Ogurtsova K, da Rocha Fernandes JD, Huaeng Y et al (2017) IDF DIABETES Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 128:40–50. https:// doi.org/10.1016/j.diabres.2017.03.024
Saeedi P, Petersohn I, Salpea P et al (2019) Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation diabetes atlas, 9th edition. Diabetes Res Clin Pract 157:107843. https://doi.org/10.1016/j.diabres.2019.107843
Snijder MB, Agyemang C, Peters RJ, Stronks K, Ujcic-Voortman JK, van Valkengoed IG (2017) Case finding and medical treatment of type 2 diabetes among different ethnic minority groups: the HELIUS study. J Diabetes Res 2017:9896849. https://doi.org/ 10.1155/2017/9896849
Cheng YJ, Kanaya AM, Araneta MRG et al (2019) Prevalence of diabetes by race and ethnicity in the United States, 2011-2016. JAMA 322(24):2389–2398. https://doi.org/10.1001/jama.2019. 19365
Tillin T, Hughes AD, Godsland IF et al (2013) Insulin resistance and truncal obesity as important determinants of the greater incidence of diabetes in Indian Asians and African Caribbeans compared with Europeans: the Southall And Brent REvisited (SABRE) cohort. Diabetes Care 36(2):383–393. https://doi.org/ 10.2337/dc12-0544
Mahajan A, Wessel J, Willems SM et al (2018) Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat Genet 50(4):559–571. https://doi.org/10.1038/s41588-018-0084-1
McCarthy MI (2010) Genomics, type 2 diabetes, and obesity. N Engl J Med 363(24):2339–2350. https://doi.org/10.1056/ NEJMra0906948
Morris AP, Voight BF, Teslovich TM et al (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44(9):981– 990. https://doi.org/10.1038/ng.2383
Saklayen MG (2018) The global epidemic of the metabolic syndrome. Curr Hypertens Rep 20(2):12. https://doi.org/10. 1007/s11906-018-0812-z
Cotillard A, Kennedy SP, Kong LC et al (2013) Dietary intervention impact on gut microbial gene richness. Nature 500(7464): 585–588. https://doi.org/10.1038/nature12480
Le Chatelier E, Nielsen T, Qin J et al (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500(7464):541–546. https://doi.org/10.1038/nature12506
Li SS, Zhu A, Benes V et al (2016) Durable coexistence of donor and recipient strains after fecal microbiota transplantation. Science 352(6285):586–589. https://doi.org/10.1126/science.aad8852
Del Chierico F, Abbatini F, Russo A et al (2018) Gut microbiota markers in obese adolescent and adult patients: age-dependent differential patterns. Front Microbiol 9:1210. https://doi.org/10. 3389/fmicb.2018.01210
Ussar S, Griffin NW, Bezy O et al (2015) Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome. Cell Metab 22(3):516–530. https://doi.org/10.1016/j.cmet.2015.07.007
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027– 1031. https://doi.org/10.1038/nature05414
. Ridaura VK, Faith JJ, Rey FE et al (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150):1241214. https://doi.org/10.1126/science. 1241214
Kootte RS, Levin E, Salojarvi J et al (2017) Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab 26(4):611–619 e616. https://doi.org/10.1016/j.cmet.2017. 09.008
Vrieze A, Van Nood E, Holleman F et al (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143(4): 913–916. https://doi.org/10.1053/j.gastro.2012.06.031
de Groot P, Scheithauer T, Bakker GJ et al (2020) Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut 69(3):502–512. https://doi.org/10.1136/ gutjnl-2019-318320
Gurung M, Li Z, You H et al (2020) Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine 51:102590. https:// doi.org/10.1016/j.ebiom.2019.11.051
Wu G, Zhang C, Wu H et al (2017) Genomic microdiversity of Bifidobacterium pseudocatenulatum underlying differential strain-level responses to dietary carbohydrate intervention. mBio 8(1):e02348–16. https://doi.org/10.1128/mBio.02348-16
Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023. https://doi.org/10.1038/4441022a
Murphy EF, Cotter PD, Healy S et al (2010) Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut 59(12):1635–1642. https://doi.org/10.1136/gut.2010.215665
