Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels-a randomized controlled trial in healthy individuals

Vibeke H Telle-Hansen, Line Gaundal, Nasser Bastani, Ida Rud, Marte G Byfuglien, Terje Gjøvaag, Kjetil Retterstøl, Kirsten B Holven, Stine M Ulven, Mari C W Myhrstad, Vibeke H Telle-Hansen, Line Gaundal, Nasser Bastani, Ida Rud, Marte G Byfuglien, Terje Gjøvaag, Kjetil Retterstøl, Kirsten B Holven, Stine M Ulven, Mari C W Myhrstad

Abstract

Background: Improving dietary fat quality strongly affects serum cholesterol levels and hence the risk of cardiovascular diseases (CVDs). Recent studies have identified dietary fat as a potential modulator of the gut microbiota, a central regulator of host metabolism including lipid metabolism. We have previously shown a significant reduction in total cholesterol levels after replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs). The aim of the present study was to investigate the effect of dietary fat quality on gut microbiota, short-chain fatty acids (SCFAs), and bile acids in healthy individuals. In addition, to investigate how changes in gut microbiota correlate with blood lipids, bile acids, and fatty acids.

Methods: Seventeen participants completed a randomized, controlled dietary crossover study. The participants received products with SFAs (control) or PUFAs in random order for three days. Fecal samples for gut microbiota analyses and fasting blood samples (lipids, fatty acids, and bile acids) were measured before and after the three-day intervention.

Results: Of a panel of 40 bacteria, Lachnospiraceae and Bifidobacterium spp. were significantly increased after intervention with PUFAs compared with SFAs. Interestingly, changes in Lachnospiraceae, as well as Phascolarlactobacterium sp. and Eubacterium hallii, was also found to be negatively correlated with changes in total cholesterol levels after replacing the intake of SFAs with PUFAs for three days. No significant differences in SCFAs or bile acids were found after the intervention.

Conclusion: Replacing SFAs with PUFAs increased the abundance of the gut microbiota family of Lachnospiraceae and Bifidobacterium spp. Furthermore, the reduction in total cholesterol after improving dietary fat quality correlated with changes in the gut microbiota family Lachnospiraceae. Future studies are needed to reveal whether Lachnospiraceae may be targeted to reduce total cholesterol levels.

Trial registration: The study was registered at Clinical Trials ( https://ichgcp.net/clinical-trials-registry/NCT03658681" title="See in ClinicalTrials.gov">NCT03658681).

Keywords: Dietary fat; Gut microbiota; Lachnospiraceae; Polyunsaturated fatty acids; Randomized controlled trial; Total cholesterol.

