Gut microbiome and microbial metabolites: a new system affecting metabolic disorders

2019 ◽  
Vol 42 (9) ◽  
pp. 1011-1018 ◽  
Author(s):  
M. Federici
2019 ◽  
Vol 8 (3) ◽  
pp. 317-332 ◽  
Author(s):  
Natalia Vallianou ◽  
Theodora Stratigou ◽  
Gerasimos Socrates Christodoulatos ◽  
Maria Dalamaga

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.


2021 ◽  
Author(s):  
Naoki Saji ◽  
Tsuyoshi Tsuduki ◽  
Kenta Murotani ◽  
Takayoshi Hisada ◽  
Taiki Sugimoto ◽  
...  

Abstract Background Previous studies have shown associations between the gut microbiota, microbial metabolites, and cognitive decline. However, the effect of the dietary composition on such associations has not been fully investigated. Methods We performed a cross-sectional sub-analysis of data from our prospective hospital-based cohort study (the Gimlet study) to evaluate the relationships between dietary composition, cognitive decline, and the gut microbiota. All the participants of the Gimlet study had been provided with information regarding this sub-study in 2018. Patients were excluded if they were unable to provide sufficient data in the questionnaire regarding their dietary composition. We assessed their demographics, dietary composition, risk factors, cognitive function, results of brain imaging, gut microbiome, and microbial metabolites. On the basis of previous studies, a nine-component traditional Japanese diet index (JDI9), a 12-component modern JDI (JDI12), and a 12-component revised JDI (rJDI12), were defined. Higher JDI scores indicated greater conformity to the traditional Japanese diet. We then evaluated the relationships between the JDI scores, cognitive function, and the gut microbiome and microbial metabolites using multivariable logistic regression analyses. Results We analyzed data from 85 eligible patients (61% women; mean age: 74.6 ± 7.4 years; mean Mini-Mental State Examination score: 24 ± 5). Compared with participants with dementia, those without dementia were more likely to consume foods in the JDI12, including fish and shellfish (64.5% vs. 39.1%, P = 0.048), mushrooms (61.3% vs. 30.4%, P = 0.015), soybeans and soybean-derived foods (62.9% vs. 30.4%, P = 0.013), and coffee (71.0% vs. 43.5%, P = 0.024). There were non-significant trends towards lower fecal concentrations of gut microbial metabolites in participants with a more traditional Japanese diet. Participants with dementia had lower JDI9, JDI12, and rJDI12 scores than participants without dementia (dementia vs. non-dementia, median JDI9 score: 5 vs. 7, P = 0.049; JDI12: 7 vs. 8, P = 0.017; and rJDI12: 7 vs. 9, P = 0.006, respectively). Conclusions Adherence to a traditional Japanese diet was found to be inversely associated with cognitive decline and tended to be associated with lower concentrations of gut microbial metabolites. Trial registration: UMIN000031851.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S041-S042
Author(s):  
V Svolos ◽  
K Gkikas ◽  
V Rizou ◽  
E Christina ◽  
P Kapranos ◽  
...  

Abstract Background Treatment with exclusive enteral nutrition (EEN) offers a nutritional therapy paradigm in Crohn’s disease, with the extensive modulation of gut microbiome being its proposed mechanism of action (1). Recent studies propose variable clinical efficacy for 85% EN (Cheat EN/CEN), 50% EN (Partial EN/PEN) and 20% EN (maintenance EN/MEN), and a dose-dependent effect of EN use in CD (2–5). Therefore, this study aims to investigate the dose-dependent effect of 100%, 85%, 50%, and 20% EN on faecal microbial metabolites; and to investigate if this effect can be used as a compliance marker for EEN. Methods Healthy adults followed EEN, CEN, PEN or MEN diet for 7 days. Fresh faecal samples were collected before and after each dietary intervention Dietary assessment was performed throughout the intervention using estimated weight food diaries. Faecal pH, water content, Bristol Stool Chart Score, short-chain fatty acids and hydrogen sulphide were measured. Results A total of 122 faecal samples were collected from 61 subjects. The Mean(SEM) EN intake for the four groups was EEN: 100(0), CEN: 85.6(0.5), PEN: 50.1(0.4), MEN: 19.9(0.2) % of total energy intake. The baseline levels of all faecal sample measures were no different between the four groups. Faecal water content, propionic acid and Bristol Stool Chart Score significantly decreased only during EEN (all p≤0.03). Faecal pH significantly increased during EEN, CEN and PEN (all p < 0.001), but not during MEN (p = 0.728). Faecal pH post-intervention was highest for EEN, followed by CEN and PEN [Mean(SEM), EEN: 8.2(0.1); CEN: 7.8(0.2); PEN: 7.3(0.1), all pairwise p ≤ 0.002]. The faecal concentration of hydrogen sulphide, acetic and butyric acid significantly decreased following both EEN and CEN groups (all p ≤ 0.009). The concentration of acetic acid post-EEN was significantly lower than the concentration post CEN [Mean(SEM), EEN: 173(10); CEN: 261(24) μmol/g, p = 0.001]. Hydrogen sulphide and butyric acid concentrations post EEN and post CEN were unchanged (p = 0.337, p = 0.141). Conclusion EEN extensively modulates faecal microbial metabolites and CEN induces similar effects. PEN induces variable effects and further analysis should investigate if variation in responses reflects differences in the non-EN food intake of the participants (50%). MEN had no effect on faecal microbial metabolites. Further analysis including high-throughput deep sequencing techniques will provide additional information about the dose-dependent effect of EN regimen on gut microbiome composition. References 1. Quince et al., Am J Gastroenterol, 110:1718–1729. 2. Logan et al., Aliment Pharmacol Ther, 2019;50:664–674. 3. Gupta et al., IBD, 2013;19:1374–1378. 4. Duncan et al., BMC Gastroenterol, 2014;14:50. 5. Lee et al., IBD, 2015;21:1786–1793.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing An ◽  
Junqi Wang ◽  
Li Guo ◽  
Yuan Xiao ◽  
Wenli Lu ◽  
...  

