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Microbiome that reside in the human gut are key contributors to host metabolism and are considered potential sources of novel therapeutics in metabolic disorders. This review discusses the role of gut microbiome in the pathogenesis of obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease and cardiovascular disease. Gut microbiome remains quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understanding these changes is important to predict diseases and develop therapies. In gut heamostasis, Gut microbiome converts high fibres intake into short-chain fatty acids like butyrate, propionate and acetate which normalize intestinal permeability and alter de novo lipogenesis and gluconeogenesis through reduction of free fatty acid production by visceral adipose tissue. This effect contributes to reduce food intake and to improve glucose metabolism. Propionate can also bind to G protein coupled receptors (GPR)-43 expressed on lymphocytes in order to maintain appropriate immune defence. Butyrate activates peroxisome proliferator-activated receptor-γ (PPAR-γ) leading to beta-oxidation and oxygen consumption, a phenomenon contributing to maintain anaerobic condition in the gut lumen. In contrast, diets most especially western diet consisting among others of high fat and high salt content has been reported to cause gut dysbiosis. This alteration of gut microbiome result to chronic bacterial translocation and increased intestinal permeability that can drive a systemic inflammation leading to macrophage influx into visceral adipose tissue, activation of hepatic kuffer cells and insulin resistance in type 2 diabetes. This effect contributes to lower mucus thickness, decrease butyrate and propionate producing bacteria, L-cells secrete less gut peptides, lack of PPAR-γ activation lead to higher oxygen available for the microbiome at the proximity of the mucosa and increases the proliferation of Enterobacteriaceae with commensurate increase in opportunistic pathogens. However, Gut microbiome are major biomarker for early prognosis of diabetes and other metabolic disorders.
Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482:179–185.
Khan MT, Nieuwdorp M, Backhed F. Microbial modulation of insulin sensitivity. Cell Metabolism. 2014;20:753–760.
Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535:376–381.
Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer S. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013;58: 120–127.
Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH. Hepatology. 2013;57:601–609.
Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33:570–580.
Tilg H, Adolph TE, Gerner RR, Moschen AR. The intestinal microbiota in colorectal cancer. Cancer Cell. 2018;33:954–964.
Li W, Andrew D. Factors influencing the gut microbiota, inflammation and type 2 diabetes. The Journal of Nutrition. 2017;147(7):1468S–1475S.
Zhang C, Yin A, Li H, Wang R, Wu G, Shen J, Zhang M, Wang L, Hou Y, Ouyang. Dietary modulation of gut microbiota contributes to alleviation of both genetic and simple obesity in children. EbioMedicine. 2015;2:968–984.
Rothe M, Blaut M. Evolution of the gut microbiota and the influence of diet. Benefit Microbes. 2013;4:31–37.
Compare D, Rocco A, Sanduzzi Zamparelli M, Nardone G. The gut bacteria-driven obesity development. Digestive Disease. 2016;34:221–229.
Vazquez G, Duval S, Jacobs DR, Silventoinen K. Comparison of body mass index, waist circumference and waist/hip ratio in predicting incident diabetes: A meta-analysis. Epidemiology Review. 2007;115:2007–2029.
Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334: 105–108.
Wander PL, Boyko EJ, Leonetti DL, McNeely MJ, Kahn SE, Fujimoto WY. Change in visceral adiposity independently predicts a greater risk of developing type 2 diabetes over 10 years in Japanese Americans. Diabetes Care. 2013;36:289–293.
Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Procedure. Natural Academic Science USA. 2013;1(10):9066–9071.
Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME Journal. 2017;6:320–329.
Sharma R, Prajapati PK. Rising risk of type 2 diabetes among inhabitants of Jamnagar, Gujarat: A cross-sectional survey. An International Quarterly Journal of Research in Ayurveda. 2015;36(1):10–17.
Alexandra P, Christopher Y, Jayne SD. The influence of the microbiome on type 1 diabetes. Journal of Immunology. 2017;198:590–595.
Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Revised Endocrine Metabolism Disorder. 2015;16(1):55-65.
Karovonen M, Tuomilehto J, Libman I. A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. World Health Organization DiaMond Group. Diabetologia. 1993;36:883-892.
