Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet

References

• Hotamisligil GS. Foundations of Immunometabolism and Implications for Metabolic Health and Disease. Immunity. 2017;47(3):406–20. doi:10.1016/j.immuni.2017.08.009.
   PubMed Web of Science ®Google Scholar
• Kondrashova A, Reunanen A, Romanov A, Karvonen A, Viskari H, Vesikari T, Ilonen J, Knip M, Hyöty H. A six‐fold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med. 2005;37(1):67–72. doi:10.1080/07853890410018952.
   PubMed Web of Science ®Google Scholar
• Okin D, Medzhitov R. Evolution of Inflammatory Diseases. Current Biol. 2012;22(17):R733–R40. doi:10.1016/j.cub.2012.07.029.
   PubMed Web of Science ®Google Scholar
• Thorburn Alison N, Macia L, Mackay Charles R. Diet, Metabolites, and “Western-Lifestyle” Inflammatory Diseases. Immunity. 2014;40(6):833–842. doi:10.1016/j.immuni.2014.05.014.
   PubMed Web of Science ®Google Scholar
• Wastyk HC. Determining Causal Relationships Between the Microbiome and Immune System. In: Microbiology and Immunology. Stanford University ProQuest Dissertations Publishing: Stanford University; 2021. p. 213.
   Google Scholar
• Centers for Disease C, Prevention. Centers for Disease Control and Prevention. National Diabetes Statistics Report. 2020;2020:25.
   Google Scholar
• Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018;20(2):12. doi:10.1007/s11906-018-0812-z.
   PubMed Web of Science ®Google Scholar
• Liu CH, Abrams ND, Carrick DM, Chander P, Dwyer J, Hamlet MRJ, Macchiarini F, PrabhuDas M, Shen GL, Tandon P, et al. Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities. Nat Immunol. 2017;18(11):1175–1180. doi:10.1038/ni.3828.
   PubMed Web of Science ®Google Scholar
• Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ, Higginbottom SK, Le A, Cowan TM, Nolan GP, Fischbach MA, et al. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature. 2017;551(7682):648–652. doi:10.1038/nature24661.
   PubMed Web of Science ®Google Scholar
• Marcobal A, Kashyap PC, Nelson TA, Aronov PA, Donia MS, Spormann A, Fischbach MA, Sonnenburg JL. A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice. ISME J. 2013;7(10):1933–1943. doi:10.1038/ismej.2013.89.
   PubMed Web of Science ®Google Scholar
• Sonnenburg ED, Sonnenburg JL. The ancestral and industrialized gut microbiota and implications for human health. Nat Rev Microbiol. 2019;17(6):383–390. doi:10.1038/s41579-019-0191-8.
   PubMed Web of Science ®Google Scholar
• Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228–231. doi:10.1126/science.1179721.
   PubMed Web of Science ®Google Scholar
• Fischbach Michael A, Segre Julia A. Signaling in Host-Associated Microbial Communities. Cell. 2016;164(6):1288–1300. doi:10.1016/j.cell.2016.02.037.
   PubMed Web of Science ®Google Scholar
• Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012;336(6086):1268–1273. doi:10.1126/science.1223490.
   PubMed Web of Science ®Google Scholar
• Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313–323. doi:10.1038/nri2515.
   PubMed Web of Science ®Google Scholar
• Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS. The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic T reg Cell Homeostasis. Science. 2013;341:569–573. doi:10.1126/science.1241165.
   PubMed Web of Science ®Google Scholar
• Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB, Topf M, Gonzalez CG, Van Treuren W, Han S, et al. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021;184(16):4137–53.e14. doi:10.1016/j.cell.2021.06.019.
   PubMed Web of Science ®Google Scholar
• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–563. doi:10.1038/nature12820.
   PubMed Web of Science ®Google Scholar
• Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022;185:3307–28.e19.
   PubMed Web of Science ®Google Scholar
• Vangay P, Johnson AJ, Ward TL, Al-Ghalith GA, Shields-Cutler RR, Hillmann BM, Lucas SK, Beura LK, Thompson EA, Till LM, et al. US Immigration Westernizes the Human Gut Microbiome. Cell. 2018;175(4):962–72.e10. doi:10.1016/j.cell.2018.10.029.
