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Diabetes, Obesity and the Gut Microbiome
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Diabetes, Obesity and the Gut Microbiome

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Microbial Genetics and Genomics".

Deadline for manuscript submissions: closed (31 October 2017) | Viewed by 73608

Special Issue Editors

Dr. Gerard E. Mullin

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Guest Editor
Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, USA
Interests: nutrition; inflammatory bowel disease; digital health; technology; epidemiology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Laura Matarese

E-Mail Website
Guest Editor
Department of Internal Medicine, Brody School of Medicine East Carolina University, 600 Moye Blvd. Vidant MA 342, Mail Stop 734, Greenville, NC 27834, USA
Interests: clinical nutrition; gastroenterology; inflammatory bowel disease; nutrition assessment

Special Issue Information

Dear Colleagues,

The gut microbiome is an interactive network of trillions of microbes that synergize to provide epigenetic regulation of the host and impacting a number of crucial physiological functions. Establishment of the gut microbiome is influenced by the mode of birth, breastfeeding, provision of prebiotic foods, antibiotics, host genetics, and more.  Environmental factors cause perturbations in the biodiversity of the gut microbial communities occur throughout the lifecycle, however, the interplay between diet and host genetics determines the outcome: health or disease. Diabetes and obesity are complex chronic diseases that have reduced gut microbial biodiversity that contribute towards their pathophysiologies including insulin resistance, systemic inflammation, increased gut permeability, appetite dysregulation, distorted thermodynamics among other changes.  Bacteria causing weight gain are thought to induce the expression of genes related to lipid and carbohydrate metabolism thereby leading to greater energy harvest from the diet. Intricate fecal transplantation experiments in genetically manipulated mice have exquisitely demonstrated the interaction of genes and environment to produce metabolic outcomes that can either prevent to promote these chronic diseases. Novel therapies for these chronic diseases will be advanced by a deeper understanding of epigenetic modulation of host metabolism by the gut microbiome in health and in obesity and diabetes. 

In this Special Issue, we would like to invite submissions of original research or review articles on any topic related to “Diabetes, Obesity, and the Gut Microbiome”. We look forward to receiving your contributions.

Dr. Gerard E. Mullin
Prof. Laura Matarese
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Gut Microbiome
  • Obesity
  • Diabetes
  • Inflammation
  • Insulin resistance
  • Epigenetics
  • Animal Models
  • Probiotics
  • Prebiotics
  • Fecal transplantation

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Published Papers (7 papers)