Duncan SH, Lobley GE, Holtrop G et al (2008) Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes 32(11):1720–1724. https://doi.org/10.1038/ijo.2008.155
Zhang H, DiBaise JK, Zuccolo A et al (2009) Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 106(7):2365–2370. https://doi.org/10.1073/pnas.0812600106
Schwiertz A, Taras D, Schafer K et al (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18(1): 190–195. https://doi.org/10.1038/oby.2009.167
Karlsson FH, Tremaroli V, Nookaew I et al (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498(7452):99–103. https://doi. org/10.1038/nature12198
Larsen N, Vogensen FK, van den Berg FW et al (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5(2):e9085. https://doi.org/10. 1371/journal.pone.0009085
Qin J, Li Y, Cai Z et al (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490(7418):55– 60. https://doi.org/10.1038/nature11450
Cani PD, Amar J, Iglesias MA et al (2007) Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 56(7):1761–1772. https://doi.org/10.2337/db06-1491
Lassenius MI, Pietilainen KH, Kaartinen K et al (2011) Bacterial endotoxin activity in human serum is associated with dyslipidemia, insulin resistance, obesity, and chronic inflammation. Diabetes Care 34(8):1809–1815. https://doi.org/10.2337/dc10- 2197
Serpa J, Caiado F, Carvalho T et al (2010) Butyrate-rich colonic microenvironment is a relevant selection factor for metabolically adapted tumor cells. J Biol Chem 285(50):39211–39223. https:// doi.org/10.1074/jbc.M110.156026
Flint HJ, Duncan SH, Scott KP, Louis P (2015) Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc 74(1):13–22. https://doi.org/10.1017/S0029665114001463
de la Cuesta-Zuluaga J, Mueller NT, Alvarez-Quintero R et al (2018) Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors. Nutrients 11(1). https://doi.org/10. 3390/nu11010051
Rahat-Rozenbloom S, Fernandes J, Gloor GB, Wolever TM (2014) Evidence for greater production of colonic short-chain fatty acids in overweight than lean humans. Int J Obes 38(12): 1525–1531. https://doi.org/10.1038/ijo.2014.46
Jumpertz R, Le DS, Turnbaugh PJ et al (2011) Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr 94(1):58–65. https://doi.org/10.3945/ajcn.110.010132
Dominguez-Bello MG, De Jesus-Laboy KM, Shen N et al (2016) Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 22(3):250–253. https://doi. org/10.1038/nm.4039
Backhed F, Roswall J, Peng Y et al (2015) Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17(5):690–703. https://doi.org/10.1016/j. chom.2015.04.004
Steinert A, Radulovic K, Niess J (2016) Gastro-intestinal tract: the leading role of mucosal immunity. Swiss Med Wkly 146:w14293. https://doi.org/10.4414/smw.2016.14293
Miki T, Goto R, Fujimoto M, Okada N, Hardt WD (2017) The bactericidal lectin RegIIIβ prolongs gut colonization and enteropathy in the streptomycin mouse model for Salmonella diarrhea. Cell Host Microbe 21(2):195–207. https://doi.org/10.1016/j. chom.2016.12.008
Devlin AS, Fischbach MA (2015) A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat Chem Biol 11(9):685–690. https://doi.org/10.1038/nchembio.1864
Niess JH, Leithauser F, Adler G, Reimann J (2008) Commensal gut flora drives the expansion of proinflammatory CD4 T cells in the colonic lamina propria under normal and inflammatory conditions. J Immunol 180(1):559–568. https://doi.org/10.4049/ jimmunol.180.1.559
Ivanov II, Atarashi K, Manel N et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139(3):485– 498. https://doi.org/10.1016/j.cell.2009.09.033
Yang H, Yu HB, Bhinder G et al (2019) TLR9 limits enteric antimicrobial responses and promotes microbiota-based colonisation resistance during Citrobacter rodentium infection. Cell Microbiol 21(7):e13026. https://doi.org/10.1111/cmi.13026
Cohen LJ, Kang HS, Chu J et al (2015) Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist. Proc Natl Acad Sci U S A 112(35):E4825–E4834. https://doi.org/10. 1073/pnas.1508737112
Caruso R, Lo BC, Nunez G (2020) Host-microbiota interactions in inflammatory bowel disease. Nat Rev Immunol 20(7):411–426. https://doi.org/10.1038/s41577-019-0268-7
