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S. Gschwendtner

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Open access Jul 2026

Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE

The relevance of high-sensitivity C-reactive protein (hsCRP), a marker of low-grade systemic inflammation, remains unclear with regard to its association with severity and clinical outcomes in wheeze/asthma. We aimed to assess the role of hsCRP across different phenotypes and severity levels. We studied children with preschool wheeze (≥ 2 episodes), and patients with GINA-defined asthma (school-age/adult) compared with healthy controls (HCs) in the well-characterized ALLIANCE (All Age Asthma Cohort) study. HsCRP was measured (AU5800®-CRP-Latex test) in 944 study participants (pediatric: n = 728; adult: n = 216) at baseline. Age-stratified analyses (age groups 0–5, 6–18, ≥ 18 years) of standardized log10-transformed hsCRP concentrations (age, sex, BMI, site) were performed using univariable tests and regression models. The validated ASSESS score and its dimensions (exacerbations, lung function, inhaled corticosteroids, symptom control) were primary outcomes. Adult patients with asthma showed higher hsCRP than HCs (OR 2.22, 95% CI 1.56–3.24). Across all ages, hsCRP increased with clinical severity of wheeze/asthma. The ASSESS score correlated positively with hsCRP in patients aged ≥ 6 years (R = 0.19, p = 0.007). hsCRP was increased in school-age asthmatics with prior exacerbations (OR 1.37, 95% CI 1.01–1.87), and in adult asthmatics with impaired lung function (R = 0.2, p = 0.013). Inhaled corticosteroid use was associated with lower hsCRP in preschool wheezers (OR 0.66, 95% CI 0.50–0.85) but higher levels in adults (OR 1.99, 95% CI 1.02–4.09). HsCRP was increased in adult asthmatics compared to HCs and was associated with several severity-related clinical characteristics. ICS use was associated with higher hsCRP levels in adults, potentially reflecting greater disease severity, whereas ICS use in preschool wheezers was associated with lower hsCRP levels. These age-dependent effects may mirror varying disease courses across the lifespan and progression of asthma. The association of hsCRP with asthma severity in child- and adulthood may indicate its potential relevance for the course of disease and monitoring clinical outcomes. Future longitudinal studies are needed to assess, whether hsCRP may support therapy monitoring. ClinicalTrials.gov; Pediatric arm: NCT02496468, Registration date: 03 July 2015; Adult arm: NCT02419274, Registration date: 14 April 2015.

Lena Lagally, Lena Ullemeyer, J. Omony et al. · 0 citations
Open access Aug 2026

In vitro metabolic signaling in two intestinal bacterial isolates: glutamate-driven transcriptional and functional reprogramming in Clostridium butyricum and Bacteroides thetaiotaomicron

ABSTRACT Monosodium glutamate (MSG; L-glutamate monosodium salt) is among the most widely used flavor enhancers, yet its molecular effects on gut microbial physiology remain poorly understood. Here, we examined the strain-specific transcriptomic and metabolic responses of Clostridium butyricum and Bacteroides thetaiotaomicron grown in pure anaerobic culture with 0.1% (wt/vol) MSG. Although MSG exposure was not associated with major changes in total bacterial biomass dynamics, both species showed a temporal functional reprogramming. In C. butyricum, MSG rapidly intensified metabolic activity to capitalize on exogenous glutamate by activating central carbon metabolism, redox-balancing pathways, and the GABA shunt, thereby collectively enhancing butyrate synthesis, a metabolite associated with gut barrier integrity, energy regulation, and anti-inflammatory signaling. On the other hand, B. thetaiotaomicron adopted a conservative, homeostatic response, suppressing glycan utilization and central carbon and energy metabolism, and maintaining stable SCFA production through controlled regulation that buffered against abrupt dietary perturbations. Overall, MSG functioned as a potent metabolic signal, triggering distinct adaptive strategies in two dominant gut bacteria. IMPORTANCE The impact of monosodium glutamate (MSG) as a highly consumed food additive on the gut microbiome is often overlooked, and community-level analyses reveal little change, masking distinct phenotypic responses of individual strains. By combining gene expression and metabolite profiling using two key human gut bacteria, we show that MSG is sensed as a metabolic signal. A butyrate-producing gut bacterium increases energy metabolism and butyrate production, and a fiber-degrading gut bacterium transiently moderates metabolism to maintain stable fermentation products. These differences suggest that MSG's physiological effects may depend on which bacterial groups dominate an individual’s microbiome. The impact of monosodium glutamate (MSG) as a highly consumed food additive on the gut microbiome is often overlooked, and community-level analyses reveal little change, masking distinct phenotypic responses of individual strains. By combining gene expression and metabolite profiling using two key human gut bacteria, we show that MSG is sensed as a metabolic signal. A butyrate-producing gut bacterium increases energy metabolism and butyrate production, and a fiber-degrading gut bacterium transiently moderates metabolism to maintain stable fermentation products. These differences suggest that MSG's physiological effects may depend on which bacterial groups dominate an individual’s microbiome.

Nazanin Nematzadeh Somehsaraei, Joshua Lemuel Hadi, M. Khan Mirzaei et al. · 0 citations