   PubMed Web of Science ®Google Scholar
• Tenorio-Jiménez C, Martínez-Ramírez MJ, Gil Á, Gómez-Llorente C. Effects of Probiotics on Metabolic Syndrome: a Systematic Review of Randomized Clinical Trials. Nutrients. 2020;12(1):E124. doi:10.3390/nu12010124.
   PubMed Web of Science ®Google Scholar
• Didari T, Solki S, Mozaffari S, Nikfar S, Abdollahi M. A systematic review of the safety of probiotics. Expert Opin Drug Saf. 2014;13(2):227–239. doi:10.1517/14740338.2014.872627.
   PubMed Web of Science ®Google Scholar
• Koutsoumanis K, Allende A, Alvarez‐Ordóñez A, Bolton D, Bover‐Cid S, Chemaly M, Davies R, De Cesare A, Hilbert F, Lindqvist R. Update of the list of QPS‐recommended biological agents intentionally added to food or feed as notified to EFSA 12: suitability of taxonomic units notified to EFSA until March 2020. EFS2; 2020:18.
   Google Scholar
• Alberti G, Zimmet P, Shaw J, Grundy S. The IDF consensus worldwide definition of the metabolic syndrome. 2006.
   Google Scholar
• Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermúdez-Humarán LG, Smirnova N, Bergé M, Sulpice T, Lahtinen S, et al. Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. EMBO Mol Med. 2011;3(9):559–572. doi:10.1002/emmm.201100159.
   PubMed Web of Science ®Google Scholar
• Jones ML, Martoni CJ, Parent M, Prakash S. Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-active Lactobacillus reuteri NCIMB 30242 yoghurt formulation in hypercholesterolaemic adults. Br J Nutr. 2012;107(10):1505–1513. doi:10.1017/S0007114511004703.
   PubMed Web of Science ®Google Scholar
• Jones ML, Martoni CJ, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. Eur J Clin Nutr. 2012;66(11):1234–1241. doi:10.1038/ejcn.2012.126.
   PubMed Web of Science ®Google Scholar
• Jones ML, Martoni CJ, Prakash S. Oral Supplementation With Probiotic L. reuteri NCIMB 30242 Increases Mean Circulating 25-Hydroxyvitamin D: a Post Hoc Analysis of a Randomized Controlled Trial. J Clin Endocrinol Metab. 2013;98(7):2944–2951. doi:10.1210/jc.2012-4262.
   PubMed Web of Science ®Google Scholar
• Lyra A, Saarinen M, Putaala H, Olli K, Lahtinen SJ, Ouwehand AC, Madetoja M, Tiihonen K. Bifidobacterium animalis ssp. lactis 420 Protects against Indomethacin-Induced Gastric Permeability in Rats. Gastroenterol Res Pract. 2012;2012:1–9. doi:10.1155/2012/615051.
   Web of Science ®Google Scholar
• Stenman LK, Waget A, Garret C, Klopp P, Burcelin R, Lahtinen S. Potential probiotic Bifidobacterium animalis ssp. Lactis 420 Prevents Weight Gain and Glucose Intolerance in diet-induced Obese Mice Benef Microbes. 2014;5:437–445.
   Google Scholar
• Svedlund J, Sjadin I, Dotevall G. GSRS?A clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33(2):129–134. doi:10.1007/BF01535722.
   PubMed Web of Science ®Google Scholar
• Howard BV, Robbins DC, Sievers ML, Lee ET, Rhoades D, Devereux RB, Cowan LD, Gray RS, Welty TK, Go OT, et al. LDL Cholesterol as a Strong Predictor of Coronary Heart Disease in Diabetic Individuals With Insulin Resistance and Low LDL: the Strong Heart Study. Arterioscler Thromb Vasc Biol. 2000;20(3):830–835. doi:10.1161/01.ATV.20.3.830.
   PubMed Web of Science ®Google Scholar
• Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–846. doi:10.1038/nature05482.
   PubMed Web of Science ®Google Scholar
• Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, Tataranni PA. High Alanine Aminotransferase Is Associated With Decreased Hepatic Insulin Sensitivity and Predicts the Development of Type 2 Diabetes. Diabetes. 2002;51(6):1889–1895. doi:10.2337/diabetes.51.6.1889.
   PubMed Web of Science ®Google Scholar
• Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141–150. doi:10.1016/j.diabres.2014.04.006.