Conflict of interest statement

LG, NB, TG and IR report nothing to declare. VHTH has been employed at Mills AS and reports grants from Mills AS. She does not own any stocks in the company, and the work performed in this paper was done after she left the company. MGB is employed at Mills AS. She does not own any stocks in the company. She did not have a role in the design of the study and analysis of the data and was not involved in the statistical analysis. KR reports personal fees from MedXplore, Amgen, Mills AS, The Norwegian Medical Association, The Norwegian Directorate of Health, Sanofi, Takeda, Chiesi, Bayer and MSD, outside the submitted work. KBH reports grants from Tine SA, Mills AS, Olympic Seafood, Amgen, Sanofi, Kaneka and personal fees from Amgen, Sanofi, Pronova, outside the submitted work. SMU has received research grants from Tine DA, Mills AS, and Olympic Seafood, none of which are related to the content of this manuscript. MCWM is involved in projects with research grants from Tine SA and Olympic Seafood and has received research funds from Mills AS, none of which are related to the content of this manuscript.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart of the participants included in the dietary crossover study (n = 17) [1]. Abbreviations: n: number; PUFAs: polyunsaturated fatty acids; SFAs: saturated fatty acids
Fig. 2
Fig. 2
Study design of the double-blind, randomized, controlled crossover study. Described previously [1]. Seventeen healthy volunteers (group 1: n = 9; group 2: n = 8) received daily PUFA products (two muffins and 20 g margarine spread) or SFA products (two muffins and 20 g butter-based spread) for three consecutive days, separated by a 1.5-week washout period. The participants received SFA products in the run-in and washout periods. Fasted blood was measured for glucose, insulin, triglyceride, NEFAs, fatty acid profiles, SCFAs, bile acids, and total cholesterol at each visit. In addition, fecal samples were collected for gut microbiota analyses at each visit. Abbreviations: NEFAs: nonesterified fatty acids, PUFAs: polyunsaturated fatty acids, SCFAs: short-chain fatty acids, SFAs: saturated fatty acids
Fig. 3
Fig. 3
SCFAs before and after intake of SFAs or PUFAs. Total SCFAs and relative levels of acetate, propionate, and butyrate before (day 1) and after (day 4) intake of SFAs and PUFAs in healthy individuals (n = 17) for three consecutive days. Data are shown as the median, and bars indicate the 25th—75th percentiles. Within- and between-group differences were analyzed with the Wilcoxon signed rank test. * indicates P ≤ 0.05. Abbreviations: PUFAs: polyunsaturated fatty acids, SCFAs: short-chain fatty acids, SFAs: saturated fatty acids
Fig. 4
Fig. 4
Relationship between changes in gut bacteria and total cholesterol, triglycerides, NEFAs, SCFAs, bile acids, and fatty acid profiles after intervention with SFAs and PUFAs. Correlation analysis was performed with Pearson correlation. * indicates P ≤ 0.05. Abbreviations: C12:0: lauric acid, C14:0: myristic acid, C16:0: palmitic acid, C18:3 n3: alpha-linolenic acid, C20:5 n3: eicosapentaenoic acid (EPA), C22:6 n3: docosahexaenoic acid (DHA), C18:2 n6: linoleic acid, C20:4 n6: arachidonic acid, CA: cholic acid, CDCA: chenodeoxycholic acid, DCA: deoxycholic acid, GCA: glycocholic acid, GDCA: glycodeoxycholic acid, GCDCA: glycochenodeoxycholic acid, n3: omega-3, n6: omega-6, NEFAs: nonesterified fatty acids, PUFAs: polyunsaturated fatty acids, SCFAs: short-chain fatty acids, SFAs: short-chain fatty acids, TCA: taurocholic acid, TDCA: taurodeoxycholic acid, TCDCA: taurochenodeoxycholic acid
Fig. 5
Fig. 5
Relationship between the change in abundance of bacteria and total cholesterol level after interventions with SFAs and PUFAs. Correlation analysis was performed with Pearson correlation, and * indicates P ≤ 0.05. Abbreviations: PUFAs: polyunsaturated fatty acids, SFAs: saturated fatty acids
Fig. 6
Fig. 6
A graphic illustration of the hypothetical mechanisms related to fat quality, gut microbiota, and circulating cholesterol as outlined in the discussion. Replacing SFAs with PUFAs for three days did not affect the levels of bile acids and SCFAs in the circulation. However, gut bacteria may convert cholesterol in the intestine to coprostanol, which is secreted in feces, and hence the circulating levels of cholesterol will decrease. The figure was created with BioRender.com. Abbreviations: PUFAs: polyunsaturated fatty acids, SCFAs: short-chain fatty acids, SFAs: saturated fatty acids

