AUTHOR=Dhakal Samitinjaya , Dey Moul 

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

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.930414

DOI=10.3389/fnut.2022.930414

ISSN=2296-861X

ABSTRACT=<sec><title>Background</title><p>Resistant 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.</p></sec><sec><title>Methods and results</title><p>Using available plasma and stool samples from our previously reported double-blind, controlled, 2-arm crossover nutrition intervention trial (<ext-link ext-link-type="uri" xlink:href="http://Clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">Clinicaltrials.gov</ext-link>: 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 (<italic>n</italic> = 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, <italic>p</italic> &lt; 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 <italic>Bifidobacterium adolescentis</italic> with secondary BA such as, deoxycholic acid (rho = 0.55, <italic>p</italic> = 0.05), glycodeoxycholic acid (rho = 0.65, <italic>p</italic> = 0.02), and taurodeoxycholic acid (rho = 0.56, <italic>p</italic> = 0.04) were observed in the RS4-group, but not in the control group (all, <italic>p</italic> &gt; 0.05).</p></sec><sec><title>Conclusion</title><p>Our 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.</p></sec>