as well as the expression of intestinal barrier-related genes in the small intestine (p < 0.05). Moreover, it significantly increased serum glutathione peroxidase activity and jejunal and ileal superoxide dismutase activities (p < 0.05), and also significantly increased the colonic propionic acid concentration of piglets (p < 0.05). The ALE supplementation increased the abundance of the colonic marker bacteria Collinsella in the piglets and influenced pathways related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. ALE can serve as a potential natural feed additive to regulate the structure of intestinal microbiota and metabolic pathways, enhance antioxidant capacity, improve intestinal health, reduce diarrhea incidence, and ultimately promote the growth performance of piglets.

Acalypha australis L. extract↗

PubMed2026

Genome-scale insights into metabolic streamlining and photosynthetic energy balance in the extremophile green alga Picocystis salinarum (Picocystophyceae, Chlorophyta).

Picocystis salinarum is an early-diverging chlorophyte and the sole described member of the Picocystophyceae, frequently dominating hypersaline and alkaline lakes despite extreme physicochemical constraints. To elucidate the genomic foundations of its ecological success, we generated a fully annotated, chromosome-scale nuclear genome assembly of the type strain originally isolated from a saline pond in San Francisco Bay. The 18.5-Mb genome comprises 30 chromosomal assemblies, exhibits clear diploidy, and contains multiple copies of intact Ty3/Gypsy and Ty1/Copia long terminal repeat retrotransposons encoding polyproteins with atypical accessory domains. Phylogenomic analyses reveal strong affinity with the Nephroselmidophyceae. Comparative analyses reveal extensive metabolic streamlining, including the absence of a queuosine salvage pathway, the 2-methylcitrate cycle, β-oxidation of propionate, and branched-chain amino acid catabolism, traits retained in several marine prasinophyte lineages. In contrast, the genome preserves multiple ancestral bacterial derived systems. Notably, P. salinarum features a complete chloroplast NADH dehydrogenase-like complex, including all membrane, electron binding, and assembly components, a configuration not previously reported in sequenced chlorophyte algae. This retention implies substantial capacity for cyclic electron flow and chlororespiration, processes expected to be critical in chronically low-light and chemically extreme environments. The genome further reveals a distinctive biochemical CO2-concentrating mechanism centered on plastid-targeted phosphoenolpyruvate carboxykinase, complete plastid peptidoglycan biosynthetic and remodeling pathways, and partial retention of lipid-A-related machinery. Conversely, P. salinarum lacks canonical non-photochemical quenching proteins while retaining xanthophyll-cycle enzymes that support slower photoprotective responses. Together, these features define a coordinated genomic architecture that underpins the specialization of P. salinarum to hypersaline, alkaline, and persistently low-light ecosystems.

3‐deoxy‐D‐manno‐octulo↗

PubMed2025

The homeostasis of β-alanine is key for Arabidopsis reproductive growth and development.

β-Alanine, an abundant non-proteinogenic amino acid, acts as a precursor for coenzyme A and plays a role in various stress responses. However, a comprehensive understanding of its metabolism in plants remains incomplete. Previous metabolic genome-wide association studies (mGWAS) identified ALANINE:GLYOXYLATE AMINOTRANSFERASE2 (AGT2, AT4G39660) linked to β-alanine levels in Arabidopsis under normal conditions. In this study, we aimed to deepen our insights into β-alanine regulation by conducting mGWAS under two contrasting environmental conditions: control (12 h photoperiod, 21°C, 150 μmol m-2 sec-1) and stress (harvested after 1820 min at 32°C and darkness). We identified two highly significant quantitative trait loci (QTL) for β-alanine, including the AGT2 locus associated in both environments and ALDEHYDE DEHYDROGENASE6B2 (ALDH6B2, AT2G14170) associated only under stress conditions. A coexpression-correlation network revealed that the regulatory pathway involving β-alanine levels, AGT2, and ALDH6B2 connects the branched chained amino acid (BCAA) degradation through the propionate pathway. Metabolic profiles of AGT2 overexpression (OE) and knock-out (KO) lines (agt2) across various organs and developmental stages established the critical role of AGT2 in β-alanine metabolism. This work underscores the importance of β-alanine homeostasis for proper growth and development in Arabidopsis.

