Biology subjects

Rolhion, N.

Publications and source records attributed to Rolhion, N..

5 recordsLinked to original sources

bioRxiv2026

Decoding E. coli's Gut Survival Strategies: A CRISPRi Approach Across Diets, Inflammatory Environment and Strains

Escherichia coli, a ubiquitous member of the mammalian gut microbiota, exhibits remarkable genetic diversity underpinning its commensal or pathogenic lifestyles. Deciphering the precise genetic determinants enabling E. colis adaptation within the complex and dynamic intestinal environment is critical for understanding host-microbe symbiosis and enteric disease pathogenesis. Here, we establish an in vivo CRISPR interference (CRISPRi) platform that leverages bacterial gene fitness profiles as a high-resolution functional reporter to define the molecular niche and selective forces encountered by E. coli within mice harboring a defined minimal microbial community (OligoMM12). Our investigation revealed that dietary regimens profoundly reshape E. colis metabolic landscape and that the profile of essential genes help identify cross-feeding interactions. Comparative screens across a laboratory strain (MG1655), a Uropathogenic, and Adherent-Invasive E. coli (AIEC), identify distinct genetic requirements for intestinal colonization, highlighting divergent motility, stress response, and respiration strategies. In a host inflammatory environment, we find that the AIEC strain LF82 alters its colonization pattern, shifting towards the small intestine, and adapts to the inflammatory environment by remodeling its metabolism and stress responses. Notably, we uncover a critical role for mobile genetic elements, with the observation that inflammation triggers the induction of the Gally prophage which is beneficial for fitness in the healthy gut but becomes detrimental during inflammation. These findings provide a high-resolution genetic atlas of E. colis functional adaptation and demonstrate the utility of functional genomics to probe the gut environment itself.

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↗

bioRxiv2022

Human CD4+/CD8α+ regulatory T cells induced by Faecalibacterium prausnitzii protect against intestinal inflammation

Faecalibacterium prausnitzii (F. prausnitzii), a dominant bacterium of the human microbiota, is decreased in patients with inflammatory bowel diseases (IBD) and exhibits anti-inflammatory effects. In human, colonic lamina propria contains IL-10-positive, Foxp3-negative regulatory T cells (Treg) characterized by a double expression of CD4 and CD8 (DP8) and a specificity for F. prausnitzii. This Treg subset is decreased in IBD. The in vivo effect of DP8 cells has not been evaluated yet. Here, using a humanized model of NOD.Prkcscid IL2r{gamma}-/- (NSG) immunodeficient mouse strain that expresses human leucocyte antigen D-related 4 (HLA-DR4) but not murine class II (NSG-Ab{degrees} DR4), we demonstrated a protective effect of DP8 Tregs combined with F. prausnitzii administration in a colitis model. In a cohort of patients with IBD, we showed an independent association between the frequency of circulating DP8 cells and disease activity. Finally, we pointed out a positive correlation between F. prausnitzii-specific DP8 Tregs and the amount of F. prausnitzii in fecal microbiota in healthy individuals and patients with ileal Crohns disease.

immunology↗

bioRxiv2022

CARD9 in Neutrophils Protects from Colitis and Controls Mitochondrial Metabolism and Cell Survival

ObjectivesInflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown. DesignWe used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real time bioenergetic profile analysis (Seahorse). ResultsLymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+ cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction in neutrophils leads to their premature death through apoptosis, especially in oxidative environment. The decrease of fonctional neutrophils in tissues could explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. ConclusionThese results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils. Summary boxO_LIWhat is already known about this subject? O_LIInflammatory bowel disease (IBD) results from genetic predisposition, microbiota dysbiosis and environmental factors, but the alterations of the immune response leading to chronic intestinal inflammation are still not fully understood. C_LIO_LICaspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. C_LIO_LIHowever, the cell types and cellular mechanisms involved in the CARD9 protective role against inflammation remain unknown. C_LI C_LIO_LIWhat are the new findings? O_LICARD9 expression in neutrophils, but not in lymphocytes, epithelial cells or CD11c+ cells, protects against DSS-induced colitis. C_LIO_LIIn the absence of CARD9, mitochondrial dysfunction in neutrophils leads to their premature death through apoptosis, especially in oxidative environment. C_LIO_LIThe decrease of fonctional neutrophils in tissues could explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. C_LI C_LIO_LIHow might it impact on clinical practice in the foreseeable future? O_LIThese results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation. C_LIO_LIUnderstanding the role of neutrophils in chronic inflammation could lead to innovative therapeutic strategies targeting these key immune cells for various complex diseases. C_LI C_LI

immunology↗

bioRxiv2019

Specific targeting of intestinal Prevotella copri by a Listeria monocytogenes bacteriocin

Deciphering the specific function of every microorganism in microbial gut communities is a key issue to interrogate their role during infection. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, that specifically targets the abundant gut commensal Prevotella copri and affects Listeria infection. Oral infection of conventional mice with a {Delta}lmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria, while no difference is observed in germ-free mice. This microbiota-dependent effect is phenocopied by precolonization of germ-free mice before Listeria infection, with P. copri, but not with other commensals. Together, these data unveil a role for Prevotella in controlling intestinal infection, highlighting that pathogens may selectively deplete microbiota to avoid excessive inflammation.

microbiology↗