scholarly journals Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism

2020 ◽  
Vol 6 (1) ◽  
pp. eaax6208 ◽  
Author(s):  
Su-Ling Zeng ◽  
Shang-Zhen Li ◽  
Ping-Ting Xiao ◽  
Yuan-Yuan Cai ◽  
Chu Chu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Amplicon Sequencing ◽  
Therapeutic Interventions ◽  
Protective Effects ◽  
Fecal Microbiome ◽  
Metabolomic Profiling ◽  
Branched Chain

Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)–induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.

scholarly journals Glucagon Receptor Signaling and Glucagon Resistance

2019 ◽  
Vol 20 (13) ◽  
pp. 3314 ◽  
Author(s):  
Janah ◽  
Kjeldsen ◽  
Galsgaard ◽  
Winther-Sørensen ◽  
Stojanovska ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Diseases ◽  
Physiological Role ◽  
Glucagon Receptor ◽  
Metabolomic Profiling ◽  
Hepatic Fat

Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). The suggested key role of glucagon in the development of diabetes has been termed the bihormonal hypothesis. However, studying tissue-specific knockout of the glucagon receptor has revealed that the physiological role of glucagon may extend beyond blood-glucose regulation. Decades ago, animal and human studies reported an important role of glucagon in amino acid metabolism through ureagenesis. Using modern technologies such as metabolomic profiling, knowledge about the effects of glucagon on amino acid metabolism has been expanded and the mechanisms involved further delineated. Glucagon receptor antagonists have indirectly put focus on glucagon’s potential role in lipid metabolism, as individuals treated with these antagonists showed dyslipidemia and increased hepatic fat. One emerging field in glucagon biology now seems to include the concept of hepatic glucagon resistance. Here, we discuss the roles of glucagon in glucose homeostasis, amino acid metabolism, and lipid metabolism and present speculations on the molecular pathways causing and associating with postulated hepatic glucagon resistance.

scholarly journals Dietary casein, egg albumin, and branched-chain amino acids attenuate phosphate-induced renal tubulointerstitial injury in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Karin Shimada ◽  
Isao Matsui ◽  
Kazunori Inoue ◽  
Ayumi Matsumoto ◽  
Seiichi Yasuda ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Muscle Weakness ◽  
Branched Chain Amino Acids ◽  
Protective Effects ◽  
Egg Albumin ◽  
Branched Chain Amino Acid ◽  
Renal Tubulointerstitial Fibrosis ◽  
Dietary Casein ◽  
Branched Chain

Abstract Dietary phosphate intake is closely correlated with protein intake. However, the effects of the latter on phosphate-induced organ injuries remain uncertain. Herein, we investigated the effects of low (10.8%), moderate (23.0%), and high (35.2%) dietary casein and egg albumin administration on phosphate-induced organ injuries in rats. The moderate and high casein levels suppressed renal tubulointerstitial fibrosis and maintained mitochondrial integrity in the kidney. The serum creatinine levels were suppressed only in the high casein group. Phosphate-induced muscle weakness was also ameliorated by high dietary casein. The urinary and fecal phosphate levels in the early experiment stage showed that dietary casein did not affect phosphate absorption from the intestine. High dietary egg albumin showed similar kidney protective effects, while the egg albumin effects on muscle weakness were only marginally significant. As the plasma branched-chain amino acid levels were elevated in casein- and egg albumin-fed rats, we analyzed their effects. Dietary supplementation of 10% branched-chain amino acids suppressed phosphate-induced kidney injury and muscle weakness. Although dietary protein restriction is recommended in cases of chronic kidney disease, our findings indicate that the dietary casein, egg albumin, and branched-chain amino acid effects might be reconsidered in the era of a phosphate-enriched diet.

scholarly journals Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mice

2018 ◽  
Vol 315 (4) ◽  
pp. E511-E519 ◽  
Author(s):  
Ty T. Kim ◽  
Nirmal Parajuli ◽  
Miranda M. Sung ◽  
Suresh C. Bairwa ◽  
Jody Levasseur ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Glucose Homeostasis ◽  
Intestinal Inflammation ◽  
Obese Mice ◽  
Fecal Transplant ◽  
Fecal Microbiome ◽  
Oral Supplementation ◽  
Beneficial Effects ◽  
The Metabolic Syndrome

Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome.

scholarly journals Male castration alters the gut microbiota, leading to increased serum levels of branched-chain amino acids and adiposity

2019 ◽  
Author(s):  
Tae Woong Whon ◽  
Hyun Sik Kim ◽  
Na-Ri Shin ◽  
Eun Sung Jung ◽  
Euon Jung Tak ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Branched Chain Amino Acids ◽  
Metabolic Phenotype ◽  
Male Hypogonadism ◽  
Branched Chain ◽  
Host Metabolism

