scholarly journals Commensal microbe-derived acetate suppresses NAFLD/NASH development via hepatic FFAR2 signalling in mice

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ryo Aoki ◽  
Masayoshi Onuki ◽  
Koya Hattori ◽  
Masato Ito ◽  
Takahiro Yamada ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiome ◽  
Resistant Starch ◽  
Short Chain Fatty Acids ◽  
Global Changes ◽  
Severe Liver ◽  
Acetate Production ◽  
Germ Free ◽  
Free Fatty Acid Receptor ◽  
Underlying Mechanisms

Abstract Background Non-alcoholic liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and it can progress to non-alcoholic steatohepatitis (NASH). Alterations in the gut microbiome have been implicated in the development of NAFLD/NASH, although the underlying mechanisms remain unclear. Results We found that the consumption of the prebiotic inulin markedly ameliorated the phenotype of NAFLD/NASH, including hepatic steatosis and fibrosis, in mice. Inulin consumption resulted in global changes in the gut microbiome, including concomitant enrichment of the genera Bacteroides and Blautia, and increased concentrations of short-chain fatty acids, particularly acetate, in the gut lumen and portal blood. The consumption of acetate-releasing resistant starch protected against NAFLD development. Colonisation by Bacteroides acidifaciens and Blautia producta in germ-free mice resulted in synergetic effects on acetate production from inulin. Furthermore, the absence of free fatty acid receptor 2 (FFAR2), an acetate receptor, abolished the protective effect of inulin, as indicated by the more severe liver hypertrophy, hypercholesterolaemia and inflammation. These effects can be attributed to an exacerbation of insulin resistance in the liver, but not in muscle or adipose tissue. Conclusion These findings demonstrated that the commensal microbiome–acetate–FFAR2 molecular circuit improves insulin sensitivity in the liver and prevents the development of NAFLD/NASH.

scholarly journals Gut Microbial Composition in Mice Fed Different Amount of Rice Resistant Starch (P21-031-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jiawei Wan ◽  
Yanbei Wu ◽  
Quynhchi Pham ◽  
Robert Li ◽  
Liangli Yu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Resistant Starch ◽  
Operational Taxonomic Unit ◽  
Short Chain Fatty Acids ◽  
High Fat ◽  
Low Fat ◽  
Microbial Composition ◽  
Rdna Sequencing ◽  
Different Levels ◽  
Starch Diet

Abstract Objectives The aim of this study is to evaluate the effects of rice containing different levels of resistant starch on the gut microbiome using a rodent model. Methods Rice with low resistant starch (0.11%), medium resistant starch (1.07%) and high resistant starch (8.61%) were cooked, grounded into powders and used to formulate diet to represent all the carbohydrates in mice diet that consist of low fat (LF, 10 kcal %) or high fat (HF, 39 kcal %). C57BL/6 mice (n = 60, male, 5 weeks old) were randomly assigned to six feeding groups: (1) low-fat and low resistant starch diet (LL); (2) high-fat and low resistant starch diet (HL); (3) low-fat and medium resistant starch diet (LM); (4) high-fat and medium resistant starch diet (HM); (5) low-fat and high resistant starch diet (LH); (6) high-fat and high resistant starch diet (HH). Mice were fed with diets for 8 weeks then gut microbiome composition was determined using 16S rDNA sequencing of cecal contents. Results We found that the gut microbiome was significantly different at different levels of resistant starch (P < 0.01) but not at different fat levels. OTU (operational taxonomic unit) richness was reduced in LF and HF high-resistant groups as compared to others. OTU diversity was reduced in LF and HF medium and high-resistant groups as compared to low-resistant groups. Decreased Firmicutes to Bacteroidetes ratio, which related to lower risk of obesity, was observed in mice fed LF and HF high-resistant diet as compared to others. Moreover, at the family level, LF, HF high-resistant diet mainly increased the abundances of Bacteroidaceae and S24_7, the bacteria positively correlated with SCFAs (short-chain fatty acids) levels. We also observed a decrease in abundances of Odoribacteraceae, Rikenellaceae, Lachnospiraceae, Ruminococcaceae and Desulfovibrionaceae in LF and HF high resistant starch group. Desulfovibrionaceae and genus Odoribecter in Odoribacteraceae are reported to be opportunistic pathogens, Lachnospiraceae, Ruminococcaceae, Odoribacteraceae and Rikenellaceae are associated with obesity. Conclusions Overall, our results demonstrated that resistant starch exerted concentration-dependent effect on the gut microbiome in mice which may have protective effect against obesity. Funding Sources USDA, ARS.