Kinugasa T, Sakaguchi T, Gu X, Reinecker HC (2000) Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 118(6):1001–1011. https://doi.org/10.1016/ s0016-5085(00)70351-9
Salzman NH, Hung K, Haribhai D et al (2010) Enteric defensins are essential regulators of intestinal microbial ecology. Nat Immunol 11(1):76–83. https://doi.org/10.1038/ni.1825
Smythies LE, Sellers M, Clements RH et al (2005) Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest 115(1): 66–75. https://doi.org/10.1172/JCI19229
Moor K, Diard M, Sellin ME et al (2017) High-avidity IgA protects the intestine by enchaining growing bacteria. Nature 544(7651):498–502. https://doi.org/10.1038/nature22058
Donaldson GP, Ladinsky MS, Yu KB et al (2018) Gut microbiota utilize immunoglobulin A for mucosal colonization. Science 360(6390):795–800. https://doi.org/10.1126/science.aaq0926
Balmer ML, Slack E, de Gottardi A et al (2014) The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med 6(237):237ra266. https:// doi.org/10.1126/scitranslmed.3008618
Massier L, Chakaroun R, Tabei S et al (2020) Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes. Gut. https://doi.org/10.1136/gutjnl-2019-320118
Sookoian S, Salatino A, Castano GO et al (2020) Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease. Gut 69:1483–1491. https://doi.org/10.1136/gutjnl-2019- 318811
Tilg H, Zmora N, Adolph TE, Elinav E (2020) The intestinal microbiota fuelling metabolic inflammation. Nat Rev Immunol 20(1):40–54. https://doi.org/10.1038/s41577-019-0198-4
Wikoff WR, Anfora AT, Liu J et al (2009) Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A 106(10):3698–3703. https://doi. org/10.1073/pnas.0812874106
Guasch-Ferre M, Hruby A, Toledo E et al (2016) Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis. Diabetes Care 39(5):833–846. https://doi.org/10.2337/dc15-2251
Rabaglia ME, Gray-Keller MP, Frey BL, Shortreed MR, Smith LM, Attie AD (2005) α-Ketoisocaproate-induced hypersecretion of insulin by islets from diabetes-susceptible mice. Am J Physiol Endocrinol Metab 289(2):E218–E224. https://doi.org/10.1152/ ajpendo.00573.2004
Yang J, Chi Y, Burkhardt BR, Guan Y, Wolf BA (2010) Leucine metabolism in regulation of insulin secretion from pancreatic beta cells. Nutr Rev 68(5):270–279. https://doi.org/10.1111/j.1753- 4887.2010.00282.x
Myhrvold C, Kotula JW, Hicks WM, Conway NJ, Silver PA (2015) A distributed cell division counter reveals growth dynamics in the gut microbiota. Nat Commun 6:10039. https://doi.org/ 10.1038/ncomms10039
Li H, Limenitakis JP, Fuhrer T et al (2015) The outer mucus layer hosts a distinct intestinal microbial niche. Nat Commun 6:8292. https://doi.org/10.1038/ncomms9292
El Aidy S, Merrifield CA, Derrien M et al (2013) The gut microbiota elicits a profound metabolic reorientation in the mouse jejunal mucosa during conventionalisation. Gut 62(9):1306–1314. https://doi.org/10.1136/gutjnl-2011-301955
Nicholls AW, Mortishire-Smith RJ, Nicholson JK (2003) NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats. Chem Res Toxicol 16(11):1395–1404. https://doi.org/10.1021/tx0340293
Williams RE, Eyton-Jones HW, Farnworth MJ, Gallagher R, Provan WM (2002) Effect of intestinal microflora on the urinary metabolic profile of rats: a 1 H-nuclear magnetic resonance spectroscopy study. Xenobiotica 32(9):783–794. https://doi.org/10. 1080/00498250210143047
Uchimura Y, Fuhrer T, Li H et al (2018) Antibodies set boundaries limiting microbial metabolite penetration and the resultant mammalian host response. Immunity 49(3):545–559. https://doi. org/10.1016/j.immuni.2018.08.004
Yang C, Mogno I, Contijoch EJ et al (2020) Fecal IgA levels are determined by strain-level differences in bacteroides ovatus and are modifiable by gut microbiota manipulation. Cell Host Microbe 27(3):467–475. https://doi.org/10.1016/j.chom.2020.01.016
Hapfelmeier S, Lawson MA, Slack E et al (2010) Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328(5986):1705–1709. https://doi.org/10.1126/science.11884