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Research

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19 pages, 2617 KiB  
Article
Deciphering the Relationship between Obesity and Various Diseases from a Network Perspective
by Lei Chen, Yu-Hang Zhang, JiaRui Li, ShaoPeng Wang, YunHua Zhang, Tao Huang and Yu-Dong Cai
Genes 2017, 8(12), 392; https://doi.org/10.3390/genes8120392 - 18 Dec 2017
Cited by 8 | Viewed by 5796
Abstract
The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized [...] Read more.
The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized as the main reason for fat accumulation. Previous studies reported that obesity can be caused by the dysfunction of genes associated with other diseases, such as myocardial infarction, hence providing new insights into dissecting the pathogenesis of obesity by investigating its associations with other diseases. In this study, we investigated the relationship between obesity and diseases from Online Mendelian Inheritance in Man (OMIM) databases on the protein–protein interaction (PPI) network. The obesity genes and genes of one OMIM disease were mapped onto the network, and the interaction scores between the two gene sets were investigated on the basis of the PPI of individual gene pairs, thereby inferring the relationship between obesity and this disease. Results suggested that diseases related to nutrition and endocrine are the top two diseases that are closely associated with obesity. This finding is consistent with our general knowledge and indicates the reliability of our obtained results. Moreover, we inferred that diseases related to psychiatric factors and bone may also be highly related to obesity because the two diseases followed the diseases related to nutrition and endocrine according to our results. Numerous obesity–disease associations were identified in the literature to confirm the relationships between obesity and the aforementioned four diseases. These new results may help understand the underlying molecular mechanisms of obesity–disease co-occurrence and provide useful insights for disease prevention and intervention. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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11 pages, 6185 KiB  
Article
Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure, Composition and Predicted Metabolic Function
by Noel T. Mueller, Hakdong Shin, Aline Pizoni, Isabel C. Werlang, Ursula Matte, Marcelo Z. Goldani, Helena A. S. Goldani and Maria G. Dominguez-Bello
Genes 2017, 8(12), 364; https://doi.org/10.3390/genes8120364 - 4 Dec 2017
Cited by 54 | Viewed by 8071
Abstract
Cesarean (C-section) delivery, recently shown to cause excess weight gain in mice, perturbs human neonatal gut microbiota development due to the lack of natural mother-to-newborn transfer of microbes. Neonates excrete first the in-utero intestinal content (referred to as meconium) hours after birth, followed [...] Read more.
Cesarean (C-section) delivery, recently shown to cause excess weight gain in mice, perturbs human neonatal gut microbiota development due to the lack of natural mother-to-newborn transfer of microbes. Neonates excrete first the in-utero intestinal content (referred to as meconium) hours after birth, followed by intestinal contents reflective of extra-uterine exposure (referred to as transition stool) 2 to 3 days after birth. It is not clear when the effect of C-section on the neonatal gut microbiota emerges. We examined bacterial DNA in carefully-collected meconium, and the subsequent transitional stool, from 59 neonates [13 born by scheduled C-section and 46 born by vaginal delivery] in a private hospital in Brazil. Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced using the Illumina MiSeq (San Diego, CA, USA) platform. We found evidence of bacterial DNA in the majority of meconium samples in our study. The bacterial DNA structure (i.e., beta diversity) of meconium differed significantly from that of the transitional stool microbiota. There was a significant reduction in bacterial alpha diversity (e.g., number of observed bacterial species) and change in bacterial composition (e.g., reduced Proteobacteria) in the transition from meconium to stool. However, changes in predicted microbiota metabolic function from meconium to transitional stool were only observed in vaginally-delivered neonates. Within sample comparisons showed that delivery mode was significantly associated with bacterial structure, composition and predicted microbiota metabolic function in transitional-stool samples, but not in meconium samples. Specifically, compared to vaginally delivered neonates, the transitional stool of C-section delivered neonates had lower proportions of the genera Bacteroides, Parabacteroides and Clostridium. These differences led to C-section neonates having lower predicted abundance of microbial genes related to metabolism of amino and nucleotide sugars, and higher abundance of genes related to fatty-acid metabolism, amino-acid degradation and xenobiotics biodegradation. In summary, microbiota diversity was reduced in the transition from meconium to stool, and the association of delivery mode with microbiota structure, composition and predicted metabolic function was not observed until the passing of the transitional stool after meconium. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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12 pages, 1577 KiB  
Article
Genes and Gut Bacteria Involved in Luminal Butyrate Reduction Caused by Diet and Loperamide
by Nakwon Hwang, Taekil Eom, Sachin K. Gupta, Seong-Yeop Jeong, Do-Youn Jeong, Yong Sung Kim, Ji-Hoon Lee, Michael J. Sadowsky and Tatsuya Unno
Genes 2017, 8(12), 350; https://doi.org/10.3390/genes8120350 - 28 Nov 2017
Cited by 41 | Viewed by 6871
Abstract
Unbalanced dietary habits and gut dysmotility are causative factors in metabolic and functional gut disorders, including obesity, diabetes, and constipation. Reduction in luminal butyrate synthesis is known to be associated with gut dysbioses, and studies have suggested that restoring butyrate formation in the [...] Read more.
Unbalanced dietary habits and gut dysmotility are causative factors in metabolic and functional gut disorders, including obesity, diabetes, and constipation. Reduction in luminal butyrate synthesis is known to be associated with gut dysbioses, and studies have suggested that restoring butyrate formation in the colon may improve gut health. In contrast, shifts in different types of gut microbiota may inhibit luminal butyrate synthesis, requiring different treatments to restore colonic bacterial butyrate synthesis. We investigated the influence of high-fat diets (HFD) and low-fiber diets (LFD), and loperamide (LPM) administration, on key bacteria and genes involved in reduction of butyrate synthesis in mice. MiSeq-based microbiota analysis and HiSeq-based differential gene analysis indicated that different types of bacteria and genes were involved in butyrate metabolism in each treatment. Dietary modulation depleted butyrate kinase and phosphate butyryl transferase by decreasing members of the Bacteroidales and Parabacteroides. The HFD also depleted genes involved in succinate synthesis by decreasing Lactobacillus. The LFD and LPM treatments depleted genes involved in crotonoyl-CoA synthesis by decreasing Roseburia and Oscilllibacter. Taken together, our results suggest that different types of bacteria and genes were involved in gut dysbiosis, and that selected treatments may be needed depending on the cause of gut dysfunction. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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19 pages, 3463 KiB  
Article
Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats
by Jing-Hua Wang, Shambhunath Bose, Soo-Kyoung Lim, AbuZar Ansari, Young-Won Chin, Han Seok Choi and Hojun Kim
Genes 2017, 8(10), 239; https://doi.org/10.3390/genes8100239 - 22 Sep 2017
Cited by 33 | Viewed by 6715
Abstract
Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing [...] Read more.
Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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Review

