Biology subjects

Cuiv, P. O.

Publications and source records attributed to Cuiv, P. O..

4 recordsLinked to original sources

bioRxiv2026

Microbial Immunomodulatory Function is Altered in Inflammatory Bowel Disease Independent of Microbial Composition

Inflammatory bowel diseases (IBD) are chronic and relapsing immune-mediated conditions in which the NF-{kappa}B and STAT3 signalling pathways play central roles in pathogenesis. While gut microbiome dysbiosis is well described in IBD, its functional consequences, particularly microbial immunomodulatory function (MIF) remain poorly defined. Here, we integrated functional assays with metagenomic profiling to characterise microbiome-driven immune modulation in IBD. Faecal water from non-IBD controls and IBD patients was assessed using NF-{kappa}B and STAT3 reporter systems, alongside high-throughput screening of 2,820 bacterial isolates (94 per subject). Despite minimal differences in overall microbial composition, faecal water from patients with ulcerative colitis (UC) and Crohns disease (CD) significantly increased NF-{kappa}B activity under both basal and TNF-stimulated conditions. Non-IBD controls harboured a higher proportion of suppressive bacterial isolates (21.52%) compared to UC (5.64%) and CD (2.45%), whereas activating isolates were enriched in IBD (UC: 34.47%; CD: 39.36% vs. non-IBD: 5.35%). Similar trends were observed for IL-23-mediated STAT3 activation. Integration of metagenomic and pathway-level analyses identified 24 KEGG pathways associated with inflammatory signalling and faecal lipocalin-2, as well as amino acid, carbohydrate, lipid, cofactor, and nucleotide metabolism. These findings demonstrate that the IBD microbiome is functionally reprogrammed toward pro-inflammatory activity, independent of compositional changes. Defining patient-specific MIF profiles may provide a framework for precision microbiome-based therapeutic strategies in IBD.

microbiology↗

bioRxiv2026

Bioactive produced by Enterococcus Faecalis targets IL-23 signalling and protects against colitis and joint disease

The IL-23/Th17 axis is a central driver of intestinal and spondyloarthritic inflammation, yet upstream regulatory mechanisms linking microbial signals to IL-23 production remain incompletely defined. NF-{kappa}B signalling, particularly via the c-Rel subunit, is a critical transcriptional regulator of IL23A (p19), positioning c-Rel as a nodal checkpoint in mucosal inflammation. Here, we demonstrate that cell-free supernatant derived from Enterococcus faecalis AHG0090 (AHG0090-CS) suppresses c-Rel-dependent IL-23 signalling and attenuates inflammatory pathology across murine models of gut and joint disease. In the ZAP-70 mutant SKG model of spondyloarthritis and ileitis, AHG0090-CS significantly reduced weight loss, joint scores, and histological gut inflammation following curdlan challenge. In the Winnie model of spontaneous colitis, treatment similarly diminished inflammatory cytokine production. Mechanistically, AHG0090-CS reduced IL-23p19 mRNA and protein expression in intestinal tissue and lamina propria myeloid cells, accompanied by decreased nuclear c-Rel intensity. Suppression extended to downstream IL-23-associated cytokines including IL-17A, GM- CSF, MCP-1 and IL-6. In human peripheral blood mononuclear cells and macrophages, AHG0090-CS attenuated LPS-induced IL-23 and pro-inflammatory cytokine production, supporting translational relevance. Collectively, these findings identify microbial modulation of c-Rel-dependent IL-23 signalling as a tractable mechanism to restrain gut-joint inflammation and highlight targeting upstream NF-{kappa}B pathways as a therapeutic strategy in IL-23-driven immune-mediated disease.

microbiology↗

bioRxiv2024

A maternal high-fat diet predisposes to infant lung disease via increased neutrophil-mediated IL-6 trans-signaling

Poor maternal diet during pregnancy predisposes to severe lower respiratory tract infections (sLRI) in infancy, which in turn, increases childhood asthma risk, however the underlying mechanisms remain poorly understood. Here, we show that the offspring of high fat diet (HFD)-fed mothers ( HFD-reared pups) developed a sLRI following pneumovirus inoculation in early-life and subsequent asthma in later-life upon allergen exposure. Prior to infection, HFD-reared pups developed microbial dysbiosis and low-grade systemic inflammation (LGSI), characterized by hyper-granulopoiesis in the liver and elevated inflammatory cytokine expression, most notably IL-17A, IL-6 and sIL-6R (indicative of IL-6 trans-signaling) in the circulation and multiple organs, but most prominently the liver. Inhibition of IL-6 trans-signaling, using sgp130Fc transgenic mice or via specific genetic deletion of IL-6Ra on neutrophils, conferred protection against both diseases. Taken together, our findings suggest that a maternal HFD induces neonatal LGSI that predisposes to sLRI and subsequent asthma via neutrophil-mediated IL-6 trans-signaling.

immunology↗

bioRxiv2019

Secreted microbial metabolites modulate gut immunity and inflammatory tone

Evidence is emerging that microbiome-immune system crosstalk regulates the tenor of host intestinal immunity and predisposition to inflammatory bowel disease (IBD). We identified five NF-{kappa}B suppressive strains affiliated with Clostridium clusters IV, XIVa and XV that independently suppressed secretion of the chemokine IL-8 by peripheral blood mononuclear cells and gut epithelial organoids from healthy human subjects, as well as patients with the predominant IBD subtypes, Crohns disease and ulcerative colitis. The NF-{kappa}B suppressive Clostridium bolteae AHG0001, but not C. bolteae BAA-613, suppressed cytokine-driven inflammatory responses and endoplasmic reticulum stress in gut epithelial organoids derived from Winnie mice that develop spontaneous colitis. This predicted in vivo responses thereby validating a precision medicine approach to treat Winnie colitis and suggesting the microbiome may function as an extrinsic regulator of host immunity. Finally, we identified a novel molecule associated with NF-{kappa}B suppression indicating gut bacteria could be harnessed to develop new therapeutics.

microbiology↗