Metagenomic Profiling of Gut Microbiota in Response to High-Fiber Dietary Interventions

Authors

  • Sylvie Bakker Department of Bioinformatics and Computational Biology, Baltic Institute of Biomedical Research, Sweden Author
  • Eszter Saez-Bermudez Department of Biomedical and Health Sciences, Iberian University Center for Biotechnology, Spain Author
  • Wolfgang Bianchi Department of Bioinformatics and Computational Biology, Iberian University Center for Biotechnology, Spain Author

DOI:

https://doi.org/10.5281/zenodo.22687576

Keywords:

gut microbiota, shotgun metagenomics, dietary fiber, short-chain fatty acids, Faecalibacterium prausnitzii, microbiome-diet interaction

Abstract

Fiber intake across most industrialised populations sits well below the level associated with a resilient,
fermentation-competent gut microbiota, yet the strain-level and functional consequences of raising fiber intake in
free-living adults are still incompletely mapped. We conducted an 8-week randomised, controlled, parallel-arm
feeding trial in 42 healthy adults comparing a high-fiber diet (35 g fermentable fiber per day, delivered through
whole grains, legumes and inulin-enriched foods) against a habitual-diet control, with stool shotgun metagenomic
sequencing and faecal short-chain fatty acid (SCFA) quantification performed at baseline and week 8. Thirty-nine
participants (19 intervention, 20 control) completed the protocol. Shannon diversity rose from 3.11 to 3.44 in the
intervention arm (paired t-test, P<0.001) with no change in controls (P=0.41), and Bray-Curtis PERMANOVA
showed significant within-arm compositional shift over time in the intervention group only (R2=0.081, P=0.002).
Bifidobacterium, Faecalibacterium prausnitzii, Roseburia spp. and Ruminococcus bromii all increased significantly
in relative abundance (log2 fold changes of 2.29, 1.60, 1.94 and 1.71 respectively, all q<0.01), while the
Bacteroides fragilis group declined modestly. Functional profiling showed coordinated enrichment of glycoside
hydrolase families GH13 and GH43 and of starch and sucrose degradation pathways, and faecal butyrate
concentration increased from 12.4 to 18.7 micromol per gram dry weight (P<0.001), with smaller but significant
increases in propionate. No comparable shifts occurred in the control arm. These results provide strain- and
pathway-resolved evidence that a sustained, moderate increase in dietary fiber reproducibly favours a
saccharolytic, butyrogenic community configuration in adults without pre-existing gastrointestinal disease, and
they identify a compact set of taxa and gene families that could serve as response biomarkers in future
fiber-intervention trials.

References

Sonnenburg JL, Backhed F (2016) Diet-microbiota interactions as moderators of human metabolism. Nature 535(7610):56-64. https://doi.org/10.1038/nature18846

Deehan EC, Yang C, Perez-Munoz ME, Nguyen NK, Cheng CC, Triador L, Zhang Z, Bakal JA, Walter J (2020) Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host & Microbe 27(3):389-404. https://doi.org/10.1016/j.chom.2020.01.006

Sonnenburg ED, Sonnenburg JL (2014) Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metabolism 20(5):779-786. https://doi.org/10.1016/j.cmet.2014.07.003

Makki K, Deehan EC, Walter J, Backhed F (2018) The impact of dietary fiber on gut microbiota in host health and disease. Cell Host & Microbe 23(6):705-715. https://doi.org/10.1016/j.chom.2018.05.012

O'Keefe SJ, Li JV, Lahti L, Ou J, Carbonero F, Mohammed K, Posma JM, Kinross J, Wahl E, Ruder E, Vipperla K (2015) Fat, fibre and cancer risk in African Americans and rural Africans. Nature Communications 6:6342. https://doi.org/10.1038/ncomms7342

Zmora N, Suez J, Elinav E (2019) You are what you eat: diet, health and the gut microbiota. Nature Reviews Gastroenterology & Hepatology 16(1):35-56. https://doi.org/10.1038/s41575-018-0061-2

Cronin P, Joyce SA, O'Toole PW, O'Connor EM (2021) Dietary fibre modulates the gut microbiota. Nutrients 13(5):1655. https://doi.org/10.3390/nu13051655

So D, Whelan K, Rossi M, Morrison M, Holtmann G, Kelly JT, Shanahan ER, Staudacher HM, Campbell KL (2018) Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis. American Journal of Clinical Nutrition 107(6):965-983. https://doi.org/10.1093/ajcn/nqy041

Holscher HD (2017) Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes 8(2):172-184. https://doi.org/10.1080/19490976.2017.1290756

Deehan EC, Duar RM, Armet AM, Perez-Munoz ME, Jin M, Walter J (2017) Modulation of the gastrointestinal microbiome with nondigestible fermentable carbohydrates to improve human health. Microbiology Spectrum 5(5). https://doi.org/10.1128/microbiolspec.BAD-0019-2017