Arabidopsis↗

PubMed2026

Isolation, genomic characterization, and safety assessment of an O-desmethylangolensin-producing Clostridium beijerinckii strain from Chinese Stinky Tofu.

The health benefits of dietary soy isoflavones are largely mediated by specific microbial metabolites, such as O-desmethylangolensin (O-DMA). However, the diversity and application potential of O-DMA-producing strains remain poorly explored, primarily due to the limited availability of isolated strains, narrow ecological sources, and a lack of practical applications. In this study, an O-DMA-producing bacterium, designated strain FRJF5, was isolated from Chinese stinky tofu under anaerobic conditions and was identified as Clostridium beijerinckii. The biosynthesized O-DMA exhibited an enantiomeric excess (e.e.) of 78.6%. Based on phylogenetic and average nucleotide identity analyses against 235 public C. beijerinckii genomes, the clustering of FRJF5 with strains from diverse habitats-including industrial fermentation settings, animal feces, and soil-highlights the broad ecological diversity within this species. Functional gene mining and intra-species comparative genomics revealed a unique flavonoid metabolism gene cluster in FRJF5. Using apigenin as a representative flavonoid, we confirmed the successful conversion to 3-(4-hydroxyphenyl)-propionic acid. Moreover, the strain was predicted and verified to possess a substantial butyrate-producing capacity. Genomic screening for virulence or antibiotic resistance genes, combined with phenotypic tests (hemolysis, antibiotic susceptibility, and mouse gavage), revealed a favorable safety profile for strain FRJF5. Finally, intervention experiments in a mouse model of colitis supported its potential in alleviating the disease. Collectively, this study identifies C. beijerinckii FRJF5 as a strain capable of simultaneously producing O-DMA and butyrate, highlighting its potential for future applications in functional foods.IMPORTANCESoy isoflavones require gut bacterial conversion into bioactive metabolites-such as the anti-inflammatory compound O-desmethylangolensin (O-DMA)-to exert health benefits. Yet O-DMA-producing strains remain scarce, largely confined to fecal sources, and poorly characterized. Here, we isolated Clostridium beijerinckii FRJF5 from Chinese stinky tofu, an unexplored ecological niche. This strain not only produces enantiomerically enriched O-DMA but also co-produces butyrate, a metabolite known to strengthen gut barrier function. Genomic mining uncovered a unique flavonoid metabolism gene cluster responsible for this dual activity. Combined with favorable safety profiles, FRJF5 emerges as a strong candidate for functional food applications. This work expands the known diversity of O-DMA producers and bridges traditional fermented foods with next-generation probiotic development.

O-desmethylangolensin↗

PubMed2025

Consumption of traditional Sardinian fermented milk promotes changes in the rat gut microbiota composition and functions.

