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 Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome

2021 ◽  
Vol 11 ◽  
Author(s):  
Lin Xiao ◽  
Qin Liu ◽  
Mei Luo ◽  
Lishou Xiong
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Functional Bowel Disorder ◽  
Irritable Bowel ◽  
The Brain ◽  
Bowel Disorder

Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiology remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiological factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, especially bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.

scholarly journals Antibiotic Exposure Has Sex-Dependent Effects on the Gut Microbiota and Metabolism of Short-Chain Fatty Acids and Amino Acids in Mice

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Hongchang Gao ◽  
Qi Shu ◽  
Jiuxia Chen ◽  
Kai Fan ◽  
Pengtao Xu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Antibiotic Exposure ◽  
Male Mice ◽  
Female Mice ◽  
Structural Composition ◽  
Host Metabolism

ABSTRACT The gut microbiota has the capability to regulate homeostasis of the host metabolism. Since antibiotic exposure can adversely affect the microbiome, we hypothesized that antibiotic effects on the gut microbiota and host metabolism are sex dependent. In this study, we examined the effects of antibiotic treatments, including vancomycin (Vanc) and ciprofloxacin-metronidazole (CiMe), on the gut microbiome and metabolome in colonic contents and tissues in both male and female mice. We found that the relative abundances and structural composition of Firmicutes were significantly reduced in female mice after both Vanc and CiMe treatments but in male mice only after treatment with Vanc. However, Vanc exposure considerably altered the relative abundances and structural composition of representatives of the Proteobacteria especially in male mice. The levels of short-chain fatty acids (SCFAs; acetate, butyrate, and propionate) in colonic contents and tissues were significantly decreased in female mice after both antibiotic treatments, while these reductions were detected in male mice only after Vanc treatment. However, another SCFA, formate, exhibited the opposite tendency in colonic tissues. Both antibiotic exposures significantly decreased the levels of alanine, branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) and aromatic amino acids (AAAs; phenylalanine and tyrosine) in colonic contents of female mice but not in male mice. Additionally, female mice had much greater correlations between microbe and metabolite than male mice. These findings suggest that sex-dependent effects should be considered for antibiotic-induced modifications of the gut microbiota and host metabolism. IMPORTANCE Accumulating evidence shows that the gut microbiota regulates host metabolism by producing a series of metabolites, such as amino acids, bile acids, fatty acids, and others. These metabolites have a positive or negative effect on host health. Antibiotic exposure can disrupt the gut microbiota and thereby affect host metabolism and physiology. However, there are a limited number of studies addressing whether antibiotic effects on the gut microbiota and host metabolism are sex dependent. In this study, we uncovered a sex-dependent difference in antibiotic effects on the gut microbiota and metabolome in colonic contents and tissues in mice. These findings reveal that sex-dependent effects need to be considered for antibiotic use in scientific research or clinical practice. Moreover, this study will also give an important direction for future use of antibiotics to modify the gut microbiome and host metabolism in a sex-specific manner.

scholarly journals Microbiota and Diabetes Mellitus: Role of Lipid Mediators

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3039
Author(s):  
Juan Salazar ◽  
Lissé Angarita ◽  
Valery Morillo ◽  
Carla Navarro ◽  
María Sofía Martínez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Fatty Acids ◽  
Immune System ◽  
Gut Microbiota ◽  
Eating Habits ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Lipid Mediators

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.

scholarly journals Genetic Support for a Causal Role of Insulin Resistance on Circulating Branched-Chain Amino Acids and Inflammation

Diabetes Care ◽  
2017 ◽  
Vol 40 (12) ◽  
pp. 1779-1786 ◽  
Author(s):  
Qin Wang ◽  
Michael V. Holmes ◽  
George Davey Smith ◽  
Mika Ala-Korpela
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Causal Role ◽  
Branched Chain

scholarly journals Berberine alleviates insulin resistance by reducing peripheral branched-chain amino acids

