Benoit Chassaing | PubMed Health

PubMed2026

In vivo CRISPRi screens reveal Escherichia coli functional adaptations in the mouse gut.

Escherichia coli exhibits remarkable genetic diversity that enables it to adapt to the intestinal environment. Here we establish an in vivo CRISPR interference platform that leverages bacterial gene fitness as a high-resolution functional reporter of E. coli adaptations within mice harbouring a defined minimal microbial community (OligoMM12). The screen revealed that diet profoundly shapes the metabolic landscape of E. coli and the essential gene profile identified cross-feeding interactions. Comparison between a laboratory strain (MG1655), a uropathogenic strain (CFT073) and an adherent-invasive E. coli (AIEC LF82) identified distinct genetic requirements for intestinal colonization, highlighting divergent motility, stress response and respiration strategies. In a host inflammatory environment, we found that AIEC LF82 preferably colonized the small intestine with a mobile genetic element, Gally prophage, playing an important role in modulating fitness. These findings provide a high-resolution genetic atlas of E. coli's functional adaptation and demonstrate the utility of functional genomics to probe the gut environment itself.

Journal Article↗

PubMed2026

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