BACKGROUND: Fermented milk products are part of the staple diet for many Mediterranean populations. Most of these traditional foods are enriched with lactobacilli and other lactic acid bacteria, as well as with metabolites resulting from lactose fermentation. Currently, there is very little scientific knowledge on how dietary supplementation with fermented milk affects the composition of the gut microbiota and its metabolic activities. RESULTS: We integrated 16 S rRNA gene-based taxonomic profiling with metaproteomics-based functional analysis to investigate gut microbiota changes in rats exposed to an 8-week dietary supplementation with casu axedu, a traditional fermented milk produced within rural communities in Sardinia (Italy). Several microbial taxa showed a significantly increased abundance at the end of the dietary treatment, including Phascolarctobacterium, Prevotella, Blautia glucerasea, and Lactococcus lactis, while Bacteroides dorei and Helicobacter rodentium were decreased compared to the control rats. Metaproteomic analysis highlighted a striking reshaping of the Prevotella proteome in agreement with its blooming in casu axedu-fed animals, suggesting an increase of the glycolytic activity through the Embden-Meyerhof-Parnas pathway over the Entner-Doudoroff pathway. Moreover, an increased production of enzymes involved in succinate biosynthesis was observed, which in turn significantly boosted the abundance of Phascolarctobacterium and its production of propionate. Fermented milk consumption also promoted microbial synthesis of branched chain essential amino acids L-valine and L-leucine. Finally, metaproteomic data indicated a reduction of bacterial virulence factors and host inflammatory markers, suggesting that the consumption of casu axedu can have beneficial effects on the gut mucosa health. CONCLUSIONS: Our integrated multi-omics approach reveals that dietary supplementation with the traditional Sardinian fermented milk, casu axedu, induces significant shifts in the rat gut microbiota composition and function, characterized by the enrichment of beneficial taxa and metabolic pathways associated with improved gut health and reduced inflammation.

Animals↗

PubMed2025

Association of metabolic dysregulation with treatment response in rectal cancer patients undergoing chemoradiotherapy.

BACKGROUND: This study aimed to explore the metabolic changes during neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) by serum metabolomics analysis, and to provide new biomarkers for individualized treatment and efficacy prediction. METHODS: Serum samples from 20 patients with LARC before, during and after NCRT were collected for metabolomic analysis. The metabolites in the serum samples were analyzed qualitatively and quantitatively using gas chromatography-mass spectrometry (GC-MS). Meanwhile, the differences in metabolic profiles at different time points were compared and significantly changed metabolites were screened. RESULTS: The metabolic profiles of patients were significantly altered at different time points of NCRT. Through metabolomic analysis, we identified metabolites that were significantly altered during NCRT and revealed alterations in the associated metabolic pathways. The predictive power of pre-radiotherapy isocitric acid and pro-radiotherapy 3-hydroxy-3-(4'-hydroxy-3'-methoxyphenyl) propionic acid in distinguishing patients sensitive and non-sensitive to NCRT was markedly high, with AUC values of 0.875 and 0.75, respectively. Additional analysis indicated that a combined panel of serum metabolites yielded even higher AUC values, thereby enhancing the accuracy of predicting the efficacy of neoadjuvant NCRT. CONCLUSION: This study revealed metabolic changes and corresponding alterations in metabolic pathways during NCRT in patients with LARC by serum metabolomic analysis. The metabolic disorders may be associated with poor outcomes in patients treated with NCRT for rectal cancer, providing new biomarkers for individualized treatment and prognostic assessment. Further studies and validation will help to gain insight into the mechanism of these metabolic changes and provide more basis for clinical application.

Humans↗

PubMed2026

Metabolic Engineering of Probiotic Saccharomyces boulardii Enables Intestinal 3-Hydroxybutyrate Delivery and Alters Short-Chain Fatty Acid Profiles in Mice.

3-Hydroxybutyric acid (3-HB) is a bioactive ketone body involved in the regulation of intestinal inflammation and metabolic homeostasis. Although engineered bacterial probiotics have been developed for localized 3-HB delivery, their susceptibility to antibacterial antibiotics may limit their use during concurrent antibiotic treatment. The probiotic yeast Saccharomyces boulardii offers an alternative host for intestinal 3-HB delivery because of its compatibility with antibacterial antibiotics and the availability of well-established genetic engineering tools. Here, we engineered S. boulardii for 3-HB production using Cas9-mediated genome editing. A heterologous 3-HB biosynthetic pathway was introduced into S. boulardii MYA-797, and endogenous acetyl-CoA and ethanol metabolism was subsequently rewired by overexpressing ACS1, deleting ADH1, and overexpressing ADH7. The optimized strain, SbDY02, produced 1.7 g/L 3-HB under microaerobic conditions. Oral administration of SbDY02 to C57BL/6J mice increased fecal 3-HB and short-chain fatty acid (SCFA) concentrations by 1.89-fold and 1.68-fold, respectively, compared with mice receiving the parental strain. Repeated administration also increased fecal acetate and circulating total SCFAs, butyrate, and propionate. In human colonic epithelial cells, purified 3-HB attenuated lipopolysaccharide-induced p38 MAPK phosphorylation, supporting its direct activity toward inflammation-associated epithelial signaling. To our knowledge, this study provides the first demonstration of a 3-HB-producing probiotic yeast and links central metabolic engineering of S. boulardii with increased 3-HB availability, altered SCFA profiles, and a host-relevant epithelial response.