References

    1. Gaundal L, Myhrstad MCW, Leder L, Byfuglien MG, Gjovaag T, Rud I, et al. Beneficial effect on serum cholesterol levels, but not glycaemic regulation, after replacing SFA with PUFA for 3 d: a randomised crossover trial. Br J Nutr. 2021;125(8):915–925. doi: 10.1017/S0007114520003402.
    1. Ulven SM, Leder L, Elind E, Ottestad I, Christensen JJ, Telle-Hansen VH, et al. Exchanging a few commercial, regularly consumed food items with improved fat quality reduces total cholesterol and LDL-cholesterol: a double-blind, randomised controlled trial. Br J Nutr. 2016;116(8):1383–1393. doi: 10.1017/S0007114516003445.
    1. Schwab U, Lauritzen L, Tholstrup T, Haldorssoni T, Riserus U, Uusitupa M, et al. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review. Food Nutr Res. 2014;58:25–45. doi: 10.3402/fnr.v58.25145.
    1. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010;7(3):e1000252. doi: 10.1371/journal.pmed.1000252.
    1. Lovegrove JA. Dietary dilemmas over fats and cardiometabolic risk. Proc Nutr Soc. 2020;79(1):11–21. doi: 10.1017/S0029665119000983.
    1. Hernandez MAG, Canfora EE, Jocken JWE, Blaak EE. The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity. Nutrients. 2019;11(8):1943. doi: 10.3390/nu11081943.
    1. Sharma S, Tripathi P. Gut microbiome and type 2 diabetes: where we are and where to go? J Nutr Biochem. 2019;63:101–108. doi: 10.1016/j.jnutbio.2018.10.003.
    1. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11(10):577–591. doi: 10.1038/nrendo.2015.128.
    1. Allin KH, Nielsen T, Pedersen O. Mechanisms in endocrinology: Gut microbiota in patients with type 2 diabetes mellitus. Eur J Endocrinol. 2015;172(4):R167–R177. doi: 10.1530/EJE-14-0874.
    1. Asnicar F, Berry SE, Valdes AM, Nguyen LH, Piccinno G, Drew DA, et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat Med. 2021;27(2):321–332. doi: 10.1038/s41591-020-01183-8.
    1. Hansen NW, Sams A. The Microbiotic Highway to Health-New Perspective on Food Structure, Gut Microbiota, and Host Inflammation. Nutrients. 2018;10(11):1590. doi: 10.3390/nu10111590.
    1. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010;107(33):14691–14696. doi: 10.1073/pnas.1005963107.
    1. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–563. doi: 10.1038/nature12820.
    1. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. Cell Metab. 2015;22(6):971–982. doi: 10.1016/j.cmet.2015.10.001.
    1. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science (New York, NY) 2011;334(6052):105–108. doi: 10.1126/science.1208344.
    1. Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14. doi: 10.1126/scitranslmed.3000322.
    1. Schoeler M, Caesar R. Dietary lipids, gut microbiota and lipid metabolism. Rev Endocr Metab Disord. 2019;20(4):461–472. doi: 10.1007/s11154-019-09512-0.
    1. Lappi J, Salojärvi J, Kolehmainen M, Mykkänen H, Poutanen K, de Vos WM, et al. Intake of Whole-Grain and Fiber-Rich Rye Bread Versus Refined Wheat Bread Does Not Differentiate Intestinal Microbiota Composition in Finnish Adults with Metabolic Syndrome. J Nutr. 2013;143(5):648–655. doi: 10.3945/jn.112.172668.
    1. Candido FG, Valente FX, Grzeskowiak LM, Moreira APB, Rocha D, Alfenas RCG. Impact of dietary fat on gut microbiota and low-grade systemic inflammation: mechanisms and clinical implications on obesity. Int J Food Sci Nutr. 2018;69(2):125–143. doi: 10.1080/09637486.2017.1343286.
    1. Simoes CD, Maukonen J, Kaprio J, Rissanen A, Pietilainen KH, Saarela M. Habitual dietary intake is associated with stool microbiota composition in monozygotic twins. J Nutr. 2013;143(4):417–423. doi: 10.3945/jn.112.166322.