Beghini F, McIver LJ, Blanco-Miguez A, Dubois L, Asnicar F, Maharjan S, Mailyan A, Manghi P, Scholz M, Thomas AM, Valles-Colomer M (2021) Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. eLife 10:e65088. https://doi.org/10.7554/eLife.65088

Mallick H, Rahnavard A, McIver LJ, Ma S, Zhang Y, Nguyen LH, Tickle TL, Weingart G, Ren B, Schwager EH, Chatterjee S (2021) Multivariable association discovery in population-scale meta-omics studies. PLOS Computational Biology 17(11):e1009442. https://doi.org/10.1371/journal.pcbi.1009442

Louis P, Flint HJ (2017) Formation of propionate and butyrate by the human colonic microbiota. Environmental Microbiology 19(1):29-41. https://doi.org/10.1111/1462-2920.13589

Miquel S, Martin R, Rossi O, Bermudez-Humaran LG, Chatel JM, Sokol H, Thomas M, Wells JM, Langella P (2013) Faecalibacterium prausnitzii and human intestinal health. Current Opinion in Microbiology 16(3):255-261. https://doi.org/10.1016/j.mib.2013.06.003

Tamanai-Shacoori Z, Smida I, Bousarghin L, Loreal O, Meuric V, Fong SB, Bonnaure-Mallet M, Jolivet-Gougeon A (2017) Roseburia spp.: a marker of health? Future Microbiology 12(2):157-170. https://doi.org/10.2217/fmb-2016-0130

Ze X, Duncan SH, Louis P, Flint HJ (2012) Ruminococcus bromii is a keystone species for the degradation of resistant starch in the human colon. ISME Journal 6(8):1535-1543. https://doi.org/10.1038/ismej.2012.4

Falony G, Joossens M, Vieira-Silva S, Wang J, Darzi Y, Faust K, Kurilshikov A, Bonder MJ, Valles-Colomer M, Vandeputte D, Tito RY (2016) Population-level analysis of gut microbiome variation. Science 352(6285):560-564. https://doi.org/10.1126/science.aad3503

Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T, Mujagic Z, Vila AV, Falony G, Vieira-Silva S, Wang J (2016) Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352(6285):565-569. https://doi.org/10.1126/science.aad3369

Maier TV, Lucio M, Lee LH, VerBerkmoes NC, Brislawn CJ, Bernhardt J, Lamendella R, McDermott JE, Bergeron N, Heinzmann SS, Morton JT (2017) Impact of dietary resistant starch on the human gut microbiome, metaproteome, and metabolome. mBio 8(5):e01343-17. https://doi.org/10.1128/mBio.01343-17

Chung WS, Walker AW, Louis P, Parkhill J, Vermeiren J, Bosscher D, Duncan SH, Flint HJ (2016) Modulation of the human gut microbiota by dietary fibres occurs at the species level. BMC Biology 14:3. https://doi.org/10.1186/s12915-015-0224-3

Martinez I, Kim J, Duffy PR, Schlegel VL, Walter J (2010) Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PLOS ONE 5(11):e15046. https://doi.org/10.1371/journal.pone.0015046

Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JA, Brandsma E, Marczynska J, Imhann F, Weersma RK, Franke L (2015) The gut microbiome contributes to a substantial proportion of the variation in blood lipids. Circulation Research 117(9):817-824. https://doi.org/10.1161/CIRCRESAHA.115.306807

Weickert MO, Pfeiffer AF (2018) Impact of dietary fiber consumption on insulin resistance and the prevention of type 2 diabetes. Journal of Nutrition 148(1):7-12. https://doi.org/10.1093/jn/nxx008

Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L (2019) Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. The Lancet 393(10170):434-445. https://doi.org/10.1016/S0140-6736(18)31809-9

Fuller S, Beck E, Salman H, Tapsell L (2016) New horizons for the study of dietary fiber and health: a review. Plant Foods for Human Nutrition 71(1):1-12. https://doi.org/10.1007/s11130-016-0529-6

Barber TM, Kabisch S, Pfeiffer AFH, Weickert MO (2020) The health benefits of dietary fibre. Nutrients 12(10):3209. https://doi.org/10.3390/nu12103209

Byrne CS, Chambers ES, Morrison DJ, Frost G (2015) The role of short chain fatty acids in appetite regulation and energy homeostasis. International Journal of Obesity 39(9):1331-1338. https://doi.org/10.1038/ijo.2015.84

Parada Venegas D, De la Fuente MK, Landskron G, Gonzalez MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in Immunology 10:277. https://doi.org/10.3389/fimmu.2019.00277

Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341(6145):569-573. https://doi.org/10.1126/science.1241165

Cummings JH, Macfarlane GT (1997) Role of intestinal bacteria in nutrient metabolism. Journal of Parenteral and Enteral Nutrition 21(6):357-365. https://doi.org/10.1177/0148607197021006357