3-hydroxybutyrate↗

PubMed2025

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Modulating Protein-Bound Uremic Toxins and Gut Microbiota in Predialysis CKD Patients: Matched Case-Control Study.

KEY POINTS: A reduction of indoxyl sulfate, p-cresyl sulfate, and several short-chain fatty acids was seen in sodium-glucose cotransporter-2 inhibitor-treated CKD patients. Variations in gut microbiota composition are correlated with levels of gut-derived uremic toxins in sodium-glucose cotransporter-2 inhibitor-treated CKD patients. BACKGROUND: The intricate interplay between CKD and intestinal microbiota has gained increasing attention, with gut dysbiosis being implicated in uremic toxin accumulation and CKD progression. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are now transforming CKD management but pose uncertain effects on shaping gut microbiota. This study aimed to elucidate the effect of SGLT2i on perturbations of gut microbial composition and metabolic responses in patients with CKD. METHODS: Analysis of fecal microbiota and targeted profiling of serum short-chain fatty acids and gut-derived uremic toxins were conducted in a matched case-control study, including 60 patients with CKD (treated: n=30; untreated: n=30) and 30 non-CKD controls. RESULTS: Gut microbial composition differed significantly among the three study groups. Patients with CKD receiving SGLT2i exhibited distinctive taxonomic profiles, such as enrichment of Bacteroides stercoris and Bacteroides coprocola. Surveys of metabolomic profiles revealed a reduction of two uremic solutes, indoxyl sulfate and p-cresyl sulfate (pCS), and several short-chain fatty acids (formic, acetic, propionic, valeric, and 2-methylbutanoic acid) in SGLT2i-treated CKD patients. Co-occurrence analysis demonstrated a set of intestinal microbes that is positively or negatively correlated with the levels of pCS, and the abundance of these pCS-associated intestinal microorganisms was correlated with the levels of indoxyl sulfate and isovaleric acids in the same and opposite direction, respectively. Further functional prediction indicated attenuated pathways related to protein and carbohydrate metabolism. CONCLUSIONS: Treatment with SGLT2i in patients with CKD is associated with distinct gut microbial composition and metabolite profiles, suggesting potential modulation of gut dysbiosis and metabolic pathways. Further studies are warranted to elucidate the clinical implications of these findings in CKD management.

CKD↗

PubMed2026

Defined human Clostridia consortia reverse colitis via dual effects of tryptophan metabolites on microbiota and immunity.

Microbial dysbiosis and disrupted mucosal immune homeostasis are integrally involved in the pathogenesis of inflammatory bowel diseases (IBDs). Live biotherapeutic products (LBPs) offer a potential therapeutic strategy to restore beneficial microbes and mitigate disease. We investigated the therapeutic efficacy of 2 LBPs, human Clostridia consortia 17-mix and 11-mix, by treating established colitis in murine models. Both LBPs exhibited therapeutic effects in T cell-mediated chronic colitis models induced by human microbiota and in pathobiont-driven gnotobiotic colitis models established with combinations of IBD-relevant human-derived strains. Metagenomic and metabolomic analyses elucidated mechanisms that go beyond established functions driven by short-chain fatty acids (SCFAs) and interleukin (IL)-10-producing regulatory T cells. Notably, LBPs exerted therapeutic effects by directly inhibiting resident pathobionts and through IL-10-independent activation of host anti-inflammatory aryl hydrocarbon receptor (AhR) pathways by bacterial tryptophan metabolites. These results elucidate SCFA- and IL-10-independent protective mechanisms exerted by defined resident bacterial strains that are depleted in IBD dysbiosis.

