scholarly journals Gut microbiota of mice putatively modifies amino acid metabolism in the host brain

2017 ◽  
Vol 117 (6) ◽  
pp. 775-783 ◽  
Author(s):  
Takahiro Kawase ◽  
Mao Nagasawa ◽  
Hiromi Ikeda ◽  
Shinobu Yasuo ◽  
Yasuhiro Koga ◽  
...  

AbstractRecently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age. Similar patterns were observed for the concentrations of l-Asp in striatum, cerebral cortex and hippocampus, and l-arginine (l-Arg), l-Ala and l-valine (l-Val) in striatum. In addition, the concentrations of l-Asp, d-Ala, l-histidine, l-isoleucine (l-Ile), l-leucine (l-Leu), l-phenylalanine and l-Val were significantly higher in plasma of SPF mice when compared with those of GF mice. The concentrations of l-Arg, l-Gln, l-Ile and l-Leu were significantly higher in SPF than in GF mice, but those of d-Asp, d-serine and l-serine were higher in some brain regions of GF mice than in those of SPF mice. In conclusion, the concentration of amino acids in the host brain seems to be dependent on presence of the gut microbiota. Amino acid metabolism in the host brain may be modified by manipulating microbiota communities.

2004 ◽  
Vol 82 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Enoka P Wijekoon ◽  
Craig Skinner ◽  
Margaret E Brosnan ◽  
John T Brosnan

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.


2003 ◽  
Vol 15 (1) ◽  
pp. 38-43 ◽  
Author(s):  
L Pepplinkhuizen ◽  
F M M A van der Heijden ◽  
S Tuinier ◽  
W M A Verhoeven ◽  
D Fekkes

Background:The pathogenesis of atypical psychoses, in particularly those characterized by polymorphic psychopathology, is hypothesized to be related to disturbances in amino acid metabolism.Objective:In the present study, the role of the amino acid serine was investigated in patients with acute transient polymorphic psychosis.Methods:Patients were loaded with serine and with the amino acids glycine and alanine as controls and subsequently evaluated for the development of psychopathological symptoms. In addition, plasma levels of amino acids were measured.Results:In a subgroup of patients suffering from atypical psychoses, this biochemical challenge resulted in the reappearance of psychedelic symptoms in particular. Furthermore, significantly lower plasma concentrations of serine were found. In vitro experiments revealed a disturbance in the one-carbon metabolism. In another group of patients the loading provoked vegetative symptoms and fatigue.Conclusions:Disturbances in amino acid metabolism may be involved in the emergence of certain psychotic disorders.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xueyuan Yang ◽  
Bangjian Dong ◽  
Lijun An ◽  
Qi Zhang ◽  
Yao Chen ◽  
...  

Accumulating evidences suggested an association between gut microbiome dysbiosis and impaired glycemic control. Ginsenoside Rb1 (Rb1) is a biologically active substance of ginseng, which serves anti-diabetic effects. However, its working mechanism especially interaction with gut microbes remains elusive in detail. In this study, we investigated the impact of Rb1 oral supplementation on high fat diet (HFD) induced obesity mice, and explored its mechanism in regulating blood glucose. The results showed that higher liver weight and lower cecum weight were observed in HFD fed mice, which was maintained by Rb1 administration. In addition, Rb1 ameliorated HFD induced blood lipid abnormality and improved insulin sensitivity. Several mRNA expressions in the liver were measured by quantitative real-time PCR, of which UCP2, Nr1H4, and Fiaf were reversed by Rb1 treatment. 16S rRNA sequencing analysis indicated that Rb1 significantly altered gut microbiota composition and increased the abundance of mucin-degrading bacterium Akkermansia spp. compared to HFD mice. As suggested via functional prediction, amino acid metabolism was modulated by Rb1 supplementation. Subsequent serum amino acids investigation indicated that several diabetes associated amino acids, like branched-chain amino acids, tryptophan and alanine, were altered in company with Rb1 supplementation. Moreover, correlation analysis firstly implied that the circulation level of alanine was related to Akkermansia spp.. In summary, Rb1 supplementation improved HFD induced insulin resistance in mice, and was associated with profound changes in microbial composition and amino acid metabolism.


1973 ◽  
Vol 28 (7-8) ◽  
pp. 449-451 ◽  
Author(s):  
G. Peter ◽  
H. Angst ◽  
U. Koch

Free and protein-bound amino acids in serum and scales were investigated. In serum the bound amino acids of psoriatics are significantly higher with exception of Pro, Met, Tyr and Phe in contrast to normal subjects. For free amino acids the differences between normal subjects and psoriatics found in serum and scales are not significant. Results are discussed in relation to the single amino acids and the biochemical correlations are outlined which takes the pathological process as a basis.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.


PEDIATRICS ◽  
1961 ◽  
Vol 27 (4) ◽  
pp. 539-550 ◽  
Author(s):  
William L. Nyhan ◽  
Margaret Borden ◽  
Barton Childs

The amino acids of blood and urine have been investigated using chromatography on cation exchange columns in the study of a patient with idiopathic hyperglycinemia. Marked increases in concentrations of glycine, serine, alanine, isoleucine and valine were found in the plasma. These changes were not reflected in increased excretion of these amino acids in the urine (with the exception of glycine). Restriction of the dietary intake of protein resulted in a decrease in the concentrations of glycine and other amino acids in the blood and urine, and there was a concomitant decrease in the frequency and severity of episodes of acute illness. The oral administration of leucine was found to induce a decrease in the levels of a number of amino acids in the patient and in controls. Continued decrease during the 3 hours of observation was noted for serine, isoleucine and valine. A mild but progressive decrease in threonine concentration was observed in the controls, while in the patient the concentration increased after the administration of leucine. Decreased levels at 1½ hours, returning toward the fasting levels at 3 hours, were observed for alanine, taurine and glycine. These apparently normal responses to leucine loads were not mediated through increase in the urinary excretion of the amino acids involved, and the data are interpreted to indicate entry of these amino acids into cells.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhichang Wang ◽  
Jun Hu ◽  
Wenyong Zheng ◽  
Tao Yang ◽  
Xinkai Wang ◽  
...  

