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Abstract Effective early-stage markers for predicting which patients are at risk of developing SARS-CoV-2 infection have not been fully investigated. Here, we performed comprehensive serum metabolome analysis of a total of 83 patients from two cohorts to determine that the acceleration of amino acid catabolism within 5 days from disease onset correlated with future disease severity. Increased levels of de-aminated amino acid catabolites involved in the de novo nucleotide synthesis pathway were identified as early prognostic markers that correlated with the initial viral load. We further employed mice models of SARS-CoV2-MA10 and influenza infection to demonstrate that such de-amination of amino acids and de novo synthesis of nucleotides were associated with the abnormal proliferation of airway and vascular tissue cells in the lungs during the early stages of infection. Consequently, it can be concluded that lung parenchymal tissue remodeling in the early stages of respiratory viral infections induces systemic metabolic remodeling and that the associated key amino acid catabolites are valid predictors for excessive inflammatory response in later disease stages.

Inflammatory bowel disease (IBD) is a chronic disease characterised by repeated relapses and remissions and a high recurrence rate even after symptom resolution. The primary method for IBD diagnosis is endoscopy; however, this method is expensive, invasive, and cumbersome to use serially. Therefore, more convenient and non-invasive methods for IBD diagnosis are needed. In this study, we aimed to identify biological gas markers for the development of gut inflammation. Using dextran sulphate sodium (DSS)-induced colitis mouse models, five biological gases were analysed to identify predictive markers for the development of gut inflammation. Additionally, the correlation between the changes in gas composition, gut microbiota, and inflammatory markers was assessed. The hydrogen (H2) level was found to be negatively correlated with the level of lipocalin-2 (LCN2), a gut inflammation biomarker, and weight loss due to DSS-induced colitis. Furthermore, gut microbes belonging to the Rikenellaceae and Akkermansiaceae families were positively correlated with LCN2 levels and weight loss, whereas Tannerellaceae abundance was negatively correlated with LCN2 level and weight loss and positively correlated with H2 levels. This study provides new insights for IBD diagnosis; the H2 levels in biological gases are a potential biomarker for intestinal inflammation, and specific gut microbes are associated with H2 level changes.

BackgroundFecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate.Methods and AnalysisThis trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint.DiscussionThe FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC.Clinical Trial Registrationhttps://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.