2019 ◽  
Vol 316 (1) ◽  
pp. E73-E85 ◽  
Author(s):  
Shi-Jun Yue ◽  
Juan Liu ◽  
Ai-Ting Wang ◽  
Xin-Tong Meng ◽  
Zhi-Rui Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Gut Microbiota ◽  
Ex Vivo ◽  
Elevated Serum ◽  
Branched Chain Amino Acids ◽  
Chow Diet ◽  
Adipose Tissues ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Increased circulating branched-chain amino acids (BCAAs) have been involved in the pathogenesis of obesity and insulin resistance (IR). However, evidence relating berberine (BBR), gut microbiota, BCAAs, and IR is limited. Here, we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet (HFD)-fed mice. BBR reorganized gut microbiota populations under both the normal chow diet (NCD) and HFD. Particularly, BBR noticeably decreased the relative abundance of BCAA-producing bacteria, including order Clostridiales; families Streptococcaceae, Clostridiaceae, and Prevotellaceae; and genera Streptococcus and Prevotella. Compared with the HFD group, predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment. Accordingly, the elevated serum BCAAs of HFD group were significantly decreased by BBR. Furthermore, the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by activation of the multienzyme branched-chain α-ketoacid dehydrogenase complex (BCKDC), whereas by inhibition of the phosphorylation state of BCKDHA (E1α subunit) and branched-chain α-ketoacid dehydrogenase kinase (BCKDK). The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes. Finally, data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs. Together, our findings clarified BBR improving IR associated not only with gut microbiota alteration in BCAA biosynthesis but also with BCAA catabolism in liver and adipose tissues.

scholarly journals A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids

Metabolomics ◽  
2013 ◽  
Vol 9 (4) ◽  
pp. 818-827 ◽  
Author(s):  
Xiaojiao Zheng ◽  
Yunping Qiu ◽  
Wei Zhong ◽  
Sarah Baxter ◽  
Mingming Su ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Branched Chain Amino Acids ◽  
Short Chain ◽  
Branched Chain ◽  
Chain Fatty Acids

scholarly journals The relationship between BMI and metabolomic profiles: a focus on amino acids

2012 ◽  
Vol 71 (4) ◽  
pp. 634-638 ◽  
Author(s):  
Ciara Morris ◽  
Colm O'Grada ◽  
Miriam Ryan ◽  
Helen M. Roche ◽  
Michael J. Gibney ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Weight Gain ◽  
Metabolic Profile ◽  
Metabolic Regulation ◽  
Branched Chain Amino Acids ◽  
Branched Chain ◽  
The Relationship ◽  
Targeted Approach

The role of metabolomics in the field of nutrition is continuing to grow and it has the potential to assist in the understanding of metabolic regulation and explain how minor perturbations can have a multitude of biochemical endpoints. It is this development, which creates the potential to provide the knowledge necessary to facilitate a more targeted approach to nutrition. In recent years, there has been interest in applying metabolomics to examine alterations in the metabolic profile according to weight gain/obesity. Emerging from these studies is the strong evidence that alterations in the amino acid (AA) profiles are associated with obesity. Several other studies have also shown a relationship between branched-chain amino acids (BCAA), obesity and insulin resistance. The present review focuses on the proposed link between AA and in particular BCAA, obesity and insulin resistance. In conclusion, a wealth of information is accumulating to support the role of AA, and in particular of the BCAA, in obesity.

BIOSYNTHESIS OF BRANCHED-CHAIN FATTY ACIDS: IV. FACTORS AFFECTING RELATIVE ABUNDANCE OF FATTY ACIDS PRODUCED BY BACILLUS SUBTILIS

1966 ◽  
Vol 12 (3) ◽  
pp. 501-514 ◽  
Author(s):  
Toshi Kaneda
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Bacillus Subtilis ◽  
Relative Abundance ◽  
Short Chain Fatty Acids ◽  
Branched Chain Amino Acids ◽  
Factors Affecting ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Chain Fatty Acids

The fatty acids produced by Bacillus subtilis may be grouped into four pairs: 12-methyltetradecanoic and 14-methylhexadecanoic acids (anteiso-C15and anteiso-C17), 13-methyltetradecanoic and 15-methylhexadecanoic acids (iso-C15and iso-C17), 12-methyltridecanoic and 14-methylpentadecanoic acids (iso-C14and iso-C16), and myristic and palmitic acids (n-C14and n-C16). Any one of the branched-chain amino acids, L-isoleucine, L-leucine, or L-valine, or of the branched short-chain fatty acids, α-methylbutyrate, isovalerate, or isobutyrate, added to the glucose – yeast extract medium increased the synthesis of the specific pairs of fatty acids structurally related to the added substrate and decreased the synthesis of other fatty acids. This indicates that the relative abundance of branched-chain fatty acids in B. subtilis is a function of the relative availability of the precursors of the terminal portions of the fatty acids, presumably α-methylbutyryl-CoA, isovaleryl-CoA, and isobutyryl-CoA. This mechanism is consistent with the relative abundances of branched-chain fatty acids found in mutants of B. subtilis which require particular branched-chain amino acids. The biotin content of the culture medium and the length of incubation time also affected the relative abundance of the fatty acids.

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