Animals↗

PubMed2026

Sex-specific expression of detoxification proteins contributes to differential metabolic detoxification capacity and acaricide sensitivity in female and male Tetranychus cinnabarinus (Boisduval).

Pronounced sex-specific differences exist in the toxicological traits of spider mite species. Our previous work showed that female Tetranychus cinnabarinus exhibit significantly higher tolerance to acaricides than males, primarily driven by elevated detoxification enzyme activity. However, the molecular basis underlying this sex-specific difference remains unclear. Here, we used pyridaben and cyflumetofen as representative acaricides to dissect the molecular mechanisms underlying sex-specific differences in detoxification metabolism between female and male mites. After 48 h of cyflumetofen exposure, GST activity increased significantly in female mites. Following pyridaben exposure, the activities of both P450 (24 h and 48 h) and CCE (48 h) increased significantly in female mites. Under the same conditions, only P450 activity increased significantly in male mites after 48 h of pyridaben exposure. Proteomic profiling identified 33 differentially expressed detoxification enzymes, predominantly from the major detoxification families P450, GST, and CCE; among them, 26 were significantly upregulated in females relative to males. Six detoxification enzymes, including CYP392A3, CYP389C5, TcGSTd02, TcGSTd13, TcCCE39, and TcCCE52, were selected for functional characterization. We successfully obtained six active recombinant detoxification enzymes through heterologous expression. IC50 and in vitro metabolism assays showed that these recombinant proteins display both shared and distinct capacities for metabolizing or sequestering cyflumetofen and pyridaben. RNAi and bioassay results demonstrated that silencing CYP389C5, TcGSTd02, and TcCCE52 resulted in more pronounced changes in acaricide susceptibility in female than in male mites. Collectively, this study demonstrates that the sex-biased protein abundance identifies candidate biochemical contributors to differential susceptibility in female and male mites.

Animals↗

PubMed2025

Leclercia barmai sp. nov., isolated from worm castings of Eisenia fetida, is a urease-positive, 3-nitropropionic acid and glycerol-consuming bacterium.

A comprehensive polyphasic characterization has validated the unique taxonomic position of a novel bacterium, strain EMC7T, isolated from the worm castings of earthworm, Eisenia fetida, collected from the Centre for Floriculture and Agri-Business Management (COFAM), NBU (26.7072° N, 88.3554° E). Whole-genome sequence of this Gram-stain-negative, facultatively anaerobic, motile, rod-shaped bacterium showed maximum sequence homology with Leclercia adecarboxylata NBRC 102595T, placing it within the genus Leclercia. The genome of EMC7T is 5.03 Mbp with a G + C content of 56.3 mol%. Phylogenetic analyses established its distinctiveness from Leclercia adecarboxylata and Leclercia tamurae. DNA-DNA hybridization (dDDH) value was 23.6%, and the average nucleotide identity (ANI) was 82.1%, both below the thresholds for prokaryotic species differentiation. Predominant fatty acids were C16:0 (29.53%), summed feature 3 (C16:1ω7c/C16:1ω6c, 16.51%), and C18:1ω7c (10.90%). Notably, EMC7T exhibited urease activity and could metabolize 3-nitropropionic acid (3-NPA), glycerol, tellurite, selenate, and selenite, suggesting potential bioremediation applications. Biochemical tests, phenotypic traits, genotypic data, and physiological properties cumulatively differentiated EMC7T from its closest relatives. Based on chemotaxonomic, phenotypic, genomic, and phylogenetic evidence, strain EMC7T represents a novel bacterial species of the genus Leclercia, for which the name Leclercia barmai sp. nov. (type strain EMC7T = MCC 5183T = JCM 36544T) is proposed.

Animals↗