Holt RIG. Diagnosis, epidemiology and pathogenesis of diabetes mellitus: An update for psychiatrists. British Journal Psychiatry. 2004;184:s55-s63.
Kaprio J, Tuomilehto J, Koskenvuo M, Romanov K, Eriksson J, Stengard J. Concordance for type 1(insulin-dependent) and Type (non-insulin-dependent) diabetes mellitus in a population base chort of twice in Finland. Diabetologia. 1992;35:1060-1067.
Onkamo P, Vaananen S, Karvonen M. Worldwide increase in incidence of type 1 diabetes--the analysis of the data on published incidence trends. Diabetologia. 1999;42:1395-1403.
Kyvik KO, Nystrom L, Gorus F. The epidemiology of type 1 diabetes mellitus is not the same in young adults as in children. Diabetologia. 2004;47:377-384.
Dorman JS, LaPorte RE, Songer TJ. Epidemiology of type 1 diabetes, in type 1 diabetes: Etiology and treatment. Mark A. Sperling. Humana Press. 2003;3-22.
Fox CS, Coady S, Sorlie PD, Levy D, Meigs JB, D'Agostino, RBS, Wilson P, Savage PJ. Trends in cardiovascular complications of diabetes. JAMA. 2004;292(20):2495–2499.
Chatenoud L. World diabetes day: Perspectives on immunotherapy of type 1 diabetes. European Journal of Immunology. 2015;45(11):2968–2970.
Osuji CU, Nzerem BA, Dioka CE, Meludu SC, Onwubuya EI. Prevaleence of diabetes mellitus in a group of women attending “August meeting” at Naze South East Nigeria. Journal of Diabetes Mellitus; 2012.
Jakobsson HE, Abrahamsson TR, Jenmalm MC, Harris K, Quince C, Jernberg. Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut. 2014;4:559–556.
Bokulich NA, Chung J, Battaglia T, Henderson N, Jay M, Li H. Antibiotics, birth mode and diet shape microbiome maturation during early life. Science Translation Medicine. 2016;8(343):343-382.
Schloissnig S, Arumugam M, Sunagawa S, Mitreva M, Tap J, Zhu A. Genomic variation landscape of the human gut microbiome. Nature. 2013;493(7430):45–50.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484): 559–563.
Falony G. Population-level analysis of gut microbiome variation. Science. 2016; 352(6285):560–564.
Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Manneras-Holm L. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nature Medicine. 2017;223(7): 850–858.
Freedberg DE, Toussaint NC, Chen SP, Ratner AJ, Whittier S, Wang TC. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome: A crossover trial. Gastroenterology. 2015;149(4):883–885.
Centers for Disease Control; 2017.
Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI. Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Natural Medicine. 2016;250–253.
Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life implications for health outcomes. Natural Medicine. 2016;22:713–722.
Kulas T, Bursac D, Zegarac Z, Planinic-Rados G, Hrgovic Z. New views on cesarean section, its possible complications and long-term consequences for children's health. Medical Arch. 2013;67:460–463.
Li H, Ye R, Pei L, Ren A, Zheng X, Liu J. Caesarean delivery, caesare delivery on maternal request and childhood overweight: A Chinese birth cohort study of 181 380 children. Pediatric Obese. 2014;9:10-16.
Portela DS, Vieira TO, Matos SM, de Oliveira NF, Vieira GO. Maternal obesity, environmental factors, cesarean delivery and breastfeeding as determinants of overweight and obesity in children: Results from a cohort. BMC Pregnancy Childbirth. 2015;15:94.
Kuhle S, Tong OS, Woolcott CG. Association between caesarean section an childhood obesity: A systematic review and meta-analysis. Obese Review. 2015;16: 295–303.
Pei Z, Heinrich J, Fuertes E, Flexeder C, Hoffmann B, Lehmann I, Schaaf B, von Berg A, Koletzko S. Influences of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus Air Pollution and Genetics (LISAplus) Study Group. Cesarean delivery and risk of childhood obesity. Journal Pediatrics. 2014;164:1068– 1073.
Fitzstevens JL, Smith KC, Hagadorn JI, Caimano MJ, Matson AP, Brownell EA. Systematic review of the human milk microbiota. Nutritional Clinical Practice; 2016.
