Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study


      The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD.

      Design and Methods

      In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m2, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate.


      At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate.


      A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Renal Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Fraher M.H.
        • O'Toole P.W.
        • Quigley E.M.
        Techniques used to characterize the gut microbiota: a guide for the clinician.
        Nat Rev Gastroenterol Hepatol. 2012; 9: 312-322
        • Gill S.R.
        • Pop M.
        • Deboy R.T.
        • et al.
        Metagenomic analysis of the human distal gut microbiome.
        Science. 2006; 312: 1355-1359
        • Stearns J.C.
        • Lynch M.D.
        • Senadheera D.B.
        • et al.
        Bacterial biogeography of the human digestive tract.
        Sci Rep. 2011; 1: 170
        • Tang W.H.
        • Wang Z.
        • Kennedy D.J.
        • et al.
        Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease.
        Circ Res. 2015; 116: 448-455
        • Meijers B.
        • Evenepoel P.
        • Anders H.J.
        Intestinal microbiome and fitness in kidney disease.
        Nat Rev Nephrol. 2019; 15: 531-545
        • Ramezani A.
        • Massy Z.A.
        • Meijers B.
        • Evenepoel P.
        • Vanholder R.
        • Raj D.S.
        Role of the gut microbiome in uremia: a potential Therapeutic Target.
        Am J Kidney Dis. 2016; 67: 483-498
        • Vaziri N.D.
        • Wong J.
        • Pahl M.
        • et al.
        Chronic kidney disease alters intestinal microbial flora.
        Kidney Int. 2013; 83: 308-315
        • Wong J.
        • Piceno Y.M.
        • DeSantis T.Z.
        • Pahl M.
        • Andersen G.L.
        • Vaziri N.D.
        Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD.
        Am J Nephrol. 2014; 39: 230-237
        • Evenepoel P.
        • Meijers B.K.
        • Bammens B.R.
        • Verbeke K.
        Uremic toxins originating from colonic microbial metabolism.
        Kidney Int Suppl. 2009; : S12-S19
        • Meijers B.K.
        • De Preter V.
        • Verbeke K.
        • Vanrenterghem Y.
        • Evenepoel P.
        p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin.
        Nephrol Dial Transpl. 2010; 25: 219-224
        • Rossi M.
        • Johnson D.W.
        • Xu H.
        • et al.
        Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients.
        Nutr Metab Cardiovasc Dis. 2015; 25: 860-865
        • Lin C.J.
        • Wu V.
        • Wu P.C.
        • Wu C.J.
        Meta-analysis of the associations of p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with cardiovascular Events and all-Cause mortality in patients with chronic renal failure.
        PLoS One. 2015; 10: e0132589
        • Barreto F.C.
        • Barreto D.V.
        • Canziani M.E.
        • et al.
        Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients.
        J Bras Nefrol. 2014; 36: 289-296
        • Poesen R.
        • Evenepoel P.
        • de Loor H.
        • Kuypers D.
        • Augustijns P.
        • Meijers B.
        Metabolism, protein binding, and renal Clearance of microbiota-derived p-cresol in patients with CKD.
        Clin J Am Soc Nephrol. 2016; 11: 1136-1144
        • Luis D.
        • Zlatkis K.
        • Comenge B.
        • et al.
        Dietary quality and adherence to dietary recommendations in patients undergoing hemodialysis.
        J Ren Nutr. 2016; 26: 190-195
        • de Loor H.
        • Poesen R.
        • De Leger W.
        • et al.
        A liquid chromatography - tandem mass spectrometry method to measure a selected panel of uremic retention solutes derived from endogenous and colonic microbial metabolism.
        Anal Chim Acta. 2016; 936: 149-156
        • Alexander C.
        • Swanson K.S.
        • Fahey Jr., G.C.
        • Garleb K.A.
        Perspective: physiologic importance of short-chain fatty acids from Nondigestible carbohydrate fermentation.
        Adv Nutr. 2019; 10: 576-589
        • Pluznick J.L.
        Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors.
        Kidney Int. 2016; 90: 1191-1198
        • Jama H.A.
        • Beale A.
        • Shihata W.A.
        • Marques F.Z.
        The effect of diet on hypertensive pathology: is there a link via gut microbiota-driven immunometabolism?.
        Cardiovasc Res. 2019; 115: 1435-1447
        • Kaye D.M.
        • Shihata W.
        • Jama H.A.
        • et al.
        Deficiency of prebiotic Fibre and Insufficient Signalling through gut metabolite Sensing receptors leads to cardiovascular disease.
        Circulation. 2020; 141: 1393-1403
        • David L.A.