Abstract Background: Testosterone deficiency is positively correlated with fat accumulation and obesity-related comorbidities, such as metabolic syndrome. Castration of young males is widely used in the cattle industry to improve meat quality. However, the mechanism linking hypogonadism and host metabolism is not clear. We aimed to evaluate the effect of male hypogonadism on the gut microbiota and serum metabolites, and the contribution of the altered microbiota to the host metabolic phenotype during hypogonadism. Results: We used metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. We then used a male mouse castration model to evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. After pubescence, the CtM cattle harbored distinct ileal microbiota dominated by the family Peptostreptococcaceae, and exhibited distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. Castration of male mice phenocopied both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model further revealed that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Conclusions: We demonstrated altered gut microbial profiles in the hypogonadal animals, with a negative feedback between the serum testosterone levels and the ileal abundance of Peptostreptococcaceae, and a distinct metabolic phenotype, with an enhanced amino acid metabolism. These findings suggest targeting the gut microbiota as a potential therapeutic strategy for the treatment of both hypogonadism and obesity.

scholarly journals Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhongmei Sun ◽  
Junxiang Li ◽  
Wenting Wang ◽  
Yuyue Liu ◽  
Jia Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Mucosal Healing ◽  
Intestinal Stem Cells ◽  
Mucosal Inflammation ◽  
Protective Effects ◽  
Fecal Microbiome ◽  
Epithelial Regeneration

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

scholarly journals Distinct Gut Microbiota Induced by Different Fat-to-Sugar-Ratio High-Energy Diets Share Similar Pro-obesity Genetic and Metabolite Profiles in Prediabetic Mice

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Kai Shan ◽  
Hongyan Qu ◽  
Keru Zhou ◽  
Liangfang Wang ◽  
Congmin Zhu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Early Stage ◽  
Amplicon Sequencing ◽  
High Energy ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients

ABSTRACT Gut microbiota play important roles in host metabolism, especially in diabetes. However, why different diets lead to similar diabetic states despite being associated with different microbiota is not clear. Mice were fed two high-energy diets (HED) with the same energy density but different fat-to-sugar ratios to determine the associations between the microbiota and early-stage metabolic syndrome. The two diets resulted in different microbiota but similar diabetic states. Interestingly, the microbial gene profiles were not significantly different, and many common metabolites were identified, including l-aspartic acid, cholestan-3-ol (5β, 3α), and campesterol, which have been associated with lipogenesis and inflammation. Our study suggests that different metabolic-syndrome-inducing diets may result in different microbiota but similar microbiomes and metabolomes. This suggests that the metagenome and metabolome are crucial for the prognosis and pathogenesis of obesity and metabolic syndrome. IMPORTANCE Various types of diet can lead to type 2 diabetes. The gut microbiota in type 2 diabetic patients are also different. So, two questions arise: whether there are any commonalities between gut microbiota induced by different pro-obese diets and whether these commonalities lead to disease. Here we found that high-energy diets with two different fat-to-sugar ratios can both cause obesity and prediabetes but enrich different gut microbiota. Still, these different gut microbiota have similar genetic and metabolite compositions. The microbial metabolites in common between the diets modulate lipid accumulation and macrophage inflammation in vivo and in vitro. This work suggests that studies that only use 16S rRNA amplicon sequencing to determine how the microbes respond to diet and associate with diabetic state are missing vital information.

scholarly journals Vegan Diet Is Associated With Favorable Effects on the Metabolic Performance of Intestinal Microbiota: A Cross-Sectional Multi-Omics Study

2022 ◽  
Vol 8 ◽  
Author(s):  
Magdalena Prochazkova ◽  
Eva Budinska ◽  
Marek Kuzma ◽  
Helena Pelantova ◽  
Jaromir Hradecky ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gut Microbiota ◽  
Lithocholic Acid ◽  
Metabolic Health ◽  
Vegan Diet ◽  
Acid Fermentation ◽  
Cross Sectional ◽  
Potential Health ◽  
Fermentation Products ◽  
Fecal Microbiome