scholarly journals High-fructose feeding suppresses cold-stimulated brown adipose tissue glucose uptake in young men independently of changes in thermogenesis and the gut microbiome

2022 ◽  
Author(s):  
Gabriel Richard ◽  
Denis P. Blondin ◽  
Saad A. Syed ◽  
Laura Rossi ◽  
Michelle E. Fontes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
High Glucose ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Short Chain Fatty Acids ◽  
Alcoholic Fatty Liver ◽  
High Fructose ◽  
Brown Adipose

Diets rich in added sugars, especially high in fructose, are associated with metabolic diseases such as insulin resistance, and non-alcoholic fatty liver disease. Studies have shown a link between these pathologies and changes in the microbiome and its metabolites. Given the reported associations in animal models between the microbiome and brown or beige adipose tissue (BAT) function, and the alterations in the microbiome induced by high glucose or high fructose diets, we investigated the potential causal link between high glucose or fructose diets and BAT dysfunction in humans. We show that BAT glucose uptake, but not thermogenesis, is impaired by a high fructose but not high glucose diet, in the absence of changes in body mass, the gastrointestinal microbiome, and faecal short-chain fatty acids. We conclude that BAT metabolic dysfunction occurs independently from changes in gut microbiome composition, and earlier than other pathophysiological abnormalities associated with insulin resistance and dyslipidemia during fructose overconsumption in humans.

scholarly journals Ecological dynamics of the gut microbiome in response to dietary fiber

2021 ◽  
Author(s):  
Hongbin Liu ◽  
Chen Liao ◽  
Jinhui Tang ◽  
Junyu Chen ◽  
Chaobi Lei ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Resistant Starch ◽  
Short Chain Fatty Acids ◽  
Metabolic Function ◽  
Fiber Intake ◽  
Learning Models ◽  
Interspecies Competition ◽  
Gradual Stabilization ◽  
Machine Learning Models

Dietary fibers are generally thought to benefit intestinal health. Their impacts on the composition and metabolic function of the gut microbiome, however, vary greatly across individuals. Previous research showed that each individual's response to fibers depends on their baseline gut microbiome, but the ecology driving microbiota remodeling during fiber intake remained unclear. Here, we studied the long-term dynamics of gut microbiome and short-chain fatty acids (SCFAs) in isogenic mice with distinct microbiota baselines fed with the fermentable fiber inulin compared to the non-fermentable fiber cellulose. We found that inulin produced generally rapid response followed by gradual stabilization to new equilibria, and those dynamics were baseline-dependent. We parameterized an ecology model from the timeseries data, which revealed a group of bacteria whose growth significantly increases in response to inulin. and whose baseline abundance and interspecies competition explains the baseline-dependence of microbiome density and community composition dynamics. Fecal levels of of SCFAs, such as propionate, is associated with the abundance of inulin responders, yet inter-individual variation of gut microbiome impedes the prediction of SCFAs by machine learning models. Finally, we showed that our methods and major findings are generalizable to dietary resistant starch. This study emphasizes the importance of ecological modeling to understand microbiome responses to dietary changes and the need for personalized interventions.

scholarly journals Roux-en-Y Gastric Bypass Improved Insulin Resistance via Alteration of the Human Gut Microbiome and Alleviation of Endotoxemia

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Qiping Shi ◽  
Qian Wang ◽  
Hui Zhong ◽  
Dehai Li ◽  
Shuxing Yu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gastric Bypass ◽  
Gut Microbiota ◽  
Serum Levels ◽  
Short Chain Fatty Acids ◽  
Underlying Mechanism ◽  
Postoperative Time ◽  
Obese Subjects ◽  
Underlying Mechanisms

