Recent studies have shown a close relationship between the gut microbiota and Crohn’s disease (CD). This study aimed to determine whether mesenchymal stem cell (MSC) treatment alters the gut microbiota and fecal metabolite pathways and to establish the relationship between the gut microbiota and fecal metabolites. Patients with refractory CD were enrolled and received 8 intravenous infusions of MSCs at a dose of 1.0 × 106 cells/kg. The MSC efficacy and safety were evaluated. Fecal samples were collected, and their microbiomes were analyzed by 16S rDNA sequencing. The fecal metabolites at baseline and after 4 and 8 MSC infusions were identified by liquid chromatography-mass spectrometry (LC--MS). A bioinformatics analysis was conducted using the sequencing data. No serious adverse effects were observed. The clinical symptoms and signs of patients with CD were substantially relieved after 8 MSC infusions, as revealed by changes in weight, the CD activity index (CDAI) score, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). Endoscopic improvement was observed in 2 patients. A comparison of the gut microbiome after 8 MSC treatments with that at baseline showed that the genus Cetobacterium was significantly enriched. Linoleic acid was depleted after 8 MSC treatments. A possible link between the altered Cetobacterium abundance and linoleic acid metabolite levels was observed in patients with CD who received MSCs. This study enabled an understanding of both the gut microbiota response and bacterial metabolites to obtain more information about host-gut microbiota metabolic interactions in the short-term response to MSC treatment.
Pyroptosis is a programmed cell death caused by inflammation. Multiple studies have suggested that Mycobacterium tuberculosis infection causes tissue pyroptosis. However, there are currently no protective drugs against the inflammatory damage caused by pyroptosis. In this study, anti-pyroptotic effects of the natural compound astaxanthin (ASTA) were explored in a simulated pulmonary tuberculosis-associated inflammatory environment. The results showed that ASTA maintained the stability of MLE-12 lung epithelial cell numbers in the inflammatory environment established by lipopolysaccharide. The reason is not to promote cell proliferation but to inhibit lipopolysaccharide-induced pyroptosis. The results showed that ASTA significantly inhibited the expression of key proteins in the caspase 4/11-gasdermin D pathway and the release of pyroptosis-related inflammatory mediators. Therefore, ASTA inhibits inflammation-induced pyroptosis by inhibiting the caspase 4/11-gasdermin D pathway and has the potential to protect lung tissue from tuberculosis-related inflammatory injury. ASTA, a functional food component, is a promising candidate for protection against tuberculosis-associated inflammatory lung injury.
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