   PubMed Web of Science ®Google Scholar
• Han S, Van Treuren W, Fischer CR, Merrill BD, DeFelice BC, Sanchez JM, Higginbottom SK, Guthrie L, Fall LA, Dodd D, et al. A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature. 2021;595(7867):415–420. doi:10.1038/s41586-021-03707-9.
   PubMed Web of Science ®Google Scholar
• Taf C, Rogero MM, Hassimotto NMA, Lajolo FM. The Two-Way Polyphenols-Microbiota Interactions and Their Effects on Obesity and Related Metabolic Diseases. Front Nutr. 2019;6:188. doi:10.3389/fnut.2019.00188.
   PubMed Web of Science ®Google Scholar
• Neurath MF. Host–microbiota interactions in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17(2):76–77. doi:10.1038/s41575-019-0248-1.
   PubMed Web of Science ®Google Scholar
• Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, et al. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013;110(22):9066–9071. doi:10.1073/pnas.1219451110.
   PubMed Web of Science ®Google Scholar
• Plovier H, Everard A, Druart C, Depommier C, Van Hul M, Geurts L, Chilloux J, Ottman N, Duparc T, Lichtenstein L, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–113. doi:10.1038/nm.4236.
   PubMed Web of Science ®Google Scholar
• Blais Lecours P, Marsolais D, Cormier Y, Berberi M, Haché C, Bourdages R, Duchaine C. Increased Prevalence of Methanosphaera stadtmanae in Inflammatory Bowel Diseases. PLoS ONE. 2014;9(2):e87734. doi:10.1371/journal.pone.0087734.
   PubMed Web of Science ®Google Scholar
• Edwards PT, Kashyap PC, Preidis GA. Microbiota on biotics: probiotics, prebiotics, and synbiotics to optimize growth and metabolism. Am J Physiol Gastrointest Liver Physiol. 2020;319(3):G382–g90. doi:10.1152/ajpgi.00028.2020.
   PubMed Web of Science ®Google Scholar
• Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med. 2019;25(5):716–729. doi:10.1038/s41591-019-0439-x.
   PubMed Web of Science ®Google Scholar
• Canani RB, Cirillo P, Terrin G, Cesarano L, Spagnuolo MI, Vincenzo AD, Albano F, Passariello A, Marco GD, Manguso F, et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ. 2007;335(7615):340. doi:10.1136/bmj.39272.581736.55.
   PubMed Web of Science ®Google Scholar
• Gao XW, Mubasher M, Fang CY, Reifer C, Miller LE. Dose-response efficacy of a proprietary probiotic formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for antibiotic-associated diarrhea and Clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010;105(7):1636–1641. doi:10.1038/ajg.2010.11.
   PubMed Web of Science ®Google Scholar
• Kruis W, Fric P, Pokrotnieks J, Lukás M, Fixa B, Kascák M, Kamm MA, Weismueller J, Beglinger C, Stolte M. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut. 2004;53(11):1617–1623. doi:10.1136/gut.2003.037747.
   PubMed Web of Science ®Google Scholar
• Ruszczyński M, Radzikowski A, Szajewska H. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol Ther. 2008;28(1):154–161. doi:10.1111/j.1365-2036.2008.03714.x.
   PubMed Web of Science ®Google Scholar
• Ardeshirlarijani E, Tabatabaei-Malazy O, Mohseni S, Qorbani M, Larijani B, Baradar Jalili R. Effect of probiotics supplementation on glucose and oxidative stress in type 2 diabetes mellitus: a meta-analysis of randomized trials. Daru. 2019;27(2):827–837. doi:10.1007/s40199-019-00302-2.
   PubMed Web of Science ®Google Scholar
• Borgeraas H, Johnson LK, Skattebu J, Hertel JK, Hjelmesaeth J. Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials. Obes Rev. 2018;19(2):219–232. doi:10.1111/obr.12626.
   PubMed Web of Science ®Google Scholar
• Dong Y, Xu M, Chen L, Bhochhibhoya A. Probiotic Foods and Supplements Interventions for Metabolic Syndromes: a Systematic Review and Meta-Analysis of Recent Clinical Trials. Ann Nutr Metab. 2019;74(3):224–241. doi:10.1159/000499028.
