Skip to main content
Top
Published in: Current Obesity Reports 3/2019

01-09-2019 | Obesity | Metabolism (M Dalamaga, Section Editor)

Understanding the Role of the Gut Microbiome and Microbial Metabolites in Obesity and Obesity-Associated Metabolic Disorders: Current Evidence and Perspectives

Authors: Natalia Vallianou, Theodora Stratigou, Gerasimos Socrates Christodoulatos, Maria Dalamaga

Published in: Current Obesity Reports | Issue 3/2019

Login to get access

Abstract

Purpose

In this review, we summarize current evidence on the gut microbiome and microbial metabolites in relation to obesity and obesity-associated metabolic disorders. Special emphasis is given on mechanisms interconnecting gut microbiome and microbial metabolites with metabolic disorders as well as on potential preventive and therapeutic perspectives with a “bench to bedside” approach.

Recent Findings

Recent data have highlighted the role of gut dysbiosis in the etiology and pathogenesis of metabolic disorders, including obesity, metabolic syndrome, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Overall, most studies have demonstrated a reduction in gut microbiome diversity and richness in obese subjects, but there is still much debate on the exact microbial signature of a healthy or an obese gut microbiome. Despite the controversial role of an altered gut microbiome as a cause or consequence of obesity in human studies, numerous animal studies and certain human studies suggest beneficial metabolic effects of certain microbial intestinal metabolites, such as butyrate, that could be used in the prevention and treatment of obesity and its comorbidities.

