Characterization of an NADPH-dependent 17β-hydroxysteroid dehydrogenase from a urinary tract bacterial isolate

The Journal of Steroid Biochemistry and Molecular Biology · 2026-03-15

Neutralization of Microbiota-Derived Corisin Shows Early Amelioration of Advanced Pulmonary Fibrosis

Advances in respiratory medicine · 2026-02-06

BACKGROUND: Corisin, a microbiota-derived proapoptotic peptide, has emerged as a key mediator of epithelial injury, inflammation, and acute exacerbation in fibrotic lung disease. Although acute corisin inhibition prevents exacerbations in experimental models, its therapeutic impact on established pulmonary fibrosis remains unclear. This study evaluated the short-term efficacy of corisin neutralization in advanced transforming growth factor-β1 (TGF-β1)-driven lung fibrosis. METHODS: Male TGF-β1 transgenic mice with established fibrosis were allocated to computed tomography-matched groups and treated intraperitoneally with an anti-corisin monoclonal antibody (clone 21A) or control IgG every two days for one week. Bronchoalveolar lavage fluid (BALF) analysis, histopathology, assessment of apoptosis, Ashcroft scoring, and lung hydroxyproline quantification were performed on day 8. RESULTS: Anti-corisin treatment significantly reduced BALF inflammatory cell counts, including macrophages and lymphocytes. Histological analyses demonstrated decreased alveolar epithelial apoptosis, reduced collagen deposition, and significantly lower Ashcroft fibrosis scores. Lung hydroxyproline content was also markedly decreased, indicating attenuation of extracellular matrix accumulation. CONCLUSIONS: Short-term neutralization of microbiota-derived corisin rapidly alleviates inflammation, epithelial injury, and fibrotic remodeling in advanced TGF-β1-induced pulmonary fibrosis. These findings identify corisin as an upstream driver of ongoing fibrogenesis and support its potential as a therapeutic target in progressive fibrotic lung disease.

Anaerobic Fungal Carbohydrate-Binding Modules Exhibit Preference for Fusion to Hemicellulases and Enhance Their Enzymatic Hydrolysis

Journal of Agricultural and Food Chemistry · 2026-01-26

As auxiliary components of the carbohydrate active enzymes (CAZymes), carbohydrate-binding modules (CBMs) influence the enzymatic hydrolysis of substrates. To investigate the role of anaerobic fungal CBMs in lignocellulose degradation, an architectural analysis of bacterial and fungal CBM-containing protein sequences was completed. Results indicated that 67.9% of the fungal CBMs were incorporated into the plant-biomass-degrading enzymes and 51.1% of the anaerobic fungal CBMs were biased to be fused with the hemicellulose-degrading enzymes. Based on the transcriptomic data of anaerobic fungus Pecoramyces ruminantium F1, three upregulated CBM-fused hemicellulose-degrading enzyme gene clusters were identified. Results suggested that the fused CBMs retained the enzymatic function of the associated CAZymes. Importantly, the CBM1 domains of acetyl xylan esterase (AxeA16138) and α-L-arabinofuranosidase (AraA02173) possessed a crucial role to promote the xylanase-mediated hydrolysis of hemicellulose. These results demonstrated that anaerobic fungal CBMs harbor substantial potential to enhance hemicellulose degradation.

<i>Bacteroides intestinalis</i> -Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-29

Summary Insufficient dietary fiber intake is strongly associated with gut microbiome dysfunction and an increased risk of noncommunicable diseases. Synergistic synbiotics, which pair defined microbial strains with their preferred carbohydrate substrates, offer a promising strategy to restore these functions. However, the rational design of such interventions remains challenging because of insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal Bacteroides intestinalis ( B . intestinalis ) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between B . intestinalis and its substrate, insoluble wheat arabinoxylan abundant in dietary fiber (inWAX), enhances the production of anti-diabetic and anti-steatotic bile acid species, anti-inflammatory and antioxidant phenolic compounds, and a spectrum of neuroactive compounds. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen implicating pathways governing circadian rhythm regulation, lipid metabolism, and immune defense. Importantly, these beneficial effects are preserved in conventionally raised mice with established high-fat diet-induced obesity, where B . intestinalis and inWAX improve glucose tolerance. Our findings uncover a mechanistic framework linking B . intestinalis -mediated fiber fermentation to gut-metabolism-immune crosstalk and establish a rational foundation for precision synbiotic design.

