Resistant starch type-4 intake alters circulating bile acids in human subjects

Abstract

BackgroundResistant starch (RS) type 4 (RS4) is a type of RS, a class of non-digestible prebiotic dietary fibers with a range of demonstrated metabolic health benefits to the host. On the other hand, bile acids (BA) have recently emerged as an important class of metabolic function mediators that involve host-microbiota interactions. RS consumption alters fecal and cecal BA in humans and rodents, respectively. The effect of RS intake on circulating BA concentrations remains unexplored in humans.Methods and resultsUsing available plasma and stool samples from our previously reported double-blind, controlled, 2-arm crossover nutrition intervention trial (Clinicaltrials.gov: NCT01887964), a liquid-chromatography/mass-spectrometry-based targeted multiple reaction monitoring, and absolute quantifications, we assessed BA changes after 12 weeks of an average 12 g/day RS4-intake. Stool BA concentrations were lower post RS4 compared to the control, the two groups consuming similar macronutrients (n = 14/group). Partial least squares-discriminant analysis revealed distinct BA signatures in stool and plasma post interventions. The increased circulating BA concentrations were further investigated using linear mixed-effect modeling that controlled for potential confounders. A higher plasma abundance of several BA species post RS4 was observed (fold increase compared to control in parenthesis): taurocholic acid (1.92), taurodeoxycholic acid (1.60), glycochenodeoxycholic acid (1.58), glycodeoxycholic acid (1.79), and deoxycholic acid (1.77) (all, p < 0.05). Distinct microbiome ortholog-signatures were observed between RS4 and control groups (95% CI), derived using the Piphillin function-prediction algorithm and principal component analysis (PCA) of pre-existing 16S rRNA gene sequences. Association of Bifidobacterium adolescentis with secondary BA such as, deoxycholic acid (rho = 0.55, p = 0.05), glycodeoxycholic acid (rho = 0.65, p = 0.02), and taurodeoxycholic acid (rho = 0.56, p = 0.04) were observed in the RS4-group, but not in the control group (all, p > 0.05).ConclusionOur observations indicate a previously unknown in humans- RS4-associated systemic alteration of microbiota-derived secondary BA. Follow-up investigations of BA biosynthesis in the context of RS4 may provide molecular targets to understand and manipulate microbiome-host interactions.

Harnessing the power of resistant starch: a narrative review of its health impact and processing challenges

“…Overall, the benefits of the different types of RS are likely exerted through different pathways ( 64 ), as demonstrated by the varying microbiota responses to different types of RS. For instance, after 12 weeks of consuming 12 g of RS4 daily, a significant decrease in bile acid in stools were reported compared to control ( 79 ). In an in vitro study, both RS2 and RS4 in rice sticks led to significantly higher counts of Bifidobacterium and Lactobacillus compared to the control food under pH-controlled batch culture conditions.…”

Human gut microbiome: Therapeutic opportunities for metabolic syndrome—Hype or hope?

“…While in adults no convincing effect on body weight could be observed, in obese children inulin and dietary fibre together with increased exercise showed a significant decrease in weight and body fat 109 . Resistant starch type 4 (RS4) supplementation positively affected lipid metabolism, potentially by modulating bile acid metabolism and microbiome composition, but not glucose metabolism 110–112 . The addition of polyphenolic food components increased butyrate‐producing gut bacteria and influenced the composition of the microbiome; however, the effects were largely dependent on the concomitant medication of patients 113–115 .…”

“… 109 Resistant starch type 4 (RS4) supplementation positively affected lipid metabolism, potentially by modulating bile acid metabolism and microbiome composition, but not glucose metabolism. 110 , 111 , 112 The addition of polyphenolic food components increased butyrate‐producing gut bacteria and influenced the composition of the microbiome; however, the effects were largely dependent on the concomitant medication of patients. 113 , 114 , 115 Taken together, prebiotics seem to modify gut microbiome composition but the effects on metabolic syndrome markers and body weight are rare.…”

Oat as a Source of Resistant Starch: A Review

“…Dextrinization, etherification, esterification, oxidation, and cross-linking with difunctional reagents are among the chemistries that hinder amylolysis. These chemistries can significantly alter the food engineering functionality that the RS contributes to the food, such as solubility and process tolerance (Dhakal & Dey, 2022). In addition to resisting heating and amylase enzyme hydrolysis, RS5 offers steady processing qualities that minimize the swelling of starch granules.…”