Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Heianza, Yoriko; Sun, Dianjianyi; Li, Xiang; DiDonato, Joseph A.; Bray, George A.; Sacks, Frank M.; Qi, Lü

doi:10.1136/gutjnl-2018-316155

Cited by 141 publications

(98 citation statements)

References 52 publications

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“…The POUNDS Lost Trial included 510 overweight and obese individuals exposed to a low-calorie diet for two years and found that a decrease in choline and l -carnitine levels was significantly related to weight loss, indicating it might serve as a predictive marker of response to weight-loss treatment [ 58 , 59 , 60 ]. The same study documented a significant improvement in IR associated with decreases in choline and l -carnitine [ 61 ]. Moreover, non-esterified fatty acids are known to induce IR and thus impair β-cell function [ 62 ].…”

Section: Epigenetics Microbiota and T2dmmentioning

confidence: 99%

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

et al. 2019

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Purpose of Review The metabolic syndrome is a pathological state in which one of the key components is insulin resistance. A wide spectrum of body compartments is involved in its pathophysiology. Genetic and environmental factors such as diet and physical activity are both related to its etiology. Reversible modulation of gene expression without altering the DNA sequence, known as epigenetic modifications, has been shown to drive this complex metabolic cluster of conditions. Here, we aim to examine some of the recent research of specific epigenetically mediated mechanisms and microbiota-induced epigenetic modifications on the development of adipose tissue and obesity, β-cell dysfunction and diabetes, and hepatocytes and non-alcoholic fatty disease. Recent Findings DNA methylation patterns and histone modifications have been identified in this context; the integrated analysis of genome, epigenome, and transcriptome is likely to expand our knowledge of epigenetics in health and disease. Epigenetic modifications induced by diet-related microbiota or metabolites possibly contribute to the insulin-resistant state. Summary The identification of epigenetic signatures on diabetes and obesity may give us the possibility of developing new interventions, prevention measures, and follow-up strategies.

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Section: Epigenetics Microbiota and T2dmmentioning

confidence: 99%

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

et al. 2019

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“…Trimethylamine N-oxide (TMAO) is a bacterial-derived metabolite that has been strongly associated with cardiovascular risks in both human and animal studies 162,[169][170][171] . Choline and l-carnitine are the major precursors of TMAO, and they are highly abundant in the Western diet, which is rich in red meat, dairy products, eggs and fish (Fig.…”

Section: Specific Drugs To Alter Microbial Metabolismmentioning

confidence: 99%

Microbial regulation of organismal energy homeostasis

et al. 2019

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Facts and figures on the gut microbiota The term microbiota refers to all the microorganisms present in the various ecosystems in the human body. Diverse communities of microorganisms are located throughout the human body, including the gut, lungs, vaginal and urinary tracts and skin. The microbiota is composed of several types of microbes: bacteria, archaea, viruses, phages, yeast and fungi 1. Humans have constantly coevolved in the presence of these microorganisms, thereby establishing symbiotic relationships. Several lines of evidence suggest that in addition to bacteria, other types of microbes, such as fungi, protozoa and viruses, also have important interactions with the human in which they reside, referred to as the host in this review 2,3. Nevertheless, interactions between bacteria and human cells have been studied the most and will be the focus of this review. The human body carries approximately 3.9 × 10 13 bacterial cells, with the largest amount residing in the large intestine: 10 11 bacteria cells g-1 of wet stool 4. At the most recent estimation, almost 10 million non-redundant microbial genes have been identified in the human gut 5. This number is 150-fold higher than the number of genes in the human genome 6. Therefore, the metabolic capacity of the gut microbiota greatly exceeds the metabolic capacity of human cells. The theory of energy harvest Pioneering studies linking SCFAs and energy harvest. The complex and dynamic ecosystem of the gut microbiota contributes to the metabolism of various compounds, thereby leading to the production of numerous metabolites. In the early 2000s, pioneering studies from Gordon and colleagues 11 linked the production of specific metabolites, such as short-chain fatty acids (SCFAs), to host energy homeostasis (Table 1). Bäckhed et al. 12 demonstrated the role of the gut microbiota in host energy metabolism and growth by showing that germ-free mice gained less body weight and fat mass than conventionalised mice (that is, those harbouring a gut microbiota). This difference was observed despite increased food intake in germ-free mice. The same group of researchers found that the microbiota of genetic obese mice (ob/ob) harvests more energy than their lean ob/+ counterparts. In addition, this phenotype was transferred in germ-free mice transplanted with the microbiota from the obese donors 11. Initially, the hypothesis was that this shift provided more SCFAs (acetate, propionate, butyrate and lactate) that could be used as metabolic substrates by the host (Fig. 1). In addition, it was suggested that the gut microbiota contributed to energy metabolism through a direct interaction with the digestive tract. Indeed, the germ-free mice exhibit a lower level of caecal SCFAs than

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“…The intestinal barrier is considered a functional, immunological, and anatomical unit, separating the intestinal lumen from circulating blood, preventing bacterial adherence and transport regulation. Methanolamine and other intestinal metabolites reach almost all tissues as small molecules thus affecting both neurohormonal and peripheral regulatory mechanisms [ 17 ].…”

Section: Microbiome Compositionmentioning

confidence: 99%

Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications

Leustean

Ciocoiu

Sava

et al. 2018

Journal of Diabetes Research

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The prevalence of diabetes is steadily rising, and once it occurs, it can cause multiple complications with a negative impact on the whole organism. Complications of diabetes may be macrovascular: such as stroke and ischemic heart disease as well as peripheral vascular and microvascular diseases—retinopathy, nephropathy, and neuropathy. Key factors that cause cardiovascular disease in people with diabetes include hyperglycemia, dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and decreased vascular response capacity. Microbes can be considered a complex endocrine system capable of ensuring the proper functioning of the body but are also responsible for the development of numerous pathologies (diabetes, coronary syndromes, peripheral arterial disease, neoplasia, Alzheimer's disease, and hepatic steatosis). Changes in the intestinal microbiota may influence the host's sensitivity to insulin, body weight, and lipid and carbohydrate metabolism. Dysbiosis causes activation of proinflammatory mechanisms, metabolic toxicity, and insulin resistance. Trimethylamine N-oxide (TMAO) is a microbial organic compound generated by the large intestine, and its concentration increases in the blood after ingestion of foods rich in L-carnitine and choline, such as red meat, eggs, and fish. The interest for TMAO in cardiometabolic research has recently emerged, given the preclinical evidence that reveals a link between TMAO, diabetes, and cardiovascular complications. Intestinal microbiota can be modulated by changing one's lifestyle but also by antibiotic, probiotic, prebiotic, and fecal transplantation. The purpose of this article is to highlight issues related to the involvement of microbiota and trimethylamine N-oxide in the pathogenesis of diabetes mellitus and cardiovascular disease. Better appreciation of the interactions between food intake and intestinal floral-mediated metabolism can provide clinical insights into the definition of individuals with diabetic risk and cardiometabolic disease as well as potential therapeutic targets for reducing the risk of progression of the disease.

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Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial

Cited by 141 publications

References 52 publications

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease

Microbial regulation of organismal energy homeostasis

Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications

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