        • Maurice C.F.
        • Carmody R.N.
        • et al.
        Diet rapidly and reproducibly alters the human gut microbiome.
        Nature. 2014; 505: 559-563
        • Biruete A.
        • Jeong J.H.
        • Barnes J.L.
        • Wilund K.R.
        Modified Nutritional recommendations to Improve dietary patterns and outcomes in hemodialysis patients.
        J Ren Nutr. 2017; 27: 62-70
        • Kelly J.T.
        • Palmer S.C.
        • Wai S.N.
        • et al.
        Healthy dietary patterns and risk of mortality and ESRD in CKD: a Meta-analysis of cohort studies.
        Clin J Am Soc Nephrol. 2017; 12: 272-279
        • Roberfroid M.B.
        Inulin-type fructans: functional food ingredients.
        J Nutr. 2007; 137: 2493S
        • Gibson G.R.
        • Hutkins R.
        • Sanders M.E.
        • et al.
        Expert consensus document: the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.
        Nat Rev Gastroenterol Hepatol. 2017; 14: 491-502
        • Pokusaeva K.
        • Fitzgerald G.F.
        • van Sinderen D.
        Carbohydrate metabolism in bifidobacteria.
        Genes Nutr. 2011; 6: 285-306
        • Selak M.
        • Riviere A.
        • Moens F.
        • et al.
        Inulin-type fructan fermentation by bifidobacteria depends on the strain rather than the species and region in the human intestine.
        Appl Microbiol Biotechnol. 2016; 100: 4097-4107
        • Scott K.P.
        • Martin J.C.
        • Duncan S.H.
        • Flint H.J.
        Prebiotic stimulation of human colonic butyrate-producing bacteria and bifidobacteria, in vitro.
        FEMS Microbiol Ecol. 2014; 87: 30-40
        • Chung W.S.
        • Walker A.W.
        • Louis P.
        • et al.
        Modulation of the human gut microbiota by dietary fibres occurs at the species level.
        BMC Biol. 2016; 14: 3
        • Biruete A.
        Effects of inulin supplementation on markers of mineral and bone metabolism and the gut microbiota in hemodialysis patients. Urbana, IL, USA: University of Illinois at Urbana-Champaign; 2017.
        • Institute of Medicine
        Dietary Reference Intakes: The Essential Guide to Nutrition Requirements.
        The National Academies Press, Washington, DC2006
        • Lewis S.J.
        • Heaton K.W.
        Stool form scale as a useful guide to intestinal transit time.
        Scand J Gastroenterol. 1997; 32: 920-924
        • Caporaso J.G.
        • Lauber C.L.
        • Walters W.A.
        • et al.
        Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample.
        Proc Natl Acad Sci U S A. 2011; 108: 4516-4522
        • Edgar R.C.
        Search and clustering orders of magnitude faster than BLAST.
        Bioinformatics. 2010; 26: 2460-2461
        • DeSantis T.Z.
        • Hugenholtz P.
        • Larsen N.
        • et al.
        Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB.
        Appl Environ Microbiol. 2006; 72: 5069-5072
        • Lozupone C.
        • Knight R.
        UniFrac: a new phylogenetic method for comparing microbial communities.
        Appl Environ Microbiol. 2005; 71: 8228-8235
        • Erwin ESM G.J.
        • Emery E.M.
        Volatile fatty acid analyses of blood and rumen fluid by gas chromatography.
        J Dairy Sci. 1961; 44: 1768-1771
        • Flickinger E.A.
        • Schreijen E.M.
        • Patil A.R.
        • et al.
        Nutrient digestibilities, microbial populations, and protein catabolites as affected by fructan supplementation of dog diets.
        J Anim Sci. 2003; 81: 2008-2018
        • (AOAC) AoOAC
        Official methods of analysis.
        17th Edition. Assoc. Off. Anal. Chem., Gaithersburg, MD2006
        • Murphy S.P.
        Collection and analysis of intake data from the integrated survey.
        J Nutr. 2003; 133: 585S-589S
        • Vandeputte D.
        • Falony G.
        • Vieira-Silva S.
        • et al.
        Prebiotic inulin-type fructans induce specific changes in the human gut microbiota.
        Gut. 2017; 66: 1968-1974
        • Langille M.G.
        • Zaneveld J.
        • Caporaso J.G.
        • et al.
        Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences.
        Nat Biotechnol. 2013; 31: 814-821
        • Holscher H.D.
        • Bauer L.L.
        • Gourineni V.
        • Pelkman C.L.
        • Fahey Jr., G.C.
        • Swanson K.S.
        Agave inulin supplementation affects the fecal microbiota of healthy adults Participating in a randomized, double-blind, placebo-controlled, crossover trial.
        J Nutr. 2015; 145: 2025-2032
        • Salazar N.
        • Dewulf E.M.
        • Neyrinck A.M.
        • et al.
        Inulin-type fructans modulate intestinal Bifidobacterium species populations and decrease fecal short-chain fatty acids in obese women.
        Clin Nutr. 2015; 34: 501-507
        • Dewulf E.M.
