Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis.

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.

Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.

BACKGROUND/AIMS: Dietary restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may relieve symptoms in patients with irritable bowel syndrome (IBS). We investigated whether this diet alters microbial fermentation, a process that may be involved in IBS symptom generation. METHODS: Patients with IBS were included consecutively to participate in a 4-week FODMAP restricted diet. IBS symptoms were evaluated by using the IBS severity scoring system (IBS-SSS). Short-chain fatty acids (SCFAs) were analyzed in fecal samples before and after the dietary intervention, both at baseline and after in vitro fermentation for 24 h. RESULTS: Sixty-three patients completed the study. Following the dietary intervention, IBS-SSS scores improved significantly (p < 0.0001). Total SCFA levels were reduced in fecal samples analyzed both at baseline (p = 0.005) and after in vitro fermentation for 24 h (p = 0.013). Following diet, baseline levels of acetic (p = 0.003) and n-butyric acids (p = 0.009) decreased, whereas 24 h levels of i-butyric (p = 0.003) and i-valeric acids (p = 0.003) increased. Fecal SCFA levels and IBS symptom scores were not correlated. CONCLUSION: Dietary FODMAP restriction markedly modulated fecal fermentation in patients with IBS. Saccharolytic fermentation decreased, while proteolytic fermentation increased, apparently independent of symptoms.

Clinical importance of faecal calprotectin variability in inflammatory bowel disease: intra-individual variability and standardisation of sampling procedure.

OBJECTIVE: Faecal (f-) calprotectin is a biomarker of intestinal inflammation. Previous studies have described intra-individual day-to-day variability of this biomarker in patients with inflammatory bowel disease (IBD) and morning samples have been suggested for standardisation purposes. With this project, we investigated if day-to-day variability differed from diurnal variability. Additionally, we evaluated a new extraction method for f-calprotectin analysis. METHODS: Fifty patients provided three faeces samples from morning - evening - morning on two consecutive days. Nineteen patients provided two faeces samples from the same bowel movement, one conventional spot sample, and one sample with a device for patient-administered sampling and extraction. RESULTS: The two morning samples differentiated between mucosal inflammation and mucosal healing with same level of agreement as the two samples from the same day (kappa 0.76), using an f-calprotectin cut-off level of 259 µg/g. Although large intra-individual variation in f-calprotectin values, there were no significant day-to-day (p = 0.096) or diurnal variation (p = 0.78). Used by laboratory technicians, the new extraction device correlated significantly with the conventional extraction method (p < 0.001), Spearman's rank correlation coefficient 0.95. Of the 19 patients testing patient administered extraction, two patients provided samples leading to considerably higher f-calprotectin levels than conventional sampling procedure. CONCLUSIONS: The reliability of f-calprotectin morning samples is equal to the reliability of samples from different bowel movements on the same day. The new extraction method is reliable when used by laboratory technicians, but larger studies are recommended to evaluate patient administered extraction.