ObjectiveCatch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA.MethodsAn SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay.ResultsThe composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria.ConclusionLactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.


2019 ◽  
Vol 244 (6) ◽  
pp. 408-418 ◽  
Author(s):  
Tien S Dong ◽  
Jonathan P Jacobs

Over the last several years, a growing body of literature has linked the gut microbiome to human health and diseases such as obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). This paper will review the current literature investigating the influence of diets associated with metabolic disorders on the microbiome and how those changes promote susceptibility to metabolic disorders. It will then focus in-depth on the role of the gut microbiome in NAFLD. The review will highlight associations of microbial composition and function with progression of NAFLD in patients and discuss potential mechanisms that link the gut microbiome to NAFLD. Finally, it will address limitations of existing studies along with future directions for microbiome research in NAFLD, including potential microbe-related treatments. Impact statement This invited minireview for the upcoming thematic issue on the microbiome addresses the role of the microbiome in nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD has increased greatly in recent years in parallel with the rise in obesity and is now believed to have a population prevalence of 20–40%. It is anticipated to soon become the primary cause of liver-related morbidity and mortality, and unfortunately, there are few treatment options. Therefore, there is a critical need for improved understanding of NAFLD pathophysiology to provide new avenues for therapeutic intervention. In this paper, we have reviewed evidence from human and animal model studies that have associated microbiome composition and microbial metabolites with development and progression of NAFLD. We have also discussed proposed mechanisms by which the microbiome could contribute to NAFLD pathogenesis and addressed future directions for this field.


Author(s):  
Ifeanyi O. Oshim ◽  
Nneka R. Agbakoba ◽  
Evelyn U. Urama ◽  
Oluwayemisi Odeyemi ◽  
Nkechi A. Olise ◽  
...  

Microbiome that reside in the human gut are key contributors to host metabolism and are considered potential sources of novel therapeutics in metabolic disorders. This review discusses the role of gut microbiome in the pathogenesis of obesity, type 2 diabetes mellitus (T2DM), chronic kidney disease and cardiovascular disease. Gut microbiome remains quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understanding these changes is important to predict diseases and develop therapies. In gut heamostasis, Gut microbiome converts high fibres intake into short-chain fatty acids like butyrate, propionate and acetate which normalize intestinal permeability and alter de novo lipogenesis and gluconeogenesis through reduction of free fatty acid production by visceral adipose tissue. This effect contributes to reduce food intake and to improve glucose metabolism. Propionate can also bind to G protein coupled receptors (GPR)-43 expressed on lymphocytes in order to maintain appropriate immune defence. Butyrate activates peroxisome proliferator-activated receptor-γ (PPAR-γ) leading to beta-oxidation and oxygen consumption, a phenomenon contributing to maintain anaerobic condition in the gut lumen. In contrast, diets most especially western diet consisting among others of high fat and high salt content has been reported to cause gut dysbiosis. This alteration of gut microbiome result to chronic bacterial translocation and increased intestinal permeability that can drive a systemic inflammation leading to macrophage influx into visceral adipose tissue, activation of hepatic kuffer cells and insulin resistance in type 2 diabetes. This effect contributes to lower mucus thickness, decrease butyrate and propionate producing bacteria, L-cells secrete less gut peptides, lack of PPAR-γ activation lead to higher oxygen available for the microbiome at the proximity of the mucosa and increases the proliferation of Enterobacteriaceae with commensurate increase in opportunistic pathogens. However, Gut microbiome are major biomarker for early prognosis of diabetes and other metabolic disorders.


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