        • Cani P.D.
        • Claus S.P.
        • et al.
        Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women.
        Gut. 2013; 62: 1112-1121
        • Guess N.D.
        • Dornhorst A.
        • Oliver N.
        • Frost G.S.
        A Randomised crossover trial: the effect of inulin on Glucose Homeostasis in Subtypes of Prediabetes.
        Ann Nutr Metab. 2016; 68: 26-34
        • Dehghan P.
        • Pourghassem Gargari B.
        • Asghari Jafar-abadi M.
        Oligofructose-enriched inulin improves some inflammatory markers and metabolic endotoxemia in women with type 2 diabetes mellitus: a randomized controlled clinical trial.
        Nutrition. 2014; 30: 418-423
        • Li L.
        • Xiong Q.
        • Zhao J.
        • et al.
        Inulin-type fructan intervention restricts the increase in gut microbiome-generated indole in patients with peritoneal dialysis: a randomized crossover study.
        Am J Clin Nutr. 2020; 111: 1087-1099
        • Macfarlane G.T.
        • Macfarlane S.
        Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics.
        J Clin Gastroenterol. 2011; 45: S120-S127
        • Lun H.
        • Yang W.
        • Zhao S.
        • et al.
        Altered gut microbiota and microbial biomarkers associated with chronic kidney disease.
        Microbiologyopen. 2019; 8: e00678
        • Henke M.T.
        • Kenny D.J.
        • Cassilly C.D.
        • Vlamakis H.
        • Xavier R.J.
        • Clardy J.
        Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn's disease, produces an inflammatory polysaccharide.
        Proc Natl Acad Sci U S A. 2019; 116: 12672-12677
        • Olano-Martin E.
        • Mountzouris K.C.
        • Gibson G.R.
        • Rastall R.A.
        In vitro fermentability of dextran, oligodextran and maltodextrin by human gut bacteria.
        Br J Nutr. 2000; 83: 247-255
        • Abrams S.A.
        • Griffin I.J.
        • Hawthorne K.M.
        • et al.
        A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents.
        Am J Clin Nutr. 2005; 82: 471-476
        • Poesen R.
        • Evenepoel P.
        • de Loor H.
        • et al.
        The Influence of prebiotic Arabinoxylan Oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: a randomized controlled trial.
        PLoS One. 2016; 11: e0153893
        • Ramos C.I.
        • Armani R.G.
        • Canziani M.E.F.
        • et al.
        Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial.
        Nephrol Dial Transpl. 2018;
        • Warren F.J.
        • Fukuma N.M.
        • Mikkelsen D.
        • et al.
        Food Starch Structure impacts gut microbiome composition.
        mSphere. 2018; 3
        • Devlin A.S.
        • Marcobal A.
        • Dodd D.
        • et al.
        Modulation of a circulating uremic Solute via Rational Genetic Manipulation of the gut microbiota.
        Cell Host Microbe. 2016; 20: 709-715
        • Peters B.A.
        • Shapiro J.A.
        • Church T.R.
        • et al.
        A taxonomic signature of obesity in a large study of American adults.
        Sci Rep. 2018; 8: 9749
        • Zhao L.
        The gut microbiota and obesity: from correlation to causality.
        Nat Rev Microbiol. 2013; 11: 639-647
        • Ketteler M.
        • Block G.A.
        • Evenepoel P.
        • et al.
        Diagnosis, Evaluation, Prevention, and treatment of chronic kidney disease-mineral and bone disorder: Synopsis of the kidney disease: Improving Global outcomes 2017 clinical Practice Guideline Update.
        Ann Intern Med. 2018; 168: 422-430
        • Biruete A.
        • Hill Gallant K.M.
        • Lindemann S.R.
        • Wiese G.N.
        • Chen N.X.
        • Moe S.M.
        Phosphate binders and Nonphosphate effects in the gastrointestinal tract.
        J Ren Nutr. 2019;
        • Schmid H.
        • Hartmann B.
        • Schiffl H.
        Adherence to prescribed oral medication in adult patients undergoing chronic hemodialysis: a critical review of the literature.
        Eur J Med Res. 2009; 14: 185-190
        • Holscher H.D.
        • Doligale J.L.
        • Bauer L.L.
        • et al.
        Gastrointestinal tolerance and utilization of agave inulin by healthy adults.
        Food Funct. 2014; 5: 1142-1149
        • Biruete A.
        • Kistler B.M.
        • Allen J.
        • Bauer L.L.
        • Fahey G.C.
        • Swanson K.S.
        • et al.
        Effects of inulin supplementation on mineral metabolism and fecal short-chain fatty acid excretion in hemodialysis patients.
        Nephrol Dial Transpl. 2017; 32
      1. Biruete A, Kistler BM, Cross TL, Allen J, de Loor H, Evenepoel P, et al. Effect of Dietary Inulin Supplementation on the Gut Microbiota and Derived Metabolites in Hemodialysis Patients. XIX International Congress on Nutrition and Metabolism in Renal Disease; Genoa, IT2018.