Boix-Amorós A, Collado MC, Mira A. Relationship between milk microbiota bacterial load, macronutrients and human cells during lactation. Frontier Microbiology. 2016;492.
Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight a mode of delivery. American Journal Clinical Nutrition. 2012;96:544–551.
Obermajer T, Pogacic T. Commentary: Relationship between milk microbiota, bacterial load, macronutrients and human cells during lactation. Frontier Microbiology. 2016;7:1281.
Panagos P, Matthan N, Sen S. Effects of maternal obesity on breast milk composition and infant growth. FASEB Journal. 2014;28(1):247.
Panagos PG, Vishwanathan R, Penfield-Cyr A, Matthan NR, Shivappa N, Wirth MD, Hebert JR, Sen S. Breast milk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. Journal Perinatology. 2016;36:284–290.
Hanson LA, Soderstrom T. Human milk: Defense against infection. Progressive Clinical Biology Resources. 1981;61:147–159.
Hanson LA, Ahlstedt S, Andersson B, Cruz JR, Dahlgren U, Fallstrom SP, Porras O, Svanborg Eden C, Soderstrom T, Wettergren B. The immune response of theammary gland and its significance for the neonate. Annual Allergy. 1984;53:576–582.
Borch-Johnsen K, Joner G, Mandrup-Poulsen T. Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis. Lancet. 1984;2:1083-1086.
Kolb H, Pozzilli P. Cow's milk and type 1 diabetes: The gut immune system deserves attention. Immunology Today. 1999;20:108-110.
Dahlquist G. The aetiology of type 1 diabetes: An epidemiological perspective. Acta Paediatrica. 1998;425:5-10.
Qin N, Zheng B, Yao J, Guo L, Zuo J, Wu L, Zhou J, Liu L, Guo J, Ni S. Influence of H7N9 virus infection and associated treatment on human gut microbiota. Science Rep. 2015;5:14771.
Yang L, Poles MA, Fisch GS, Ma Y, Nossa C, Phelan JA, Pei Z. HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS. 2016;30:19–29.
Zilberman-Schapira G, Zmora N, Itav S, Bashiardes S, Elinav H, Elinav E. The gut microbiome in human immunodeficiency virus infection. BMC Medicine. 2016;14:83.
Hoffmann C, Hill DA, Minkah N, Kirn T, Troy A, Artis D, Bushman F. Community-wide response of the gut microbiota to enteropathogenic Citrobacter rodentium infection revealed by deep sequencing. Infectious Immunology. 2009;77:4668–4678.
Zhang L, Dong D, Jiang C, Li Z, Wang X, Peng Y. Insight into alteration of gut microbiota in Clostridium difficile infection and asymptomatic C. difficile colonization. Anaerobe. 2015;34:1–7.
Seekatz AM, Young VB. Clostridium difficile and the microbiota. Journal Clinical Investigation. 2014;124:4182–4189.
Blanchi J, Goret J, Megraud F. Clostridium difficile infection: A model for disruption of the gut microbiota equilibrium. Digestive Disease. 2016;34:217–220.
Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, capsulized, frozen fecal microbiota transplantation for relapsing Clostridium difficile infection. JAMA. 2014;312:1772–1778.
Bashan A, Gibson TE, Friedman J, Carey VJ, Weiss ST, Hohmann EL, Liu YY. Universality of human microbial dynamics. Nature. 2016;534:259–262.
Xu, Zhang X. Effects of cyclophosphamide on immune system and gut microbiota in mice. Microbiology Resource. 2015;171: 97–106.
Yoo DH, Kim IS, Van Le TK, Jung IH, Yoo HH, Kim DH. Gut microbiota-mediated drug interactions between lovastatin and antibiotics. Drug Metabolism Dispos. 2014;42:1508–1513.
Modi SR, Collins JJ, Relman DA. Antibiotics and the gut microbiota. Journal Clinical Investigation. 2014;124:4212–4218.
Cho I, Yamanishi S, Cox L, Methé BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012;488:621–486.
Shaw SY, Blanchard JF, Bernstein CN. Association between the use of antibiotics the first year of life and pediatric inflammatory bowel disease. American Journal Gastroenterology. 2010;105:2687–2692.