Background. Obesity is a main contributing factor for the development of glucose intolerance and type 2 diabetes mellitus (T2D). Roux-en-Y gastric bypass (RYGB) is believed to be one of the most effective treatments to reduce body weight and improve glucose metabolism. In this study, we sought to explore the underlying mechanisms of weight reduction and insulin resistance improvement after RYGB. Methods. This was a prospective observational study using consecutive samples of 14 obese subjects undergoing bariatric surgery. Main assessments were serum indexes (blood metabolites, glucose-lipid regulating hormones, trimethylamine-N-oxide (TMAO), and lipopolysaccharide-binding protein (LBP), fecal short-chain fatty acids (SCFAs), and gut microbiota. Correlation analysis of the factors changed by RYGB was used to indicate the potential mechanism by which surgery improves insulin resistance. Results. The subjects showed significant improvement on indices of obesity and insulin resistance and a correlated change of gut microbiota components at 1 month, 3 months, and 6 months post-RYGB operation. In particular, the abundance of a counterobese strain, Akkemansia muciniphila, had gradually increased with the postoperative time. Moreover, these changes were negatively correlated to serum levels of LBP and positively correlated to serum TMAO and fecal SCFAs. Conclusions. Our findings uncovered links between intestinal microbiota alterations, circulating endotoxemia, and insulin resistance. This suggests that the underlying mechanism of protection of the intestine by RYGB in obesity may be through changing the gut microbiota.

scholarly journals Influence of branched chain amino acids on insulin sensitivity and the mediator roles of short chain fatty acids and gut hormones: a review

2018 ◽  
Vol 2 ◽  
Author(s):  
Akram Abolbaghaei ◽  
B. Dave Oomah ◽  
Hamed Tavakoli ◽  
Farah Hosseinian
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Hormone Secretion ◽  
Short Chain Fatty Acids ◽  
Branched Chain Amino Acids ◽  
Branched Chain

Circulating levels of branched chain amino acids (BCAAs) correlate strongly with type 2 diabetes (T2D). The correlation may be associated with insulin-resistance factors independent of glycemic markers currently used in the diagnosis and monitoring of diabetes. This can revolutionize the thought process and methodology not only in diabetes treatment, but also in its advance screening and prevention with BCAAs used as biomarkers and targets for treatment. Whether insulin resistance is the cause or result of BCAAs imbalances requires further investigation. Although the overall diet is important, the role of specific diets targeting the gut microbiome composition and hormone secretion affecting BCAA absorption and metabolism will be explored. Generic diet modifications apparently induce only negligible changes in the intrinsic genetic make-up of the gut and BCAA levels but influence specific modulation of the gut microbiome. This genetic make-up is indeed similar among T2D patients independent of numerous variables including obesity. Short-chain fatty acids (SCFAs), the primary end-products of non-digestible carbohydrates (NDC) fermentation, mediate metabolic imbalances through gut microbiota and gut hormone secretion. This review focuses on extensive evidence gathered using diverse methodologies on the strong parallel correlation between BCAA levels and insulin resistance. Furthermore, the role of specific diets particularly SCFAs as mediators of the stubbornly fixed intrinsic genetic make-up of gut microbiota will be scrutinized to delineate BCAA levels and insulin resistance in T2D.

scholarly journals FFAR from the Gut Microbiome Crowd: SCFA Receptors in T1D Pathology

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 302
Author(s):  
Medha Priyadarshini ◽  
Kristen Lednovich ◽  
Kai Xu ◽  
Sophie Gough ◽  
Barton Wicksteed ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Review Article ◽  
Microbial Metabolites ◽  
Novel Treatments ◽  
Metabolic Conditions ◽  
Underlying Mechanisms

The gut microbiome has emerged as a novel determinant of type 1 diabetes (T1D), but the underlying mechanisms are unknown. In this context, major gut microbial metabolites, short-chain fatty acids (SCFAs), are considered to be an important link between the host and gut microbiome. We, along with other laboratories, have explored how SCFAs and their cognate receptors affect various metabolic conditions, including obesity, type 2 diabetes, and metabolic syndrome. Though gut microbiome and SCFA-level changes have been reported in T1D and in mouse models of the disease, the role of SCFA receptors in T1D remains under explored. In this review article, we will highlight the existing and possible roles of these receptors in T1D pathology. We conclude with a discussion of SCFA receptors as therapeutic targets for T1D, exploring an exciting new potential for novel treatments of glucometabolic disorders.

Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunmin Park ◽  
Sunna Kang ◽  
Da Sol Kim
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Insulin Signaling ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Memory Function ◽  
Amyloid Β ◽  
Impaired Memory ◽  
Ca1 Region ◽  
Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

Associations between gut microbiome, short chain fatty acids and blood pressure across ethnic groups: the HELIUS study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Verhaar ◽  
D Collard ◽  
A Prodan ◽  
J.H.M Levels ◽  
A.H Zwinderman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Ethnic Groups ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Funding Source ◽  
Microbiome Composition ◽  
Helius Study ◽  
Chain Fatty Acids

Abstract Background Gut microbiome composition is shaped by a combination of host genetic make-up and dietary habits. In addition, large ethnic differences exist in microbiome composition. Several studies in humans and animals have shown that differences in gut microbiota and its metabolites, including short chain fatty acids (SCFA), are associated with blood pressure (BP). We hypothesized that gut microbiome composition and its metabolites may be differently associated with BP across ethnic groups. Purpose To investigate associations of gut microbiome composition and fecal SCFA levels with BP across different ethnic groups. Methods We assessed the association between gut microbiome composition and office BP among 4672 subjects (mean age 49.8±11.7 years, 52%F) of 6 different ethnic groups participating in the HELIUS study. Gut microbiome composition was determined using 16S rRNA sequencing. Associations between microbiome composition and blood pressure were assessed using machine learning prediction models. The resulting best predictors were correlated with BP using Spearman's rank correlations. Fecal SCFA levels were measured with high-performance liquid chromatography in an age- and body mass index (BMI)-matched subgroup of 200 participants with either extreme low or high systolic BP. Differences in abundances of best predictors and fecal SCFA levels between high and low BP groups were assessed with Mann-Whitney U tests. Results Gut microbiome composition explained 4.4% of systolic BP variance. Best predictors for systolic BP included Roseburia spp. (ρ −0.15, p&lt;0.001), Clostridium spp. (ρ −0.14, p&lt;0.001), Romboutsia spp. (ρ −0.10, p&lt;0.001), and Ruminococceae spp. (ρ −0.15, p&lt;0.001) (Figure 1). Explained variance of the microbiome composition was highest in Dutch subjects (4.8%), but very low in African Surinamese, Ghanaian, and Turkish ethnic groups (ranging from 0–0.77%) Hence, we selected only participants with Dutch ethnicity for the matched subgroup. Participants with high BP had lower abundance of Roseburia hominis (p&lt;0.01) and Roseburia spp. (p&lt;0.05) compared to participants with low BP. However, fecal acetate (p&lt;0.05) and propionate (p&lt;0.01) levels were higher in participants with high BP. Conclusions In this cross-sectional study, gut microbiome composition was moderately associated with BP. Associations were strongly divergent between ethnic groups, with strongest associations in Dutch participants. Intriguingly, while Dutch participants with high BP had lower abundances of several SCFA-producing microbes, they had higher fecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD Amsterdam) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013) and the European Union (Seventh Framework Programme, FP-7; grant no. 278901).

Gut microbiome–short-chain fatty acids interplay in the context of iron deficiency anaemia

2021 ◽  
Author(s):  
Ana Soriano-Lerma ◽  
María García-Burgos ◽  
María J.M. Alférez ◽  
Virginia Pérez-Carrasco ◽  
Victoria Sanchez-Martin ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Iron Deficiency ◽  
Gut Microbiome ◽  
Iron Deficiency Anaemia ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Deficiency Anaemia ◽  
Chain Fatty Acids

scholarly journals γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut–Microbiome–Brain Axis

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Do-Youn Jeong ◽  
Myeong Seon Ryu ◽  
Hee-Jong Yang ◽  
Sunmin Park
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Gut Microbiome ◽  
Memory Impairment ◽  
Memory Function ◽  
Bacillus Species ◽  
Fermented Foods ◽  
Short Term ◽  
Brain Insulin ◽  
Brain Insulin Resistance

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24–72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut–microbiome–brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer’s disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20–30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut–microbiome–brain axis.

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