Biology subjects

Seksik, P.

Publications and source records attributed to Seksik, P..

4 recordsLinked to original sources

bioRxiv2026

Type 6 secretion systems of adherent-invasive Escherichia coli isolated from Crohn's disease patients shape intestinal microbiota.

Adherent Invasive Escherichia coli (AIEC) colonize the ileal mucosa of Crohn's disease patients. Among bacterial virulence factors potentially implicated, type 6 secretion systems (T6SS) are molecular machineries sending effectors in prokaryotic or eukaryotic target cells. Two T6SS have been reported in AIEC LF82 reference strain. Here, we show that T6SS genes are more prevalent in Crohn's disease patients' microbiota compared to healthy controls, and that T6SS are more frequent in AIEC pathovar compared to E. coli in general and associated with FimH pathoadaptive polymorphism. The use of an in vitro gastrointestinal system coupled with T6SS promoter reporter assay highlighted expression of LF82 T6SS under gastrointestinal conditions, with a major role for bile salts. In mice infected with AIEC LF82 versus T6SS-deleted mutants, T6SS showed a functional impact in modulating the composition of mucosa-associated gut microbiota. Thus, AIEC may use their T6SS to compete with endogenous microbiota to colonize host mucosa.

microbiology↗

bioRxiv2025

Inhibition of IL-22-producing cells by Sutterella sp. bacteria

The gut microbiota constitutes a complex ecosystem essential for host defense against infection and maturation of the immune system. Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohns disease, are characterized by a severe inflammation of the intestine, arising from dysregulated control of host-microbiota crosstalk. However, neither the genetic bases of IBD nor the immune responses involved are fully understood. The pathobionts are currently under investigation for their active role in the development and the severity of IBD. These bacteria are present in the microbiota of healthy individuals without causing disease but have pathogenic potential when the intestinal environment is disturbed. Here, we highlighted Sutterella sp. as a new commensal pathobiont for its capacity to modulate the host immune functions. This anaerobic Gram-negative bacterium inhibits IL-22 production and AhR activity in mice and humans. The effectors responsible for the biological activity are large (>30 kDa) protein-based compounds secreted by Sutterella sp. These data enhance our understanding of the mechanisms that regulate host immune functions and pave the way for new therapeutic strategies to control gut inflammation.

immunology↗

bioRxiv2019

Partial loss of colonic primary cilia promotes inflammation and carcinogenesis

Primary cilia (PC) are important signaling hubs in cells and their deregulation has been associated with various diseases including cancer. Here we explored the role of PC in colorectal cancer (CRC) and colitis. In the colon we found PC to be mostly present on different subtypes of fibroblasts. Colons of mice exposed to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced colitis had decreased numbers of PC. We employed conditional knock-out strains for the PC essential genes, Kif3A and Ift88, to generate mice with reduced numbers of PC on colonic fibroblasts. These mice showed an increased susceptibility in the CAC model as well as in DSS-induced colitis. Colons from DSS-treated mice with PC-deficiency on fibroblasts displayed an elevated production of the pro-inflammatory cytokine IL-6 and colonic epithelial cells had diminished levels of HES-1, a key transcription factor of Notch signaling. Notably, an analysis of PC presence on biopsies of patients with ulcerative colitis as well as CRC patients revealed decreased numbers of PC on colonic fibroblasts in pathological versus surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/871772v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1f8eccdorg.highwire.dtl.DTLVardef@1829b3borg.highwire.dtl.DTLVardef@19d632aorg.highwire.dtl.DTLVardef@1d9833b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2018

Clinical data specification and coding for cross-analyses with omics data in autoimmune disease trials

ObjectivesAutoimmune and inflammatory diseases (AIDs) form a continuum of autoimmune and inflammatory diseases, yet AIDs nosology is based on syndromic classification. The TRANSIMMUNOM trial (NCT02466217) was designed to re-evaluate AIDs nosology through clinic-biological and multi-omics investigations of patients with one of 19 selected AIDs. To allow cross-analyses of clinic-biological data together with omics data, we needed to integrate clinical data in a harmonized database.\n\nMaterials and MethodsWe assembled a clinical expert consortium (CEC) to select relevant clinic-biological features to be collected for all patients and a cohort management team comprising biologists, clinicians and computer scientists to design an electronic case report form (eCRF). The eCRF design and implementation has been done on OpenClinica, an open-source CFR-part 11 compliant electronic data capture system.\n\nResultsThe CEC selected 865 clinical and biological parameters. The CMT selected coded the items using CDISC standards into 5835 coded values organized in 28 structured eCRFs. Examples of such coding are check boxes for clinical investigation, numerical values with units, disease scores as a result of an automated calculations, and coding of possible treatment formulas, doses and dosage regimens per disease.\n\nDiscussion21 CRFs were designed using OpenClinica v3.14 capturing the 5835 coded values per patients. Technical adjustment have been implemented to allow data entry and extraction of this amount of data, rarely achieved in classical eCRFs designs.\n\nConclusionsA multidisciplinary endeavour offers complete and harmonized CRFs for AID clinical investigations that are used in TRANSIMMUNOM and will benefit translational research team.

clinical trials↗