    1. Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Backhed F. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metab. 2015;22(4):658–668. doi: 10.1016/j.cmet.2015.07.026.
    1. Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012;489(7415):242–249. doi: 10.1038/nature11552.
    1. Kriaa A, Bourgin M, Potiron A, Mkaouar H, Jablaoui A, Gérard P, et al. Microbial impact on cholesterol and bile acid metabolism: current status and future prospects. J Lipid Res. 2019;60(2):323–332. doi: 10.1194/jlr.R088989.
    1. Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ (Clinical research ed) 2018;361:k2179. doi: 10.1136/bmj.k2179.
    1. de Wit N, Derrien M, Bosch-Vermeulen H, Oosterink E, Keshtkar S, Duval C, et al. Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine. Am J Physiol Gastrointest Liver Physiol. 2012;303(5):G589–G599. doi: 10.1152/ajpgi.00488.2011.
    1. Mujico JR, Baccan GC, Gheorghe A, Díaz LE, Marcos A. Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br J Nutr. 2013;110(4):711–720. doi: 10.1017/S0007114512005612.
    1. Noriega BS, Sanchez-Gonzalez MA, Salyakina D, Coffman J. Understanding the Impact of Omega-3 Rich Diet on the Gut Microbiota. Case Rep Med. 2016;2016:3089303. doi: 10.1155/2016/3089303.
    1. Costantini L, Molinari R, Farinon B, Merendino N. Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int J Mol Sci. 2017;18(12):2645. doi: 10.3390/ijms18122645.
    1. Menni C, Zierer J, Pallister T, Jackson MA, Long T, Mohney RP, et al. Omega-3 fatty acids correlate with gut microbiome diversity and production of N-carbamylglutamate in middle aged and elderly women. Sci Rep. 2017;7(1):11079. doi: 10.1038/s41598-017-10382-2.
    1. Selmin OI, Papoutsis AJ, Hazan S, Smith C, Greenfield N, Donovan MG, et al. n-6 High Fat Diet Induces Gut Microbiome Dysbiosis and Colonic Inflammation. Int J Mol Sci. 2021;22(13):6919. doi: 10.3390/ijms22136919.
    1. Kiriyama Y, Nochi H. Physiological Role of Bile Acids Modified by the Gut Microbiome. Microorganisms. 2021;10(1):68. doi: 10.3390/microorganisms10010068.
    1. Callender C, Attaye I, Nieuwdorp M. The Interaction between the Gut Microbiome and Bile Acids in Cardiometabolic Diseases. Metabolites. 2022;12(1):65. doi: 10.3390/metabo12010065.
    1. Casen C, Vebo HC, Sekelja M, Hegge FT, Karlsson MK, Ciemniejewska E, et al. Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment Pharmacol Ther. 2015;42(1):71–83. doi: 10.1111/apt.13236.
    1. Watson H, Mitra S, Croden FC, Taylor M, Wood HM, Perry SL, et al. A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut. 2018;67(11):1974–1983. doi: 10.1136/gutjnl-2017-314968.
    1. Tong A-J, Hu R-K, Wu L-X, Lv X-C, Li X, Zhao L-N, et al. Ganoderma polysaccharide and chitosan synergistically ameliorate lipid metabolic disorders and modulate gut microbiota composition in high fat diet-fed golden hamsters. J Food Biochem. 2020;44(1):e13109. doi: 10.1111/jfbc.13109.
    1. Bordoni A, Amaretti A, Leonardi A, Boschetti E, Danesi F, Matteuzzi D, et al. Cholesterol-lowering probiotics: in vitro selection and in vivo testing of bifidobacteria. Appl Microbiol Biotechnol. 2013;97(18):8273–8281. doi: 10.1007/s00253-013-5088-2.
    1. Wang K, Yu X, Li Y, Guo Y, Ge L, Pu F, et al. Bifidobacterium bifidum TMC3115 Can Characteristically Influence Glucose and Lipid Profile and Intestinal Microbiota in the Middle-Aged and Elderly. Probiotics Antimicrob Proteins. 2019;11(4):1182–1194. doi: 10.1007/s12602-018-9441-8.
