Our second genome and the impact on metabolic disorders: why gut microbiome is an important player in diabetes and associated abnormalities

Acta Diabetologica, Mar 2019

Massimo Federici

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Our second genome and the impact on metabolic disorders: why gut microbiome is an important player in diabetes and associated abnormalities

Acta Diabetologica pp 1–2 | Cite as Our second genome and the impact on metabolic disorders: why gut microbiome is an important player in diabetes and associated abnormalities AuthorsAuthors and affiliations Massimo Federici Editorial First Online: 25 March 2019 5 Shares 204 Downloads Part of the following topical collections:Gut Microbiome and Metabolic Disorders Managed by Massimo Federici. Disorders of the gut microbiome have been connected to a multitude of adverse conditions, including obesity, type 2 diabetes, cardiovascular diseases, inflammatory bowel diseases, anxiety, autism, allergies, and autoimmune diseases. Despite the overall skepticism, in the past decade, growing evidence has shown that the composition of the gut microbiota and its activity might be associated with perturbation of the nutrients’ absorption and the onset of inflammation in the host [1]. Therefore, the gut microbiome might “coordinate” individual responses to environmental factors to explain penetrance of certain disorders beyond genetics [2]. It has been also recently hypothesized that loss of the microbiota–host equilibrium may explain the onset of “pre-disease” states (pre-diabetes, pre-hypertension, etc.) and thus explain the explosive development of chronic diseases such as inflammatory bowel disease, obesity, and other metabolic/inflammatory disorders [3]. Recent data suggest that alterations in gut microbial and metabolic composition may be responsible, in part, for induction of chronic inflammation, thus promoting glucose intolerance and cardiovascular disease [4, 5]. In obesity, diabetes and Non Alcoholic Fatty Liver Disease bacterial diversity differs between lean and obese, with increase in Firmicutes to the detriment of Bacteroidetes as well as an overabundance or depletion of certain species, including Prevotella copri and Akkermansia muciniphila [5, 6, 7]. Most of the studies employing metagenomics methods found that metabolic disorders are associated to reduced measures of bacterial gene count or richness [8, 9]. Patients with insulin resistance and steatosis show signs of reduced microbial gene richness and increased genetic potential for processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid (AAA and BCAA) metabolism [10]. In subjects with NAFLD disease progression to advanced fibrosis is characterized by statistically significant increase in abundance of the Proteobacteria phylum a while the Firmicutes phylum decreases [11]. Analysis of microbiota communities in human oral, gut, and atherosclerotic plaques from individuals with established atherosclerosis showed a reproducible correlation between CVD and bacterial pathogens, including Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori, and Aggregatibacter actinomycetemcomitans [12]. Another study found that Collinsella spp. are enriched in subjects with atherosclerosis, while Eubacterium spp. and Roseburia spp. are more abundant among healthy controls [13]. Finally, research over the past decade has uncovered several key microbial metabolites, such as trimethylamine-N-oxide (TMAO), short-chain fatty acids (SCFAs) and secondary bile acids that uniquely affect the progression of CVD [5]. Few contributions about microbiota were published in Acta Diabetologica in the last 5 years [14, 15, 16, 17, 18]. However, given its relevance, we open a new topical collection dedicated to the gut microbiome and its impact on metabolic disorders. Dumas and colleagues discussed the relevance of Diet-Induced Metabolic Changes of the Human Gut Microbiome and in particular they focus on microbie-derived metabolites such as short-chain fatty acids, methylamines and indoles [19]. Fernandez Real and colleagues showed new evidence connecting glutamate to gut microbiota composition and metabolic phenotypes [20]. Finally, Liang Ma and colleagues illustrated the links between gut microbiota and diabetic nephropathy [21]. We call for new submissions to Acta Diabetologica to enrich the gut microbiome open-ended topical collection. Notes Funding M.F. work related to this manuscript was in part funded by EU-FP7 FLORINASH (Health- F2-2009-241913), Ministry of University (MIUR) Progetti di Ricerca di Interesse Nazionale (PRIN) protocol number 2015MPESJS_004 and 2017FM74HK. Compliance with ethical standards Conflict of interest The author is co-inventor on pending patents held by INSERM Transfert, INSERM, University of Rome Tor Vergata, University of Girona and Imperial College on NAFLD diagnostics and has the right to receive royalty payments for inventions or discoveries related to NAFLD diagnostics. Ethical approval This article is a commentary and does not contain directly studies with human participants or animals performed by the author. Informed consent For this type of study formal consent is not required . Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R (2018) Current understanding of the human microbiome. Nat Med 24(4):392–400CrossRefGoogle Scholar 2. Clemente JC, Manasson J, Scher JU (2018) The role of the gut microbiome in systemic inflammatory disease. BMJ 360:j5145CrossRefGoogle Scholar 3. van de Guchte M, Blottière HM, Doré J (2018) Humans as holobionts: implications for prevention and therapy. Microbiome 6(1):81CrossRefGoogle Scholar 4. Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, Le Chatelier E, Levenez F, Doré J, Mattila I, Plichta DR, Pöhö P, Hellgren LI, Arumugam M, Sunagawa S, Vieira-Silva S, Jørgensen T, Holm JB, Trošt K, MetaHIT C, Kristiansen K, Brix S, Raes J, Wang J, Hansen T, Bork P, Brunak S, Oresic M, Ehrlich SD, Pedersen O (2016) Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535(7612):376–381CrossRefGoogle Scholar 5. Brown JM, Hazen SL (2018 Mar) Microbial modulation of cardiovascular disease. Nat Rev Microbiol 16(3):171–181CrossRefGoogle Scholar 6. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023CrossRefGoogle Scholar 7. Dao MC, Everard A, Aron-Wisnewsky J, Sokolovska N, Prifti E, Verger EO, Kayser BD, Levenez F, Chilloux J, Hoyles L, MICRO-Obes Consortium, Dumas ME, Rizkalla SW, Doré J, Cani PD, Clément K (2016) Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut 65(3):426–436CrossRefGoogle Scholar 8. Karlsson FH, Tremaroli V, Nookaew I, Bergström G, Behre CJ, Fagerberg B, Nielsen J, Bäckhed F (2013) Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 498(7452):99–103CrossRefGoogle Scholar 9. Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, Leonard P, Li J, Burgdorf K, Grarup N, Jørgensen T, Brandslund I, Nielsen HB, Juncker AS, Bertalan M, Levenez F, Pons N, Rasmussen S, Sunagawa S, Tap J, Tims S, Zoetendal EG, Brunak S, Clément K, Doré J, Kleerebezem M, Kristiansen K, Renault P, Sicheritz-Ponten T, de Vos WM, Zucker JD, Raes J, Hansen T, MetaHIT consortium, Bork P Wang J, Ehrlich SD, Pedersen O (2013) Richness of human gut microbiome correlates with metabolic markers. Nature 500(7464):541–546CrossRefGoogle Scholar 10. Hoyles L, Fernández-Real JM, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Latorre Luque J, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez- Gili L, Moreno-Navarrete JM, Benhamed F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentileschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas ME (2018) Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nat Med 24(7):1070–1080CrossRefGoogle Scholar 11. Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A, Dulai PS, Caussy C, Bettencourt R, Highlander SK, Jones MB, Sirlin CB, Schnabl B, Brinkac L, Schork N, Chen CH, Brenner DA, Biggs W, Yooseph S, Venter JC, Nelson KE (2017) Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab 25(5):1054–1062CrossRefGoogle Scholar 12. Lindskog Jonsson A, Hållenius FF, Akrami R, Johansson E, Wester P, Arnerlöv C, Bäckhed F, Bergström G (2017) Bacterial profile in human atherosclerotic plaques. Atherosclerosis 263:177–183CrossRefGoogle Scholar 13. Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J (2012) Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun 3:1245CrossRefGoogle Scholar 14. Mokkala K, Houttu N, Vahlberg T, Munukka E, Rönnemaa T, Laitinen K (2017) Gut microbiota aberrations precede diagnosis of gestational diabetes mellitus. Acta Diabetol 54(12):1147–1149.  https://doi.org/10.1007/s00592-017-1056-0 CrossRefGoogle Scholar 15. Kallio KA, Hätönen KA, Lehto M, Salomaa V, Männistö S, Pussinen PJ (2015) Endotoxemia, nutrition, and cardiometabolic disorders. Acta Diabetol 52(2):395–404CrossRefGoogle Scholar 16. Serino M, Fernández-Real JM, García-Fuentes E, Queipo-Ortuño M, Moreno-Navarrete JM, Sánchez A, Burcelin R, Tinahones F (2013) The gut microbiota profile is associated with insulin action in humans. Acta Diabetol 50(5):753–761CrossRefGoogle Scholar 17. Burcelin R, Serino M, Chabo C, Blasco-Baque V, Amar J (2011) Gut microbiota and diabetes: from pathogenesis to therapeutic perspective. Acta Diabetol 48(4):257–273CrossRefGoogle Scholar 18. Barrett HL, Callaway LK, Nitert MD (2012) Probiotics: a potential role in the prevention of gestational diabetes? Acta Diabetol 49(Suppl 1):S1–S13CrossRefGoogle Scholar 19. Rahim MBadrinHAbdul, Chilloux J, Martinez-Gili L, Neves AL, Myridakis A, Gooderham N, Dumas M-E (2019) Diet-induced metabolic changes of the human gut microbiome: importance of short-chain fatty acids, methylamines and indoles. Acta Diabetol.  https://doi.org/10.1007/s00592-019-01312-x Google Scholar 20. Palomo-Buitrago ME, Sabater-Masdeu M, Moreno-Navarrete JM, Caballano-Infantes E, Arnoriaga-Rodríguez M, Coll C, Ramió L, Palomino-Schätzlein M, Gutiérrez-Carcedo P, Pérez-Brocal V, Simó R, Moyae A, Ricart W, Herance JR, Fernández-Real JM (2019) Glutamate interactions with obesity, insulin resistance, cognition and gut microbiota composition. Acta Diabetol.  https://doi.org/10.1007/s00592-019-01313-w Google Scholar 21. Tao S, Li L, Ling L, Liu Y, Ren Q, Shi M, Liu J, Jiang J, Ma H, Huang Z, Xia Z, Pan J, Wei T, Wang Y, Li P, Lan T, Tang X, Zeng X, Lei S, Tang H, Ma L, Fu P (2019) Understanding the gut-kidney axis among biopsy-proven diabetic nephropathy, type 2 diabetes mellitus and healthy controls: an analysis of the gut microbiota composition. Acta Diabetol.  https://doi.org/10.1007/s00592-019-01316-7 Google Scholar Copyright information © Springer-Verlag Italia S.r.l., part of Springer Nature 2019 Authors and Affiliations Massimo Federici1Email author1.Department of Systems MedicineUniversity of Rome Tor VergataRomeItaly

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Massimo Federici. Our second genome and the impact on metabolic disorders: why gut microbiome is an important player in diabetes and associated abnormalities, Acta Diabetologica, 2019, 1-2, DOI: 10.1007/s00592-019-01315-8