   PubMed Web of Science ®Google Scholar
• Ruan Y, Sun J, He J, Chen F, Chen R, Chen H. Effect of Probiotics on Glycemic Control: a Systematic Review and Meta-Analysis of Randomized, Controlled Trials. PLoS ONE. 2015;10(7):e0132121. doi:10.1371/journal.pone.0132121.
   PubMed Web of Science ®Google Scholar
• Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, Zur M, Regev-Lehavi D, Ben-Zeev Brik R, Federici S, et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018;174(6):1406–23.e16. doi:10.1016/j.cell.2018.08.047.
   PubMed Web of Science ®Google Scholar
• Kothari D, Patel S, Kim SK. Probiotic supplements might not be universally-effective and safe: a review. Biomed Pharmacother. 2019;111:537–547. doi:10.1016/j.biopha.2018.12.104.
   PubMed Web of Science ®Google Scholar
• Shapiro H, Suez J, Elinav E. Personalized microbiome-based approaches to metabolic syndrome management and prevention. J Diabetes. 2017;9(3):226–236. doi:10.1111/1753-0407.12501.
   PubMed Web of Science ®Google Scholar
• Lambert GW, Eisenhofer G, Cox HS, Horne M, Kalff V, Kelly M, Jennings GL, Esler MD. Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity. Life Sci. 1991;49(15):1061–1072. doi:10.1016/0024-3205(91)90593-Z.
   PubMed Web of Science ®Google Scholar
• Wang Y, Li N, Yang -J-J, Zhao D-M, Chen B, Zhang G-Q, Chen S, Cao R-F, Yu H, Zhao C-Y, et al. Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder. Pharmacoll Res. 2020;157:104784. doi:10.1016/j.phrs.2020.104784.
   PubMed Web of Science ®Google Scholar
• Zhao D, Yuan B, Carry E, Pasinetti GM, Ho L, Faith J, Mogno I, Simon J, Wu Q. Development and validation of an ultra-high performance liquid chromatography/triple quadrupole mass spectrometry method for analyzing microbial-derived grape polyphenol metabolites. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1099:34–45. doi:10.1016/j.jchromb.2018.09.014.
   PubMed Web of Science ®Google Scholar
• Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, Almeida M, Quinquis B, Levenez F, Galleron N, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500(7464):585–588. doi:10.1038/nature12480.
   PubMed Web of Science ®Google Scholar
• Korem T, Zeevi D, Zmora N, Weissbrod O, Bar N, Lotan-Pompan M, Avnit-Sagi T, Kosower N, Malka G, Rein M, et al. Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses. Cell Metab. 2017;25(6):1243–1253.e5. doi:10.1016/j.cmet.2017.05.002.
   PubMed Web of Science ®Google Scholar
• Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, Hallen A, Martens E, Björck I, Bäckhed F, 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.
   PubMed Web of Science ®Google Scholar
• Martínez I, Lattimer JM, Hubach KL, Case JA, Yang J, Weber CG, Louk JA, Rose DJ, Kyureghian G, Peterson DA, et al. Gut microbiome composition is linked to whole grain-induced immunological improvements. ISME J. 2013;7(2):269–280. doi:10.1038/ismej.2012.104.
   PubMed Web of Science ®Google Scholar
• Tanes C, Bittinger K, Gao Y, Friedman ES, Nessel L, Paladhi UR, Chau L, Panfen E, Fischbach MA, Braun J, et al. Role of dietary fiber in the recovery of the human gut microbiome and its metabolome. Cell Host Microbe. 2021;29(3):394–407.e5. doi:10.1016/j.chom.2020.12.012.
   PubMed Web of Science ®Google Scholar
• Sonnenburg JL, Bäckhed F. Diet–microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56–64. doi:10.1038/nature18846.
   PubMed Web of Science ®Google Scholar
• Kristensen NB, Bryrup T, Allin KH, Nielsen T, Hansen TH, Pedersen O. Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials. Genome Med. 2016;8(1):52. doi:10.1186/s13073-016-0300-5.
   PubMed Web of Science ®Google Scholar
• Wieërs G, Belkhir L, Enaud R, Leclercq S, Philippart de Foy JM, Dequenne I, de Timary P, Cani PD. How Probiotics Affect the Microbiota. Front Cell Infect Microbiol. 2019;9:454. doi:10.3389/fcimb.2019.00454.