Summary

More randomized controlled trials and larger prospective studies including well-defined cohorts as well as a multi-omics approach are warranted to better identify the associations between the gut microbiome, microbial metabolites, and obesity and its metabolic complications.
Literature
22.
go back to reference • Vallianou NG, Stratigou T, Tsagarakis S. Microbiome and diabetes: where are we now? Diabetes Res Clin Pract. 2018;146:111–8. https://doi.org/10.1016/j.diabres.2018.10.008 This review highlights the role of prebiotics, probiotics, genetically modified bacteria, and fecal microbiota transplantation, as potential therapeutic perspectives and challenges for type 2 diabetes.CrossRefPubMed • Vallianou NG, Stratigou T, Tsagarakis S. Microbiome and diabetes: where are we now? Diabetes Res Clin Pract. 2018;146:111–8. https://​doi.​org/​10.​1016/​j.​diabres.​2018.​10.​008 This review highlights the role of prebiotics, probiotics, genetically modified bacteria, and fecal microbiota transplantation, as potential therapeutic perspectives and challenges for type 2 diabetes.CrossRefPubMed
32.
go back to reference •• Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214. https://doi.org/10.1126/science.1241214 This study shows that gut microbiota from twins discordant for obesity may modulate metabolism in mice revealing that obesity-associated metabolic phenotypes were transmissible with fecal transplantation.CrossRefPubMed •• Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214. https://​doi.​org/​10.​1126/​science.​1241214 This study shows that gut microbiota from twins discordant for obesity may modulate metabolism in mice revealing that obesity-associated metabolic phenotypes were transmissible with fecal transplantation.CrossRefPubMed
42.
44.
50.
go back to reference •• Tremaroli V, Karlsson F, Werling M, Stahlman M, Kovatcheva-Datchary P, Olbers T, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228–38. https://doi.org/10.1016/j.cmet.2015.07.009 The results of this study show that after bariatric surgery, the gut microbiota may play a direct role in the reduction of adiposity.CrossRefPubMedPubMedCentral •• Tremaroli V, Karlsson F, Werling M, Stahlman M, Kovatcheva-Datchary P, Olbers T, et al. Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 2015;22:228–38. https://​doi.​org/​10.​1016/​j.​cmet.​2015.​07.​009 The results of this study show that after bariatric surgery, the gut microbiota may play a direct role in the reduction of adiposity.CrossRefPubMedPubMedCentral
53.
go back to reference Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13:514–22. https://doi.org/10.1038/tpj.2012.43.CrossRefPubMed Graessler J, Qin Y, Zhong H, Zhang J, Licinio J, Wong ML, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13:514–22. https://​doi.​org/​10.​1038/​tpj.​2012.​43.CrossRefPubMed
57.
go back to reference •• Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019. https://doi.org/10.1038/s41574-019-0156-z This review focuses on the role of metabolites derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD. •• Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. 2019. https://​doi.​org/​10.​1038/​s41574-019-0156-z This review focuses on the role of metabolites derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD.
58.
go back to reference den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARgamma-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64:2398–408. https://doi.org/10.2337/db14-1213.CrossRef den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARgamma-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64:2398–408. https://​doi.​org/​10.​2337/​db14-1213.CrossRef
65.
go back to reference •• Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vich Vila A, Vosa U, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019. https://doi.org/10.1038/s41588-019-0350-x . This study provides evidence of a causal effect of the gut microbiome and its metabolites on metabolic traits. •• Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vich Vila A, Vosa U, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019. https://​doi.​org/​10.​1038/​s41588-019-0350-x . This study provides evidence of a causal effect of the gut microbiome and its metabolites on metabolic traits.
68.
go back to reference •• Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535:376–81. https://doi.org/10.1038/nature18646 This study suggests that microbial metabolites may have the potential to diminish insulin resistance and to decrease the incidence of common metabolic and cardiovascular disorders.CrossRefPubMed •• Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature. 2016;535:376–81. https://​doi.​org/​10.​1038/​nature18646 This study suggests that microbial metabolites may have the potential to diminish insulin resistance and to decrease the incidence of common metabolic and cardiovascular disorders.CrossRefPubMed
96.
go back to reference Rexrode KM, Pradhan A, Manson JE, Buring JE, Ridker PM. Relationship of total and abdominal adiposity with CRP and IL-6 in women. Ann Epidemiol. 2003;13:674–82.CrossRefPubMed Rexrode KM, Pradhan A, Manson JE, Buring JE, Ridker PM. Relationship of total and abdominal adiposity with CRP and IL-6 in women. Ann Epidemiol. 2003;13:674–82.CrossRefPubMed
100.
go back to reference Munkholm P, Langholz E, Hollander D, Thornberg K, Orholm M, Katz KD, et al. Intestinal permeability in patients with Crohn’s disease and ulcerative colitis and their first degree relatives. Gut. 1994;35:68–72.CrossRefPubMedPubMedCentral Munkholm P, Langholz E, Hollander D, Thornberg K, Orholm M, Katz KD, et al. Intestinal permeability in patients with Crohn’s disease and ulcerative colitis and their first degree relatives. Gut. 1994;35:68–72.CrossRefPubMedPubMedCentral
103.
go back to reference Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med. 1994;179:269–77.CrossRefPubMed Hailman E, Lichenstein HS, Wurfel MM, Miller DS, Johnson DA, Kelley M, et al. Lipopolysaccharide (LPS)-binding protein accelerates the binding of LPS to CD14. J Exp Med. 1994;179:269–77.CrossRefPubMed
104.
go back to reference Le Roy D, Di Padova F, Tees R, Lengacher S, Landmann R, Glauser MP, et al. Monoclonal antibodies to murine lipopolysaccharide (LPS)-binding protein (LBP) protect mice from lethal endotoxemia by blocking either the binding of LPS to LBP or the presentation of LPS/LBP complexes to CD14. J Immunol. 1999;162:7454–60.PubMed Le Roy D, Di Padova F, Tees R, Lengacher S, Landmann R, Glauser MP, et al. Monoclonal antibodies to murine lipopolysaccharide (LPS)-binding protein (LBP) protect mice from lethal endotoxemia by blocking either the binding of LPS to LBP or the presentation of LPS/LBP complexes to CD14. J Immunol. 1999;162:7454–60.PubMed
110.
113.
116.
go back to reference Anhe FF, Roy D, Pilon G, Dudonne S, Matamoros S, Varin TV, et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64:872–83. https://doi.org/10.1136/gutjnl-2014-307142.CrossRefPubMed Anhe FF, Roy D, Pilon G, Dudonne S, Matamoros S, Varin TV, et al. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015;64:872–83. https://​doi.​org/​10.​1136/​gutjnl-2014-307142.CrossRefPubMed
119.
go back to reference Bahmani F, Tajadadi-Ebrahimi M, Kolahdooz F, Mazouchi M, Hadaegh H, Jamal AS, et al. The consumption of synbiotic bread containing Lactobacillus sporogenes and inulin affects nitric oxide and malondialdehyde in patients with type 2 diabetes mellitus: randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. 2016;35:506–13. https://doi.org/10.1080/07315724.2015.1032443.CrossRefPubMed Bahmani F, Tajadadi-Ebrahimi M, Kolahdooz F, Mazouchi M, Hadaegh H, Jamal AS, et al. The consumption of synbiotic bread containing Lactobacillus sporogenes and inulin affects nitric oxide and malondialdehyde in patients with type 2 diabetes mellitus: randomized, double-blind, placebo-controlled trial. J Am Coll Nutr. 2016;35:506–13. https://​doi.​org/​10.​1080/​07315724.​2015.​1032443.CrossRefPubMed
129.
go back to reference • Vallianou N, Liu J, Dalamaga M. What are the key points in the association between the gut microbiome and nonalcoholic fatty liver disease? Metabolism Open 2019;1:9–10. https://doi.org/10.1016/j.metop.2019.02.003. In press. This mini-review underscores the key points in the association between the gut microbiome and NAFLD. • Vallianou N, Liu J, Dalamaga M. What are the key points in the association between the gut microbiome and nonalcoholic fatty liver disease? Metabolism Open 2019;1:9–10. https://​doi.​org/​10.​1016/​j.​metop.​2019.​02.​003. In press. This mini-review underscores the key points in the association between the gut microbiome and NAFLD.
133.
go back to reference Ruiz AG, Casafont F, Crespo J, Cayon A, Mayorga M, Estebanez A, et al. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes Surg. 2007;17:1374–80. https://doi.org/10.1007/s11695-007-9243-7.CrossRefPubMed Ruiz AG, Casafont F, Crespo J, Cayon A, Mayorga M, Estebanez A, et al. Lipopolysaccharide-binding protein plasma levels and liver TNF-alpha gene expression in obese patients: evidence for the potential role of endotoxin in the pathogenesis of non-alcoholic steatohepatitis. Obes Surg. 2007;17:1374–80. https://​doi.​org/​10.​1007/​s11695-007-9243-7.CrossRefPubMed
Metadata
Title
Understanding the Role of the Gut Microbiome and Microbial Metabolites in Obesity and Obesity-Associated Metabolic Disorders: Current Evidence and Perspectives
Authors
Natalia Vallianou
Theodora Stratigou
Gerasimos Socrates Christodoulatos
Maria Dalamaga
Publication date
01-09-2019
Publisher
Springer US
Published in
Current Obesity Reports / Issue 3/2019
Electronic ISSN: 2162-4968
DOI
https://doi.org/10.1007/s13679-019-00352-2

Other articles of this Issue 3/2019

Current Obesity Reports 3/2019 Go to the issue

Obesity Treatment (CM Apovian, Section Editor)

Nonalcoholic Fatty Liver Disease and Obesity Treatment