Background and Aim: Plant-based diets are associated with potential health benefits, but the contribution of gut microbiota remains to be clarified. We aimed to identify differences in key features of microbiome composition and function with relevance to metabolic health in individuals adhering to a vegan vs. omnivore diet.Methods: This cross-sectional study involved lean, healthy vegans (n = 62) and omnivore (n = 33) subjects. We assessed their glucose and lipid metabolism and employed an integrated multi-omics approach (16S rRNA sequencing, metabolomics profiling) to compare dietary intake, metabolic health, gut microbiome, and fecal, serum, and urine metabolomes.Results: The vegans had more favorable glucose and lipid homeostasis profiles than the omnivores. Long-term reported adherence to a vegan diet affected only 14.8% of all detected bacterial genera in fecal microbiome. However, significant differences in vegan and omnivore metabolomes were observed. In feces, 43.3% of all identified metabolites were significantly different between the vegans and omnivores, such as amino acid fermentation products p-cresol, scatole, indole, methional (lower in the vegans), and polysaccharide fermentation product short- and medium-chain fatty acids (SCFAs, MCFAs), and their derivatives (higher in the vegans). Vegan serum metabolome differed markedly from the omnivores (55.8% of all metabolites), especially in amino acid composition, such as low BCAAs, high SCFAs (formic-, acetic-, propionic-, butyric acids), and dimethylsulfone, the latter two being potential host microbiome co-metabolites. Using a machine-learning approach, we tested the discriminative power of each dataset. Best results were obtained for serum metabolome (accuracy rate 91.6%).Conclusion: While only small differences in the gut microbiota were found between the groups, their metabolic activity differed substantially. In particular, we observed a significantly different abundance of fermentation products associated with protein and carbohydrate intakes in the vegans. Vegans had significantly lower abundances of potentially harmful (such as p-cresol, lithocholic acid, BCAAs, aromatic compounds, etc.) and higher occurrence of potentially beneficial metabolites (SCFAs and their derivatives).

scholarly journals Male castration alters the gut microbiota, leading to increased serum levels of branched-chain amino acids and adiposity

2020 ◽  
Author(s):  
Tae Woong Whon ◽  
Hyun Sik Kim ◽  
Na-Ri Shin ◽  
Eun Sung Jung ◽  
Euon Jung Tak ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Branched Chain Amino Acids ◽  
Metabolic Phenotype ◽  
Male Hypogonadism ◽  
Branched Chain ◽  
Host Metabolism

Abstract Background : Testosterone deficiency is positively correlated with fat accumulation and obesity-related comorbidities, such as metabolic syndrome. Castration of young males is widely used in the cattle industry to improve meat quality. However, the mechanism linking hypogonadism and host metabolism is not clear. We aimed to evaluate the effect of male hypogonadism on the gut microbiota and serum metabolites, and the contribution of the altered microbiota to the host metabolic phenotype during hypogonadism.Results : We used metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. We then used a male mouse castration model to evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. After pubescence, the CtM cattle harbored distinct ileal microbiota dominated by the family Peptostreptococcaceae , and exhibited distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. Castration of male mice phenocopied both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model further revealed that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals.Conclusions : We demonstrated altered gut microbial profiles in the hypogonadal animals, with a negative feedback between the serum testosterone levels and the ileal abundance of Peptostreptococcaceae , and a distinct metabolic phenotype, with an enhanced amino acid metabolism. These findings suggest targeting the gut microbiota as a potential therapeutic strategy for the treatment of both hypogonadism and obesity.

scholarly journals Metabolic disorders and gut microbiota

2020 ◽  
Vol 15 (3) ◽  
pp. 177-183
Author(s):  
Anna Kotrova ◽  
◽  
Alexandr Shishkin ◽  
Maria Lukashenko ◽  
◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Sensitivity ◽  
Gut Microbiota ◽  
Carbohydrate Metabolism ◽  
Metabolic Diseases ◽  
New Approaches

Obesity, type 2 diabetes mellitus, metabolic syndrome are metabolic widespread disorders that arise both under the influence of external factors (physical inactivity, high-calorie diet) and under the influence of internal factors. The latter includes the intestinal microbiota which deserves more and more attention in developing new strategies for the correction of metabolic diseases. The discovery of new approaches for the gut microbiota study (metagenomic, metabolomic) gives a new insight into the diversity and involvement of intestinal bacteria in the metabolic processes of the whole organism. This article are reviewed the mechanisms of the gut bacteria impact on lipid and carbohydrate metabolism, the relationship of bacteria species and their metabolites with tissue insulin sensitivity, body mass index. Special attention in the regulation of tissue insulin sensitivity is paid to the role of short-chain fatty acids and secondary bile acids, which are metabolites of gut bacteria. Understanding the influence of human microbiota and its metabolites on lipid and carbohydrate metabolism provides the basis for the development of new approaches to the prevention and treatment of socially significant metabolic diseases such as type 2 diabetes mellitus, obesity, metabolic syndrome.

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