Biology subjects

Berthold, D. L.

Publications and source records attributed to Berthold, D. L..

3 recordsLinked to original sources

bioRxiv2026

Metabolic cascades drive spatial prebiotic fermentation in a defined gut consortium

Dietary fiber deficiency shifts the gut microbiota to degrade host mucus, compromising intestinal homeostasis. Mechanistically linking in vitro metabolic dynamics of fiber degradation to in vivo outcomes remains challenging due to a lack of representative model systems. Introducing spatial mucin structures to a defined Oligo-Mouse-Microbiota (OMM12) in vitro consortium allowed us to recapitulate the spatio-temporal dynamics of xylooligosaccharide (XOS) processing in gnotobiotic mice. XOS supplementation rapidly established a stable community state in vitro and in vivo across compositional, metabolic and transcriptional levels. XOS supplementation established distinct functional guilds: Bifidobacterium animalis and Blautia coccoides partitioning xylose and arabinose catabolism, whilst profiting from XOS degradation by Bacteroides caecimuris. Along the colonic axis, a spatial XOS gradient exposes Bl. coccoides's substrate preference for xylose and drives longitudinal functional adaptations. Altogether, our predictive platform proves that regional microenvironments govern prebiotic efficacy, highlighting spatial cascades as essential parameters for targeted microbiome interventions.

microbiology↗

bioRxiv2026

Microbiota during early life windows orchestrates intestinal maturation and barrier formation in the offspring

There is a critical window in early life for immune development that prepares a young mammal for postnatal exposure to environmental, dietary and microbial antigens. Both the maternal microbiota and endogenous colonization have emerged as pivotal drivers in this process. Using gnotobiotic mouse models and reversible colonization to model the effects of the maternal microbiota during pregnancy compared with early life colonization on the small intestinal epithelium we show that both microbial metabolites originating from the maternal microbiota and the postnatal endogenous microbiota drive intestinal epithelial maturation by modulating epigenetic signatures. Microbiota-derived signals from both the pregnant mother and from endogenous postnatal colonisation drove the BLIMP1-guided epithelial neonatal-to-adult transition at weaning through epigenetic mechanisms and direct transcriptional effects. These microbial signals also shaped the developmental trajectory of barrier-forming tight junctional claudins in the neonatal intestine, increased aerobic respiration, and increased the gene expression of xenosensors. Thus, both maternal and endogenous microbiota derived drivers of the offspring's epigenetic and transcriptomic intestinal epithelial landscape fine-tuned the timing of epithelial maturation and augmented functional plasticity at weaning.

microbiology↗

bioRxiv2019

IRF5 promotes intestinal inflammation by guiding monocyte differentiation towards a pathogenic CD11c+ macrophage phenotype

Mononuclear phagocytes (MNPs) play a key role in maintaining intestinal homeostasis but also in triggering immunopathology in response to acute microbial stimulation, which induces the recruitment of masses of Ly6Chi monocytes to the gut. The regulators that control monocyte tissue adaptation in the gut remain poorly understood. Interferon Regulatory Factor 5 (IRF5) is a transcription factor previously shown to play a key role in maintaining the inflammatory phenotype of macrophages. Here we investigate the impact of IRF5 on the MNP system and physiology of the gut at homeostasis and during inflammation. We demonstrate that IRF5 deficiency has a limited impact on colon physiology at steady state, but ameliorates immunopathology during Helicobacter hepaticus induced colitis. Inhibition of IRF5 activity in MNPs phenocopies global IRF5 deficiency. Using a combination of bone marrow chimera and single cell RNA-sequencing approaches we compare the differentiation trajectories of wild type and IRF5 deficient monocytes in a shared inflammatory environment and demonstrate that IRF5 stipulates a choice in monocyte differentiation towards macrophages. Specifically, IRF5 promotes the generation of pathogenic CD11c+ macrophages and controls the production of inflammatory mediators by these cells. Thus, we identify IRF5 as a key transcriptional controller of pathogenic monocyte differentiation in the gut.

immunology↗