Trasande L, Blustein J, Liu M, Corwin E, Cox LM, Blaser MJ. Infant antibiotic exposures and early-life body mass. Interntional Journal Obese (London). 2013;37:16–23.
Whang A, Nagpal R, Yadav H. Biodirectional drug-microbiome interaction of anti-diabetics. EBioMedicine. 2019;39: 591-602.
Chawla A, Repa JJ, Evans RM, Mangelsdorf DJ. Nuclear receptors and lipid physiology: Opening the X-files. Science. 2001;294(5548):1866–1870.
Sonnenburg JL, Backhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016; 535(7610):56–64.
Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell. 2016;165:1332-1345.
Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandees. Enterotypes of the human gut microbiome. Nature. 2011;473:174–180.
Claes N, Fraussen J, Stinissen P, Hupperts R, Somers V. B cells are multifunctional players in multiple sclerosis pathogenesis: Insights from therapeutic interventions. Frontier Immunology. 2015;6:642.
Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nature Review Immunology. 2009;9(5): 313–323.
Suzuki K, Ha SA, Tsuji M, Fagarasan S. Intestinal IgA synthesis: A primitive form of adaptive immunity that regulates microbial communities in the gut. Seminar Immunology. 2007;19(2):127–135.
Helander A, Miller CL, Myers KS, Neutra MR, Nibert ML. Protective immunoglobulin A and G antibodies bind to overlapping intersubunit epitopes in the head domain of type 1 reovirus adhesin sigma1. Journal Virology. 2004;78(19):10695–10705.
Endesfelder D, Engel M, Davis-Richardson AG, Ardissone AN, Achenbach P, Hummel S, Winkler C, Atkinson M, Schatz D, Triplett E. Towards a functional hypothesis relating anti-islet cell autoimmunity to the dietary impact on microbial communities and butyrate production. Microbiome. 2016;4:17.
Harsch IA, Konturck PC. The role of gut microbiota in obesity and type 2 and type 1 diabetes mellitus. New insights into “Old” diseases. Medical Science (Basel). 2018;6(2):32.
Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell. 2007;130:906–917.
Burger-van Paassen N, Vincent A, Puiman PJ, van der Sluis M, Bouma J, Boehm G, van Goudoever JB, van Seuningen I, Renes IB. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection. Biochemistry Journal; 2009.
Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, Casella G, Drew JC, Ilonen J, Knip M. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. 2011;6:e25792.
Bosi E, Molteni L, Radaelli MG, Folini L, Fermo I, Bazzigaluppi E, Piemonti L, Pastore MR, Paroni R. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia. 2006;49:2824–2827.
Clemente Postigo M, Queipo Ortuño MI, Murri M, Boto Ordoñez M, Pérez Martínez P, Andres Lacueva C. Endotoxin increase after fat overload is related to postprandial hypertriglyceridemia in morbidly obese patients. Journal Lipid Resource. 2012;53: 973–978.
Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007a;56:1761–1772.
Amar J, Burcelin R, Ruidavets J, Cani P, Fauvel J, Alessi M. Energy intake is associated with endotoxemiain apparently healthy men. American Journal Clinical Nutrition. 2008;87:1219–1223.
Manco M, Putignani L, Bottazzo GF. Gut microbiota, lipopolysaccharides and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocrine. Revised. 2010;31:817–844.
Poggi M, Bastelica D, Gual P, Iglesias MA, Gremeaux T, Knauf C. C3H/HeJ mice carrying a Toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. Diabetologia. 2007;50:1267–1276.
Chung S, Lapoint K, Martinez K, Kennedy A, Boysen Sandberg M, McIntosh MK. Preadipocytes mediate lipopolysaccharide-induced inflammation and insulin resistance in primary cultures of newly differentiated human adipocytes. Endocrinology. 2006;147:5340–5351.
Karlsson FH, Tremaroli V, Nookaew I, Bergstrom G, Behre CJ, Fagerberg B. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature. 2013;498(7452):99–103.
Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490(7418):55–60.
Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE. 2010;5:e9085.
Conrad D, Weest S. Bacterial products, changes in adipose tissue lead to insulin resistance and decrease insulin release. Physiology. 2014;29:304.
Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NMJ, Magness S. High-fat diet: Bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. 2010;5:e12191.