   PubMed Web of Science ®Google Scholar
• Xu Y, Wang N, Tan HY, Li S, Zhang C, Feng Y. Function of Akkermansia muciniphila in Obesity: interactions With Lipid Metabolism, Immune Response and Gut Systems. Front Microbiol. 2020;11:219. doi:10.3389/fmicb.2020.00219.
   PubMed Web of Science ®Google Scholar
• Si J, Kang H, You HJ, Ko G. Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium. Gut Microbes. 2022;14(1):2078619. doi:10.1080/19490976.2022.2078619.
   PubMed Web of Science ®Google Scholar
• Stanhope KL. Sugar consumption, metabolic disease and obesity: the state of the controversy. Crit Rev Clin Lab Sci. 2016;53(1):52–67. doi:10.3109/10408363.2015.1084990.
   PubMed Web of Science ®Google Scholar
• Kimoto-Nira H, Suzuki C, Sasaki K, Kobayashi M, Mizumachi K. Survival of a Lactococcus lactis strain varies with its carbohydrate preference under in vitro conditions simulated gastrointestinal tract. Int J Food Microbiol. 2010;143(3):226–229. doi:10.1016/j.ijfoodmicro.2010.07.033.
   PubMed Web of Science ®Google Scholar
• Kassaian N, Feizi A, Aminorroaya A, Amini M. Probiotic and synbiotic supplementation could improve metabolic syndrome in prediabetic adults: a randomized controlled trial. Diabetes Metab Syndr. 2019;13(5):2991–2996. doi:10.1016/j.dsx.2018.07.016.
   PubMed Web of Science ®Google Scholar
• Johansson ML, Molin G, Jeppsson B, Nobaek S, Ahrné S, Bengmark S. Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Appl Environ Microbiol. 1993;59(1):15–20. doi:10.1128/aem.59.1.15-20.1993.
   PubMed Web of Science ®Google Scholar
• Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, Nauta A, Scott K, Stahl B, van Harsselaar J, et al. Short chain fatty acids in human gut and metabolic health. Benef Microbes. 2020;11(5):411–455. doi:10.3920/BM2020.0057.
   PubMed Web of Science ®Google Scholar
• Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, Ben-Yacov O, Lador D, Avnit-Sagi T, Lotan-Pompan M, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015;163(5):1079–1094. doi:10.1016/j.cell.2015.11.001.
   PubMed Web of Science ®Google Scholar
• Winham DM, Hutchins AM. Perceptions of flatulence from bean consumption among adults in 3 feeding studies. Nutr J. 2011;10(1):128. doi:10.1186/1475-2891-10-128.
   PubMedGoogle Scholar
• Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385–396. doi:10.2307/2136404.
   PubMed Web of Science ®Google Scholar
• Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–1395. doi:10.1249/01.MSS.0000078924.61453.FB.
   PubMed Web of Science ®Google Scholar
• Gilbert JA, Jansson JK, Knight R. The Earth Microbiome project: successes and aspirations. BMC Biol. 2014;12(1):69. doi:10.1186/s12915-014-0069-1.
   PubMedGoogle Scholar
• Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Peña AG, Goodrich JK, Gordon JI, et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods. 2010;7(5):335–336. doi:10.1038/nmeth.f.303.
   PubMed Web of Science ®Google Scholar
• Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–583. doi:10.1038/nmeth.3869.
   PubMed Web of Science ®Google Scholar
• Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci. 2009;106(10):3698–3703. doi:10.1073/pnas.0812874106.
   PubMed Web of Science ®Google Scholar
• Tsugawa H, Cajka T, Kind T, Ma Y, Higgins B, Ikeda K, Kanazawa M, VanderGheynst J, Fiehn O, Arita M, et al. MS-DIAL: data-independent MS/MS deconvolution for comprehensive metabolome analysis. Nat Methods. 2015;12(6):523–526. doi:10.1038/nmeth.3393.
   PubMed Web of Science ®Google Scholar
• Chen EZ, Li H. A two-part mixed-effects model for analyzing longitudinal microbiome compositional data. Bioinformatics. 2016;32(17):2611–2617. doi:10.1093/bioinformatics/btw308.
   PubMed Web of Science ®Google Scholar