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Delaroque, C.

Publications and source records attributed to Delaroque, C..

3 recordsLinked to original sources

The chemorepellent effect of metformin limits bacterial penetration into mammalian mucus by altering bacterial motility

Metformin improves metabolic health and remodels the intestinal microbiota, yet how these microbial changes contribute to therapeutic benefits remains incompletely understood. We combined human metagenomics, quantitative analyses of bacterial behavior and ex vivo mucus models to investigate how metformin modulates host-microbiota interactions. Human metagenomics revealed metformin-associated enrichment of chemotaxis- and motility-related genes. At millimolar concentrations, metformin acted as a bacterial chemorepellent, an effect abolished by deletion of the chemotaxis regulator CheY and dependent on the chemoreceptor Tsr. Direct metformin exposure or fecal water from metformin-treated individuals reduced bacterial penetration into mucin, an effect reproduced in intestinal mucus from pigs fed a moderate-fat diet. Metformin treatment was further associated with reduced fecal flagellin activity and increased anti-flagellin IgA. Together, these findings identify bacterial chemotaxis as a target of metformin and reveal a mechanism by which metformin may limit bacterial access to the intestinal mucus barrier.

microbiology↗

A prebiotic-postbiotic combination supports dietary carbohydrate-targeting functional properties in a fiber-deprived microbiota

Dietary fiber deprivation compromises gut mucosal barrier integrity by promoting microbial degradation of host mucus, a process linked to various gut-related auto immune diseases. While postbiotics are considered safer alternatives to fiber for susceptible patients, their mechanistic ef- fects on a fiber-deprived gut remain poorly understood. Here, we demonstrate in a mouse model that a fermented postbiotic, alone or in combination with a prebiotic and aloe vera, counteracted the increase of detrimental properties of the microbiota on a fiber-free diet. The supplement regimen reshaped the gut microbiota, counteracting the expansion of key mucin-degrading bac- teria, including Akkermansia muciniphila and Parabacteroides goldsteinii. Metatranscriptomic analysis revealed this compositional change corresponded to a community-wide functional pivot away from expressing mucinolytic enzymes, such as sialidases, and towards utilizing alternative substrates. These microbial shifts recapitulated the effects of dietary fiber reintroduction and translated to direct host benefits, including sustentation of the colonic mucus layer and attenu- ation of diet-induced type III immune cytokine expression. Our findings provide a mechanistic rationale for using postbiotics to functionally replace dietary fiber, offering a promising strategy to support gut homeostasis in contexts where fiber intake is limited.

microbiology↗

Maternal diet alters offspring early life host-microbiota communication through goblet cells, resulting in long-lasting diseases susceptibility

A crucial early-life developmental phase regulates microbiome settling while establishing critical and long-lasting immune and metabolic processes. During this period, the influence of select components of maternal diet on offspring microbiota and health remains largely unknown. To investigate the potential transgenerational impact of maternal exposure to microbiota-disrupting factors, dams were subjected prior breeding to dietary emulsifiers, known to directly perturb the microbiota. Such maternal exposure induced early-life microbiota alterations in offspring which associated with long-lasting susceptibility to diet-induced obesity and intestinal inflammation. These detrimental effects were entirely prevented by early-life microbiota normalization through cross-fostering procedures. Mechanistically, maternal emulsifier exposure induces strong offsprings impairment in goblet cells-mediated host-microbiota communication which is central in driving the observed long-lasting deleterious effects. To conclude, this study underscores the central role played by maternal intake of microbiota-disrupting agents on the next generations microbiota, with long lasting consequences for intestinal and metabolic health.

microbiology↗