Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.

Background: Approximately 20% of patients with irritable bowel syndrome (IBS) link symptoms to food intake; a low-FODMAP diet is effective in managing these symptoms. Aims: To evaluate the effectiveness of the Mediterranean version of the low-FODMAP Diet (MED–LFD) compared to NICE guidelines for IBS and to assess changes in stool volatile compound levels. Methods: 108 patients with Rome IV IBS without constipation were randomized into the MED–LFD or NICE group. Primary endpoints included changes in symptom severity and responder rate (reduction of >50 IBS-SSS points) after intervention and at 6 months. Secondary endpoints assessed quality of life, symptom burden, adequate relief, anxiety/depression levels, and adherence. Volatile compound levels were measured using Gas Chromatography/Mass Spectrometry. Results: At both time points, the MED–LFD group showed a significantly greater improvement in symptom severity (159 ± 80 vs. 253 ± 94 and 168 ± 117 vs. 245 ± 98), responder rates (84.6% vs. 60.8% and 79.1% vs. 52.3%), and adherence (75% vs. 41% and 45% vs. 7%). Similar results were observed for all secondary endpoints, with no serious adverse events reported. The MED–LFD intervention was the strongest independent predictor of being a responder at the first (OR = 6.66; 95%CI = 1.46, 30.4) and second follow-up (OR = 4.85; 95%CI = 1.31, 17.96). Short and branched-chain fatty acids were significantly reduced at both follow-ups. Conclusions: The MED–LFD is superior to NICE recommendations in managing non-constipated IBS symptoms and quality of life. It remains to be proven that reduced volatile compound levels might be an objective marker of response to dietary interventions. ClinicalTrials.gov ID: NCT03997708.

Hydrogen sulfide (H₂S) is a gasotransmitter implicated in carbohydrate metabolism. This study explored associations between circulating H₂S, glucose homeostasis, and gut microbiome composition in type 2 diabetes mellitus (DM). Blood H₂S levels were quantified by HPLC in 93 DM patients; insulin resistance was assessed using HOMA-IR. Gut microbiota from 38 patients were analyzed via Oxford Nanopore 16S rRNA sequencing. Analyses were stratified by median H₂S and HbA1c values. Median H₂S and HbA1c levels were 22.65 μM and 7 %, respectively. Patients with H₂S ≥ 22.65 μM were more likely to have HbA1c ≥ 7 % (OR: 2.75; 95 % CI: 1.18–6.38; p = 0.022). Higher H₂S was linked to lower gut microbial diversity (Shannon index: 3.36 vs. 3.67, p = 0.021; Simpson index: 0.89 vs. 0.93, p = 0.007). Low H₂S was associated with higher relative abundance of Actinomycetota (p = 0.022). No microbiome differences were observed when stratified by HbA1c, and diabetes therapy was not linked to microbial diversity. Increased blood H₂S correlated with higher HbA1c and reduced microbial diversity, including decreased Actinomycetota. H₂S may represent a potential marker of poor glycemic control and gut microbiota alteration in DM.