The short-chain fatty acid (SCFA) butyric acid maintains a healthy gut barrier and vascular endothelium. We aimed to investigate the association between fecal butyric acid, carotid atherosclerosis and risk factors for ischemic stroke. Patients with severe carotid atherosclerosis (i.e. ≥ 50% stenosis) (n = 43) were compared with healthy controls (n = 38). We analyzed fecal SCFAs by gas chromatography, microbiota composition by 16S rRNA sequencing, markers of gut barrier damage and inflammasome activation by immunoassay, and plasma SCFAs by ultra-high performance liquid chromatography-tandem mass spectroscopy. Patients had higher fecal butyric acid level (p = 0.024), along with increased functional potential of microbial butyric acid production (p = 0.031), compared with controls. Dietary fiber intake was comparable. Patients had higher levels of gut barrier damage markers CCL25 and IFABP, and the inflammasome activation marker IL-18, whereas plasma level of butyric was similar. Increased fecal butyric acid was associated with higher BMI, waist-hip ratio, HbA1c, CRP and leukocyte count. Contrary to our hypothesis, patients with severe carotid atherosclerosis had higher fecal butyric acid level, and increased microbial production, compared with controls. Gut barrier damage in patients might indicate decreased absorption of butyric acid and hence contribute to the higher fecal level.

HIV and type 2 diabetes (T2D) are both associated with gut microbiota alterations, low-grade endotoxemia and increased cardiovascular risk. We investigated the potential role of plasma extracellular vesicles (EVs) in relation to these processes. Plasma EVs were isolated by size exclusion chromatography in fasting individuals with HIV and T2D (n = 16), T2D only (n = 14), HIV only (n = 20) or healthy controls (n = 19), and characterized by transmission electron microscopy, western blot, nanoparticle tracking analysis and quantitative proteomics. The findings were compared to gut microbiota alterations, lipopolysaccharide levels and cardiovascular risk profile. Individuals with concomitant HIV and T2D had higher plasma EV concentration, which correlated closely with plasma lipopolysaccharides, triglycerides and Framingham score, but not with gut microbiota alterations. Proteomic analyses identified 558 human proteins, largely related to cardiometabolic disease genes and upstream regulation of inflammatory pathways, including IL-6 and IL-1β, as well as 30 bacterial proteins, mostly from lipopolysaccharide-producing Proteobacteria. Our study supports that EVs are related to microbial translocation processes in individuals with HIV and T2D. Their proteomic content suggests a contributing role in low-grade inflammation and cardiovascular risk development. The present approach for exploring gut-host crosstalk can potentially identify novel diagnostic biomarkers and therapeutic targets.