Abstract Background Early-weaning of piglets is often accompanied by severe disorders, especially diarrhea. The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host. Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets. However, the metabolic response to L. frumenti administration remains unclear. Then, we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L. frumenti or phosphate-buffered saline (PBS). Results A total of 100 6-day-old crossbred piglets (Landrace × Yorkshire) were randomly divided into two groups and piglets received PBS (sterile, 2 mL) or L. frumenti (suspension in PBS, 108 CFU/mL, 2 mL) by oral administration once per day from 6 to 20 days of age. Piglets were weaned at 21 days of age. Serum and liver samples for metabolomic analyses were collected at 26 days of age. Principal components analysis (PCA) showed that L. frumenti altered metabolism in serum and liver. Numerous correlations (P < 0.05) were identified among the serum and liver metabolites that were affected by L. frumenti. Concentrations of guanosine monophosphate (GMP), inosine monophosphate (IMP), and uric acid were higher in serum of L. frumenti administration piglets. Pathway analysis indicated that L. frumenti regulated fatty acid and amino acid metabolism in serum and liver. Concentrations of fatty acid β-oxidation related metabolites in serum (such as 3-hydroxybutyrylcarnitine, C4-OH) and liver (such as acetylcarnitine) were increased after L. frumenti administration. Conclusions Our findings suggest that L. frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets, where it promotes fatty acid β-oxidation and energy production. High serum concentrations of nucleotide intermediates, which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets, were further detected. These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.


2019 ◽  
Vol 316 (4) ◽  
pp. E660-E673 ◽  
Author(s):  
Katrine D. Galsgaard ◽  
Marie Winther-Sørensen ◽  
Jens Pedersen ◽  
Sasha A. S. Kjeldsen ◽  
Mette M. Rosenkilde ◽  
...  

Glucagon and insulin are important regulators of blood glucose. The importance of insulin receptor signaling for alpha-cell secretion and of glucagon receptor signaling for beta-cell secretion is widely discussed and of clinical interest. Amino acids are powerful secretagogues for both hormones, and glucagon controls amino acid metabolism through ureagenesis. The role of insulin in amino acid metabolism is less clear. Female C57BL/6JRj mice received an insulin receptor antagonist (IRA) (S961; 30 nmol/kg), a glucagon receptor antagonist (GRA) (25-2648; 100 mg/kg), or both GRA and IRA (GRA + IRA) 3 h before intravenous administration of similar volumes of saline, glucose (0.5 g/kg), or amino acids (1 µmol/g) while anesthetized with isoflurane. IRA caused basal hyperglycemia, hyperinsulinemia, and hyperglucagonemia. Unexpectedly, IRA lowered basal plasma concentrations of amino acids, whereas GRA increased amino acids, lowered glycemia, and increased glucagon but did not influence insulin concentrations. After administration of GRA + IRA, insulin secretion was significantly reduced compared with IRA administration alone. Blood glucose responses to a glucose and amino acid challenge were similar after vehicle and GRA + IRA administration but greater after IRA and lower after GRA. Anesthesia may have influenced the results, which otherwise strongly suggest that both hormones are essential for the maintenance of glucose homeostasis and that the secretion of both is regulated by powerful negative feedback mechanisms. In addition, insulin limits glucagon secretion, while endogenous glucagon stimulates insulin secretion, revealed during lack of insulin autocrine feedback. Finally, glucagon receptor signaling seems to be of greater importance for amino acid metabolism than insulin receptor signaling.


2020 ◽  
Vol 26 (4) ◽  
pp. 277-287
Author(s):  
Christine Leary ◽  
Roger G Sturmey

Abstract The pattern of metabolism by early embryos in vitro has been linked to a range of phenotypes, including viability. However, the extent to which metabolic function of embryos is modified by specific methods used during ART has yet to be fully described. This study has sought to determine if the mode of fertilization used to create embryos affects subsequent embryo metabolism of substrates. A metabolic profile, including consumption of key substrates and the endogenous triglyceride content of individual IVF and ICSI supernumerary embryos, was assessed and compared. Embryo development and quality was also recorded. All embryos were donated at a single clinical IVF center, on Day 5, from 36 patients aged 18–38 years, The data revealed that consumption of glucose and pyruvate, and production of lactate, did not differ between embryos created by IVF or ICSI. Similarly, the mode of insemination did not impact on the triglyceride content of embryos. However, ICSI-derived embryos displayed a more active turnover of amino acids (P = 0.023), compared to IVF embryos. The specific amino acids produced in higher quantities from ICSI compared to IVF embryos were aspartate (P = 0.016), asparagine (P = 0.04), histidine (P = 0.021) and threonine (P = 0.009) while leucine consumption was significantly lower (P = 0.04). However, importantly neither individual nor collective differences in amino acid metabolism were apparent for sibling oocytes subjected to either mode of fertilization. Embryo morphology (the number of top grade embryos) and development (proportion reaching the blastocyst stage) were comparable in patients undergoing IVF and ICSI. In conclusion, the microinjection of spermatozoa into oocytes does not appear to have an impact on subsequent metabolism and viability. Observed differences in amino acid metabolism may be attributed to male factor infertility of the patients rather than the ICSI procedure per se.


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