Biology subjects

Tremaroli, V.

Publications and source records attributed to Tremaroli, V..

3 recordsLinked to original sources

bioRxiv2025

Characterization and description of Clostridium filamentum ETTB, a novel gut bacterium with TLR5 modulating properties

The Clostridium genus is highly heterogeneous, encompassing numerous species and strains, many of which remain to be isolated and characterized to better understand their relationship to host physiology. This study aimed to isolate and characterize novel bacterial species within the Clostridium genus and explore their potential links to host health. Under microaerophilic conditions, we isolated and characterized three bacterial isolates belonging to a new anaerobic Clostridium species, designating Clostridium sp. DSM 115107 (Clostridium filamentum ETTB3) as the type strain. C. filamentum ETTB isolates are rod- to filament-shaped, Gram-positive bacteria and exhibit poor growth when cultured on rich media such as LYBHI. Genome sequencing and phylogenetic analysis revealed that C. filamentum ETTB belongs to the Clostridium genus and clusters closely with Clostridium saudiense JCC. Interestingly, C. filamentum ETTB has a significantly smaller genome compared to C. saudiense JCC containing a reduced repertoire of genes involved in carbohydrate degradation and amino acid synthesis and a larger number of genes related to cell motility, including an additional copy of the fliC gene. Unlike C. saudiense, C. filamentum ETTB adopted a filamentous morphology when in contact with Caco-2 cells and stimulate the TLR5 pathway in Caco-2 cells. Metagenomics analysis revealed that C. filamentum ETTB is present in both industrialized and non-industrialized populations, although the relative abundance varying considerably between and within individuals. Our study identifies a novel bacterial strain adapted for the human gut that has the potential to influence host immune response by activating TLR5 pathway.

microbiology↗

bioRxiv2022

Systems analysis of metabolic responses to a mixed meal test in an obese cohort reveals links between tissue metabolism and the gut microbiota

Individuals with prediabetes and type 2 diabetes mellitus (T2DM) have poor ability to adapt to diet-triggered perturbations. We investigated global metabolic responses to a mixed meal test (MMT) in morbidly obese individuals with different diabetic status by performing plasma metabolomic profiling. Abnormal metabolism of carbohydrates, (branched-chain) amino acids, fatty acids and acylcholines in individuals with (pre)diabetes was observed. Moreover, differences in metabolic responses were associated with altered fecal metagenomics and transcriptomes of liver, jejunum and adipose tissues, which revealed a modified gut microbiome and multi-tissue metabolism in individuals having insulin resistance. Finally, using integrative machine learning models, we built a predictive model based on metabolomics data after 2h MMT, and identified possible new biomarkers for glycemic control including N-acetylaspartate and phenylalanine-derived metabolites that may be useful for diagnosis, intervention and prevention of T2DM.

systems biology↗

bioRxiv2020

Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis

Hexokinases (HK) catalyze the first step of glycolysis and thereby limit its pace. HK2 is highly expressed in the gut epithelium, plays a role in immune responses and is upregulated in inflammation and ulcerative colitis 1-3. Here, we examined the microbial regulation of HK2 and its impact on intestinal inflammation by generating mice lacking HK2 specifically in intestinal epithelial cells (Hk2{Delta}IEC). Hk2{Delta}IEC mice were less susceptible to acute intestinal inflammation upon challenge with dextran sodium sulfate (DSS). Analyzing the epithelial transcriptome from Hk2{Delta}IEC mice during acute colitis revealed downregulation of cell death signaling and mitochondrial dysfunction dependent on loss of HK2. Using intestinal organoids derived from Hk2{Delta}IEC mice and Caco-2 cells lacking HK2, we identified peptidyl-prolyl cis-trans isomerase (PPIF) as a key target of HK2-mediated regulation of mitochondrial permeability and repression of cell-death during intestinal inflammation. The microbiota strongly regulated HK2 expression and activity. The microbially-derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression and oral supplementation protected wildtype but not Hk2{Delta}IEC mice from DSS colitis. Our findings define a novel mechanism how butyrate may act as a protective factor for intestinal barrier homeostasis and suggest targeted HK2 inhibition as a promising therapeutic avenue in intestinal inflammation.

immunology↗