Biology subjects

Tilg, H.

Publications and source records attributed to Tilg, H..

3 recordsLinked to original sources

bioRxiv2025

Escherichia-Shigella expansion and metabolite dysregulation in type 3c diabetes

Emerging evidence supports a bidirectional gut-pancreas axis in which microbial dysbiosis, barrier dysfunction, and altered metabolite fluxes contribute to pancreatogenic diabetes (T3cDM). Whether gut microbial changes reflect systemic metabolic disturbances or primarily arise from exocrine pancreatic insufficiency (EPI) remains unclear. We profiled the gut microbiome of 48 outpatients with T3cDM, type 1 diabetes (T1DM), and healthy controls. Genus-level 16S rRNA data were analysed using cross-validated LASSO logistic regression and patient-specific community metabolic models. T3cDM showed reduced -diversity and distinct {beta}-diversity compared with T1DM and controls. Key compositional shifts included enrichment of Enterobacteriaceae (notably Escherichia-Shigella) and Streptococcaceae in T3cDM. LASSO models discriminated T3cDM from T1DM (AUC 0.867; accuracy 0.818), highlighting Blautia, Escherichia-Shigella, Streptococcus, Clostridium, and Faecalibacterium as predictors. Metabolic modelling indicated elevated Escherichia-Shigella growth in T3cDM and disease-specific metabolite fluxes. Gut microbial shifts in T3cDM predominantly reflect EPI rather than systemic metabolic disturbances characteristic of T1DM, underscoring the central role of exocrine pancreatic dysfunction in shaping the gut microbiome and its metabolic activity.

microbiology↗

bioRxiv2021

Interleukin-11 plays a key role in human and mouse alcohol-related liver disease

BackgroundAlcoholic hepatitis (AH) reflects acute exacerbation of alcoholic liver disease (ALD) and is a growing healthcare burden worldwide with limited treatment options. Interleukin-11 (IL-11) is a pro-fibrotic, pro-inflammatory cytokine with increasingly recognized toxicities in parenchymal and epithelial cells. AimThe aim of this study was to explore the prognostic value of IL-11 serum levels in patients suffering from AH and cirrhosis of various etiology and to understand the role of IL-11 in experimental ALD. MethodsIL-11 serum concentration and tissue expression was determined in a cohort comprising 50 patients with AH, 110 patients with cirrhosis and 19 healthy volunteers. Findings were replicated in an independent patient cohort including 186 patients. Ethanol-fed wildtype mice were treated with a neutralizing murine IL-11 receptor-antibody (anit-IL11RA) and thereafter examined for severity signs and markers of ALD. ResultsHuman IL-11 serum concentration and liver tissue expression increased with severity of liver disease and were most pronounced in AH. In a multivariate Cox-regression, a serum level above 6.4 picograms/milliliter was a MELD independent risk factor for transplant-free liver disease survival in patients with compensated and decompensated cirrhosis. Findings were confirmed in an independent cohort. In mice, severity of alcohol-induced liver inflammation was positively correlated to enhanced hepatic IL-11 expression. Pretreatment with a neutralizing anti-IL11RA inhibited hepatic inflammation and mice were protected from ethanol-induced liver injury. In comparison to IgG-control, ethanol-fed mice treated with anti-IL11RA showed decreased steatosis, hepatic neutrophil infiltration, and expression of pro-inflammatory cytokines. ConclusionIL-11 plays a crucial role in the pathogenesis of ALD and could serve as an independent prognostic factor for transplant-free survival. Blocking IL-11 signaling might be a therapeutic option in human ALD, particularly AH.

immunology↗

bioRxiv2020

Human liver microbiota modeling strategy at the early onset of fibrosis

To understand the pathophysiological impact of liver microbiota on the early stages of fibrosis we identified the corresponding microbiota sequences and overcome the impact of different group size and patient origins with adapted statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2) were collected from Romania(n=36), Austria(n=10), Italy(n=19), and Spain(n=17). The 16SrDNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50 % of liver taxa were Enterobacteriaceae and Pseudomonadaceae. The Caulobacteraceae, Flavobacteriaceae and Propionibacteriaceae discriminated between F0 and F1. The preQ0 biosynthesis and pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. Altogether, our results suggest a role of bacterial translocation to the liver in the progression of fibrosis. This statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses.

pathology↗