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19 pages, 4322 KiB  
Review
Dietary Alteration of the Gut Microbiome and Its Impact on Weight and Fat Mass: A Systematic Review and Meta-Analysis
by George Kunnackal John, Lin Wang, Julie Nanavati, Claire Twose, Rajdeep Singh and Gerard Mullin
Genes 2018, 9(3), 167; https://doi.org/10.3390/genes9030167 - 16 Mar 2018
Cited by 120 | Viewed by 26830
Abstract
Dietary alteration of the gut microbiome is an important target in the treatment of obesity. Animal and human studies have shown bidirectional weight modulation based on the probiotic formulation used. In this study, we systematically reviewed the literature and performed a meta-analysis to [...] Read more.
Dietary alteration of the gut microbiome is an important target in the treatment of obesity. Animal and human studies have shown bidirectional weight modulation based on the probiotic formulation used. In this study, we systematically reviewed the literature and performed a meta-analysis to assess the impact of prebiotics, probiotics and synbiotics on body weight, body mass index (BMI) and fat mass in adult human subjects. We searched Medline (PubMed), Embase, the Cochrane Library and the Web of Science to identify 4721 articles, of which 41 were subjected to full-text screening, yielding 21 included studies with 33 study arms. Probiotic use was associated with significant decreases in BMI, weight and fat mass. Studies of subjects consuming prebiotics demonstrated a significant reduction in body weight, whereas synbiotics did not show an effect. Overall, when the utilization of gut microbiome-modulating dietary agents (prebiotic/probiotic/synbiotic) was compared to placebo, there were significant decreases in BMI, weight and fat mass. In summary, dietary agents for the modulation of the gut microbiome are essential tools in the treatment of obesity and can lead to significant decreases in BMI, weight and fat mass. Further studies are needed to identify the ideal dose and duration of supplementation and to assess the durability of this effect. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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16 pages, 444 KiB  
Review
Microbial Regulation of Glucose Metabolism and Insulin Resistance
by Silke Crommen and Marie-Christine Simon
Genes 2018, 9(1), 10; https://doi.org/10.3390/genes9010010 - 29 Dec 2017
Cited by 45 | Viewed by 9054
Abstract
Type 2 diabetes is a combined disease, resulting from a hyperglycemia and peripheral and hepatic insulin resistance. Recent data suggest that the gut microbiota is involved in diabetes development, altering metabolic processes including glucose and fatty acid metabolism. Thus, type 2 diabetes patients [...] Read more.
Type 2 diabetes is a combined disease, resulting from a hyperglycemia and peripheral and hepatic insulin resistance. Recent data suggest that the gut microbiota is involved in diabetes development, altering metabolic processes including glucose and fatty acid metabolism. Thus, type 2 diabetes patients show a microbial dysbiosis, with reduced butyrate-producing bacteria and elevated potential pathogens compared to metabolically healthy individuals. Furthermore, probiotics are a known tool to modulate the microbiota, having a therapeutic potential. Current literature will be discussed to elucidate the complex interaction of gut microbiota, intestinal permeability and inflammation leading to peripheral and hepatic insulin resistance. Therefore, this review aims to generate a deeper understanding of the underlying mechanism of potential microbial strains, which can be used as probiotics. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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12 pages, 226 KiB  
Review
Effects of Antidiabetic Drugs on Gut Microbiota Composition
by Sophie A. Montandon and François R. Jornayvaz
Genes 2017, 8(10), 250; https://doi.org/10.3390/genes8100250 - 30 Sep 2017
Cited by 113 | Viewed by 9065
Abstract
Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA); amino acids; bile acids or vitamins. It [...] Read more.
Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA); amino acids; bile acids or vitamins. It is becoming clear that gut microbiota is playing a prevalent role in pathologies such as metabolic syndrome; type 2 diabetes (T2D); inflammatory and bowel diseases. Obesity and related diseases; notably type 2 diabetes, induce gut dysbiosis. In this review; we aim to cover the current knowledge about the effects of antidiabetic drugs on gut microbiota diversity and composition as well as the potential beneficial effects mediated by specific taxa. Metformin is the first-line treatment against T2D. In addition to its glucose-lowering and insulin sensitizing effects, metformin promotes SCFA-producing and mucin-degrading bacteria. Other antidiabetic drugs discussed in this review show positive effects on dysbiosis; but without any consensus specifically regarding the Firmicutes to Bacteroidetes ratio. Thus, beneficial effects might be mediated by specific taxa. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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