Exploratory Evaluation of Circulating Microbiota-Derived Corisin Levels in Women with Adverse Pregnancy Outcomes

Antioxidants · 2025-05-31

Preterm birth and low birth weight remain major contributors to neonatal morbidity and mortality, yet the underlying mechanisms are not fully understood. Maternal microbiota has been implicated in adverse pregnancy outcomes, but key mediators remain unidentified. We previously showed that the microbiota-derived peptide corisin induces epithelial apoptosis via mitochondrial membrane depolarization and reactive oxygen species accumulation. In this retrospective preliminary study, we evaluated the association between maternal serum corisin levels and pregnancy outcomes in 84 eligible women. Among them, 10 experienced preterm birth, and 22 delivered low-birth-weight infants. Corisin levels were significantly elevated in these groups compared with women with full-term, normal-weight deliveries. Preterm birth was associated with increased tissue factor, while low birth weight correlated with higher thrombin-antithrombin complex and soluble thrombomodulin and lower fibrinogen levels. Corisin concentrations showed negative correlations with maternal BMI, birth weight and length, and estimated fetal weight. Positive correlations were observed between corisin, myeloperoxidase, and several coagulation markers. These preliminary findings suggest that elevated maternal corisin levels are associated with adverse pregnancy outcomes and may reflect underlying mechanisms involving oxidative stress and coagulation activation. Further investigation is warranted to clarify its potential role as a microbiota-derived biomarker in pregnancy complications.

An expanded metabolic pathway for androgen production by commensal bacteria

Nature Microbiology · 2025-04-21 · 30 citations

Complete genome sequence of <i>Methylocystis echinoides</i> strain RIM isolated from soil

Microbiology Resource Announcements · 2025-02-25

ABSTRACT We report here the complete genome sequence of a type II methanotrophic bacterium, Methylocystis echinoides strain RIM, isolated from the soil surface at Urbana, Illinois. This genome was obtained via HiFi PacBio Sequel II sequencing.

A widespread hydrogenase supports fermentative growth of gut bacteria in healthy people

Nature Microbiology · 2025-10-23 · 3 citations

Abstract Disruption of hydrogen (H 2 ) cycling in the gut is linked to gastrointestinal disorders, infections and cancers. However, the mechanisms and microorganisms controlling H 2 production in the gut remain unresolved. Here we show that gut H 2 production is primarily driven by the microbial group B [FeFe]-hydrogenase. Metagenomics and metatranscriptomics of stool and tissue biopsy samples show that hydrogenase-encoding genes are widely present and transcribed in gut bacteria. Assessment of 19 taxonomically diverse gut isolates revealed that the group B [FeFe]-hydrogenases produce large amounts of H 2 gas and support fermentative growth of Bacteroidetes and Firmicutes. Further biochemical and spectroscopic characterization of purified enzymes show that they are catalytically active, bind a di-iron active site and reoxidize ferredoxin derived from the pyruvate:ferredoxin oxidoreductase reaction. Group B hydrogenase-encoding genes are significantly depleted in favour of other fermentative hydrogenases in patients with Crohn’s disease. Finally, metabolically flexible respiratory bacteria may be the dominant hydrogenotrophs in the gut, rather than acetogens, methanogens and sulfate reducers. These results uncover the enzymes and microorganisms controlling H 2 cycling in the healthy human gut.

Characterization of an NADPH-dependent 17β-hydroxysteroid dehydrogenase from a urinary tract bacterial isolate

SSRN Electronic Journal · 2025-01-01

Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging

Nature Communications · 2025-08-25 · 2 citations

The increasing global prevalence of diabetic nephropathy poses substantial health and economic burdens. Currently, effective anti-fibrotic therapies for managing kidney fibrosis associated with chronic kidney disease are lacking. This study reveals corisin, a microbiota-derived peptide, as a central driver in the progression of diabetic kidney fibrosis. Corisin levels were found to be markedly elevated in the serum of diabetic chronic kidney disease patients relative to healthy controls, with strong correlations to advanced disease stages and declining renal function. In a murine model of kidney fibrosis, corisin levels were similarly heightened, directly contributing to increased inflammation and worsening fibrosis and renal impairment. Notably, the use of a monoclonal anti-corisin antibody significantly reduced nephropathy severity in diabetic mice. Through molecular dynamics simulations and experimental validation, we demonstrated that corisin interacts with human serum albumin, potentially enhancing its renal accumulation and pathological impact. The pathogenic mechanism of corisin involves the acceleration of cellular senescence and the induction of epithelial-mesenchymal transition and apoptosis in kidney cells. These findings underscore the critical role of corisin in progressive diabetic nephropathy and suggest a promising new target for therapeutic intervention.