Objective: Although COVID-19 is primarily a respiratory infection, mounting evidence suggests that the GI tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and could be related to long-term respiratory dysfunction is unknown. Design: From the NOR-Solidarity trial (n=181), plasma was collected during hospital admission and after three months, and analyzed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring diffusing capacity of the lungs for carbon monoxide (DL _CO ), and rectal swabs for gut microbiota analyses were collected (n= 97) and analysed by sequencing of the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with persistent respiratory dysfunction, defined as DL _CO below lower limit of normal three months after hospitalization. These patients also had an altered global gut microbiota composition, with reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Flavonifractor and Veillonella , the latter potentially being linked to fibrosis. During hospitalization, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO ₂ /fiO ₂ -(P/F-ratio)<26.6 kPa. LBP levels remained elevated during and after hospitalization, and was associated with low-grade inflammation and persistent respiratory dysfunction after three months. Conclusion: Persistent respiratory dysfunction after COVID-19 is associated with reduced biodiversity and gut microbiota alterations, along with persistently elevated LBP levels. Our results point to a potential gut-lung axis that should be further investigated in relation to long-term pulmonary dysfunction and long COVID. Summary box: What is already known about this subject?: Mounting evidence suggests that the gastrointestinal tract is involved in the pathogenesis of COVID-19, with the putative SARS-CoV-2 receptor ACE 2 ubiquitously expressed in the gut. In severe COVID-19, the gut-blood barrier is compromised, and leakage of microbial products, such as lipopolysaccharides (LPS), could affect the host’s response to COVID-19 infection. COVID-19 patients exhibit an altered gut microbiota composition, which has been related to disease severity. However, it is currently not known whether dysbiosis or gut barrier dysfunction persist long-term after hospitalization, or whether microbiota-related mechanisms could be related to persistent pulmonary dysfunction. What are the new findings?: COVID-19 patients with persistent respiratory dysfunction after three months had a lower microbial diversity and an altered gut microbiota composition at the same time point. The microbiota alterations included reduced abundance of Erysipelotrichaceae UCG-003 and increased abundance of Veillonella and Flavonifractor . During hospitalization, increased plasma levels of LBP were strongly associated with respiratory failure. LBP levels remained elevated during and after hospitalization, and associated significantly with persistent respiratory dysfunction at three-month follow-up. How might it impact on clinical practice in the foreseeable future?: Our findings point to a potential gut-lung axis in relation not only to respiratory failure during hospitalization, but also to long-term COVID-19 morbidity. Further studies on gut microbiota composition and gut barrier dysfunction as potential treatment targets and/or disease severity biomarkers in relation to long-term pulmonary dysfunction and long COVID are warranted.

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis (UC), are characterized by chronic gastrointestinal inflammation and involve complex interactions of genetic, environmental, and immune factors. Enterococcus faecalis, a gut commensal bacterium, has been implicated in IBD pathogenesis. This study investigated the effects of monocolonization with a UC-derived E. faecalis strain on acute dextran sulfate sodium (DSS)-induced colitis in germ-free (GF) mice, focusing on epithelial injury, inflammatory markers, hematologic indices, and bacterial translocation. In DSS-treated mice, monocolonization was associated with modest and mixed effects, including a higher colitis-related disease activity score, reduced anemia, increased fecal albumin and a trend towards reduced fecal calprotectin. Despite translocation of E. faecalis to mesenteric lymph nodes, no systemic dissemination was observed. Histological analysis revealed broadly similar inflammatory patterns between DSS-treated groups, with slightly more epithelial injury observed in colonized mice. These findings suggest that E. faecalis may influence discrete aspects of DSS injury in a strain-dependent and context-specific manner, rather than broadly altering overall disease severity. This study highlights the utility of GF models for examining strain-specific host–microbe interactions and underscores that individual bacterial isolates may exert heterogeneous and selective effects on acute colitis. Further research is needed to elucidate these complex mechanisms.

Background: HIV and type 2 diabetes (T2D) are both associated with gut microbiota alterations, low-grade endotoxemia and increased cardiovascular risk. We investigated the potential role of plasma extracellular vesicles (EVs) in relation to these processes. Materials and methods: Plasma EVs were isolated by size exclusion chromatography in fasting individuals with HIV and T2D (n=16), T2D only (n=14), HIV only (n=20) or healthy controls (n=19), and characterized by transmission electron microscopy, western blot, nanoparticle tracking analysis and quantitative proteomics. The findings were compared to gut microbiota alterations, lipopolysaccharide levels and cardiovascular risk profile. Results: Individuals with concomitant HIV and T2D had higher plasma EV concentration, which correlated closely with plasma lipopolysaccharides, triglycerides and Framingham score, but not with gut microbiota alterations. Proteomic analyses identified 558 human proteins, largely related to cardiometabolic disease genes and upstream regulation of inflammatory pathways, including IL-6 and IL-1β, as well as 30 bacterial proteins, mostly from lipopolysaccharide-producing Proteobacteria. Conclusions: Our study supports that EVs are related to microbial translocation processes in individuals with HIV and T2D. Their proteomic content suggests a contributing role in low-grade inflammation and cardiovascular risk development. The present approach for exploring gut-host crosstalk can potentially identify novel diagnostic biomarkers and therapeutic targets.