Gui T, Shimokado A, Sun Y, Akasaka T, Muragaki Y. Erse roles of macrophages in atherosclerosis: From inflammatory biology to biomarker discovery. Mediatation Inflammation. 2012;693083.
Chen WY, Wang M, Zhang J, Barve SS, McClain CJ, Joshi-Barve S. Acrolein disrupts tight junction proteins and causes endoplasmic reticulum stress-mediated epithelial cell death eading to intestinal barrier dysfunction and permeability. American Journal Pathology. 2017;187: 2686–2697.
Mitra S, Drautz-Moses DI, Alhede M, Maw MT, Liu Y, Purbojati RW. In silico analyses of metagenomes from human atherosclerotic plaque samples. Microbiome. 2015;3:38.
Harris K, Kassis A, Major G, Chou CJ. Is the gut microbiota a new factor contributing to obesity and its metabolic disorders? Journal Obese. 2012;2:87-91.
Chacon MR, Lozano-Bartolome J, Portero-Otin M, Rodriguez MM, Xifra G, Puig J. The gut mycobiome composition is linked to carotid atherosclerosis. Benefical Microbes. 2017;9:14.
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.
Neves AL, Coelho J, Couto L, Leite-Moreira A. Metabolic endotoxemia: A molecular link between obesity and cardiovascular risk. Journal Molecular Endocrinology. 2013;51:R51–R64.
Turnbaugh PJ, Gordon JI. The core gut microbiome, energy balance and obesity. Journal Physiology. 2009;587(17):4153–4158.
Robertson MD, Wright JW, Loizon E, Debard C, Vidal H, Shojaee-Moradie F. Insulin-sensitizing effects on muscle and adipose tissue after dietary fiber intake in men and women with metabolic syndrome. Journal Clinical Endocrinology Metabolism. 2012;97(9):3326–332.
Scheithauer TP, Dallinga-Thie GM, de Vos WM, Nieuwdorp M, van Raalte H. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Molecular Metabolism. 2016;5(9):759–770.
Link A, Becker V, Goel A, Wex T, Malfertheiner P. Feasibility of fecal microRNAs as novel biomarkers for pancreatic cancer. PLoS One. 2012;8: e42933.
Zhernakova A, Kurilshikov A, Bonder MJ, Tigchelaar EF, Schirmer M, Vatanen T. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 2016;352(6285):565–569.
Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Dsiabetes. 2009;58(7):1509–1517.
Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190–195.
Griffin NW, Ahern PP, Cheng J, Heath AC, Ilkayeva O, Newgard CB. Prior dietary practices and connections to a human gut microbial metacommunity alter responses to diet interventions. Cell Host Microbe. 2017;21(1):84–96.
Tang WHW, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. Journal of Clinical Investigation. 2014;124(10):4204-4211.
Evenepoel P, Meijers BK, Bammens BR, Verbeke K. Uremic toxins originating from colonic microbial metabolism. Kidney International. 2009;114:S12–19.
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. Procedure Natural Academic Science USA. 2009;106:3698– 3707.
Fukagawa M, Watanabe Y. Role of uremic toxins and oxidative stress in chronic kidney disease. Therapy Apher Dial. 2011;15:119.
Poesen R, Meijers B, Evenepoel P. The colon: An overlooked site for therapeutics in dialysis patients. Semin Dial. 2013;26: 323–332.
Meijers BK, Claes K, Bammens B, de Loor H, Viaene L, Verbeke K, Kuypers D, Vanrenterghem Y, Evenepoel P. p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clinical Journal American Society Nephrology. 2010;5:1182–1189.
Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y. Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney International. 2006;69:1081–1087.
Missailidis C, Hallqvist J, Qureshi AR, Barany P, Heimburger O, Lindholm B, Stenvinkel P, Bergman P. Serum Trimethylamine-N-oxide is strongly related to renal function and predicts outcome in chronic kidney disease. 2016;11:141738.
Kalantar-Zadeh K, Kopple JD, Deepak S, Block D, Block G. Food intake characteristics of hemodialysis patients as obtained by food frequency questionnaire. Journal Renal Nutrition. 2002;12:17– 31.
Jakobsson HE, Jernberg C, Andersson AF, Sjolund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. 2010;5:9836.
Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 2015;88:958–966.