Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome

Abstract

INTRODUCTION: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. METHODS: We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. RESULTS: Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [−0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). DISCUSSION: Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.

Association between fecal short-chain fatty acid levels and constipation severity in subjects with slow transit constipation

“…Previous findings [14,15] have reported that the relief of constipation altered the composition of colonic microbiota and increased intestinal SCFA levels. Mohammed et al [16] reported that fecal SCFA levels are correlated with colonic transit. However, the patients were not diagnosed with STC and some studies included patients who had irritable bowel syndrome with diarrhea.…”

“…SCFA levels were lower in STC subjects than in healthy subjects, but the difference was not statistically significant (475.85 ± 251.68 µg/ ml vs. 639.77 ± 213.97 µg/ml, P = 0.056). Compared to healthy subjects, STC subjects had lower fecal levels of acetic and propionic acids (149.06 ± 88.54 µg/ml vs. 261.33 ± 109.75 µg/ml and100.60 ± 60.62 µg/ml vs. 157.34 ± 66.37 µg/ml, respectively, P < 0.05) and higher levels of isobutyric and isovaleric acids (27.21 ± 15.06 µg/ ml vs. 18.16 ± 8.65 µg/ml and 31.78 ± 18.81 µg/ml vs. 16.90 ± 10.05 µg/ml, P < 0.05; Fig. 1b).…”

Microbiota-Short Chain Fatty Acid Relationships Underlie Clinical Heterogeneity and Identify Key Microbial Targets in Irritable Bowel Syndrome (IBS)

“…We have previously shown that transit and BAM correlate with SCFA excretion in IBS. 27 Others have reported that microbiome associations with transit are largely influenced by altered bile acid biotransformation. 19 In this current study, several bacterial species with fermentative capacity or varied substrate processing functions correlated with total stool SCFA, but not with transit or bile acids.…”

“…Accordingly, studies 10,15,24 that have assessed stool SCFA in distinct IBS subgroups have reported more consistent associations of stool SCFA with IBS subtypes as well as correlations of stool SCFA with measurable IBS traits such as colonic transit, bowel functions, and bile acid excretion. [24][25][26][27] Despite these reports, the intercorrelation between SCFA, bile acids, and transit time complicates the assessment of whether microbial composition is directly responsible for SCFA profiles or if relationships between the intestinal microbiome and excreted SCFA is clinically valuable due to the complex and dynamic nature of the microbial ecosystem. However, recent work 28 has suggested that individual taxa, rather than complex ecological communities, could drive changes in SCFA output in response to dietary fiber.…”

Can physical exercise help people with irritable bowel syndrome? How substantial is the evidence?

“…Moreover, increasing stress hormones such as corticosteroids and catecholamines induced by exercise can negatively affect gut motility, microbiota, and SCF production and reduce GI transport activity [66]. Thus, decreasing SCF can result in dysregulation of visceral sensation and associate with constipation and IBS symptoms [67].…”