Roager HM, Vogt JK, Kristensen M, Hansen LBS, Ibrugger S, Maerkedahl RB, Bahl MI, Lind MV, Nielsen RL, Frokiaer H, Gobel RJ (2019) Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome. Gut 68(1):83-93. https://doi.org/10.1136/gutjnl-2017-314786

Klinder A, Shen Q, Heppel S, Lovegrove JA, Rowland I, Tuohy KM (2016) Impact of increasing fruit and vegetables and flavonoid intake on the human gut microbiota. Food & Function 7(4):1788-1796. https://doi.org/10.1039/C5FO01096A

Vandeputte D, Falony G, Vieira-Silva S, Tito RY, Joossens M, Raes J (2016) Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65(1):57-62. https://doi.org/10.1136/gutjnl-2015-309618

Nagpal R, Shively CA, Register TC, Craft S, Yadav H (2019) Gut microbiome-Mediterranean diet interactions in improving host health. F1000Research 8:699. https://doi.org/10.12688/f1000research.18992.1

Sender R, Fuchs S, Milo R (2016) Revised estimates for the number of human and bacteria cells in the body. PLOS Biology 14(8):e1002533. https://doi.org/10.1371/journal.pbio.1002533

Kelly TN, Bazzano LA, Ajami NJ, He H, Zhao J, Petrosino JF, Correa A, He J (2016) Gut microbiome associates with lifetime cardiovascular disease risk profile among Bogalusa Heart Study participants. Circulation Research 119(8):956-964. https://doi.org/10.1161/CIRCRESAHA.116.309219

Sonnenburg JL, Sonnenburg ED (2019) Vulnerability of the industrialized microbiota. Science 366(6464):eaaw9255. https://doi.org/10.1126/science.aaw9255

Ianiro G, Punkova A, Segata N, Cammarota G (2022) Gut microbiome dysbiosis and human diseases: an evolving concept. Nature Reviews Microbiology 20(9):515-530. https://doi.org/10.1038/s41579-022-00714-7

Portincasa P, Bonfrate L, Vacca M, De Angelis M, Farella I, Lanza E, Khalil M, Wang DQ, Sperandio M, Di Ciaula A (2022) Gut microbiota and short chain fatty acids: implications in glucose homeostasis. International Journal of Molecular Sciences 23(3):1105. https://doi.org/10.3390/ijms23031105

Ercolini D, Fogliano V (2018) Food design to feed the human gut microbiota. Journal of Agricultural and Food Chemistry 66(15):3754-3758. https://doi.org/10.1021/acs.jafc.8b00456

Verhoog S, Taneri PE, Roa Diaz ZM, Marques-Vidal P, Troup JP, Bally L, Franco OH, Glisic M, Muka T (2019) Dietary factors and modulation of bacteria strains of Akkermansia muciniphila and Faecalibacterium prausnitzii: a systematic review. Nutrients 11(7):1565. https://doi.org/10.3390/nu11071565

Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, Alexander H, Alm EJ, Arumugam M, Asnicar F, Bai Y (2019) Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nature Biotechnology 37(8):852-857. https://doi.org/10.1038/s41587-019-0209-9

Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R (2008) Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57(6):1470-1481. https://doi.org/10.2337/db07-1403

Frank DN, St Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. PNAS 104(34):13780-13785. https://doi.org/10.1073/pnas.0706625104

Flint HJ, Scott KP, Duncan SH, Louis P, Forano E (2012) Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3(4):289-306. https://doi.org/10.4161/gmic.19897

Rios-Covian D, Ruas-Madiedo P, Margolles A, Gueimonde M, de los Reyes-Gavilan CG, Salazar N (2016) Intestinal short chain fatty acids and their link with diet and human health. Frontiers in Microbiology 7:185. https://doi.org/10.3389/fmicb.2016.00185

Berry SE (2019) Nutritional intervention studies and the gut microbiome: challenges and opportunities. Proceedings of the Nutrition Society 78(3):315-322. https://doi.org/10.1017/S0029665118002856

Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE (2007) Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Applied and Environmental Microbiology 73(4):1073-1078. https://doi.org/10.1128/AEM.02340-06

Deehan EC, Zhang Z, Riva A, Armet AM, Perez-Munoz ME, Nguyen NK, Krysa JA, Seethaler B, Zhao YM, Cole J, Li F (2022) Elucidating the role of the gut microbiota in the physiological effects of dietary fiber. Microbiome 10:77. https://doi.org/10.1186/s40168-022-01248-5

Simpson HL, Campbell BJ (2015) Review article: dietary fibre-microbiota interactions. Alimentary Pharmacology & Therapeutics 42(2):158-179. https://doi.org/10.1111/apt.13248

Karl JP, Meydani M, Barnett JB, Vanegas SM, Barger K, Fu X, Goldin B, Kane A, Rasmussen H, Vangay P, Knights D (2017) Fecal concentrations of bacterially derived vitamin K forms are associated with gut microbiota composition in men. American Journal of Clinical Nutrition 106(4):1052-1061. https://doi.org/10.3945/ajcn.117.155424

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Published

2023-06-28