    1. Guo Z, Liu XM, Zhang QX, Shen Z, Tian FW, Zhang H, et al. Influence of consumption of probiotics on the plasma lipid profile: A meta-analysis of randomised controlled trials. Nutr Metab Cardiovasc Dis. 2011;21(11):844–850. doi: 10.1016/j.numecd.2011.04.008.
    1. Tindall AM, McLimans CJ, Petersen KS, Kris-Etherton PM, Lamendella R. Walnuts and Vegetable Oils Containing Oleic Acid Differentially Affect the Gut Microbiota and Associations with Cardiovascular Risk Factors: Follow-up of a Randomized, Controlled, Feeding Trial in Adults at Risk for Cardiovascular Disease. J Nutr. 2020;150(4):806–817. doi: 10.1093/jn/nxz289.
    1. Liu Y, Song X, Zhou H, Zhou X, Xia Y, Dong X, et al. Gut Microbiome Associates With Lipid-Lowering Effect of Rosuvastatin in Vivo. Front Microbiol. 2018;9:530. doi: 10.3389/fmicb.2018.00530.
    1. Juste C, Gerard P. Cholesterol-to-Coprostanol Conversion by the Gut Microbiota: What We Know, Suspect, and Ignore. Microorganisms. 2021;9(9):1881. doi: 10.3390/microorganisms9091881.
    1. Sekimoto H, Shimada O, Makanishi M, Nakano T, Katayama O. Interrelationship between serum and fecal sterols. Jpn J Med. 1983;22(1):14–20. doi: 10.2169/internalmedicine1962.22.14.
    1. Wilson JD. The effect of dietary fatty acids on coprostanol excretion by the rat. J Lipid Res. 1961;2(4):7. doi: 10.1016/S0022-2275(20)40478-X.
    1. Kris-Etherton PM, Yu S. Individual fatty acid effects on plasma lipids and lipoproteins: human studies. Am J Clin Nutr. 1997;65(5 Suppl):1628S–S1644. doi: 10.1093/ajcn/65.5.1628S.
    1. Froyen E, Burns-Whitmore B. The Effects of Linoleic Acid Consumption on Lipid Risk Markers for Cardiovascular Disease in Healthy Individuals: A Review of Human Intervention Trials. Nutrients. 2020;12(8):2329. doi: 10.3390/nu12082329.
    1. Kenny DJ, Plichta DR, Shungin D, Koppel N, Hall AB, Fu B, et al. Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level. Cell Host Microbe. 2020;28(2):245–57 e6. doi: 10.1016/j.chom.2020.05.013.
    1. Gérard P, Lepercq P, Leclerc M, Gavini F, Raibaud P, Juste C. Bacteroides sp. Strain D8, the First Cholesterol-Reducing Bacterium Isolated from Human Feces. Appl Environ Microbiol. 2007;73(18):5742–9. doi: 10.1128/AEM.02806-06.
    1. Veiga P, Juste C, Lepercq P, Saunier K, Béguet F, Gérard P. Correlation between faecal microbial community structure and cholesterol-to-coprostanol conversion in the human gut. FEMS Microbiol Lett. 2005;242(1):81–86. doi: 10.1016/j.femsle.2004.10.042.
    1. Antharam VC, McEwen DC, Garrett TJ, Dossey AT, Li EC, Kozlov AN, et al. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection. PLoS ONE. 2016;11(2):e0148824. doi: 10.1371/journal.pone.0148824.
    1. Crowther JS, Drasar BS, Goddard P, Hill MJ, Johnson K. The effect of a chemically defined diet on the faecal flora and faecal steroid concentration. Gut. 1973;14(10):790–793. doi: 10.1136/gut.14.10.790.
    1. Caesar R, Nygren H, Orešič M, Bäckhed F. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism. J Lipid Res. 2016;57(3):474–481. doi: 10.1194/jlr.M065847.
    1. Wolters M, Ahrens J, Romaní-Pérez M, Watkins C, Sanz Y, Benítez-Páez A, et al. Dietary fat, the gut microbiota, and metabolic health – A systematic review conducted within the MyNewGut project. Clin Nutr. 2019;38(6):2504–2520. doi: 10.1016/j.clnu.2018.12.024.
    1. Vacca M, Celano G, Calabrese FM, Portincasa P, Gobbetti M, De Angelis M. The Controversial Role of Human Gut Lachnospiraceae. Microorganisms. 2020;8(4):573. doi: 10.3390/microorganisms8040573.

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