scholarly journals Interrogation of the Perturbed Gut Microbiota in Gouty Arthritis Patients Through in silico Metabolic Modeling

Author(s):  
Michael A. Henson

Recent studies have shown perturbed gut microbiota associated with gouty arthritis, a metabolic disease in which an imbalance between uric acid production and excretion leads to the deposition of uric acid crystals in joints. To mechanistically investigate altered microbiota metabolism in gout disease, 16S rRNA gene amplicon sequence data from stool samples of gout patients and healthy controls were computationally analyzed through bacterial community metabolic modeling. Patient-specific models were used to cluster samples according to their metabolic capabilities and to generate statistically significant partitioning of the samples into a Bacteroides-dominated, high gout cluster and a Faecalibacterium-elevated, low gout cluster. The high gout cluster samples were predicted to allow elevated synthesis of the amino acids D-alanine and L-alanine and byproducts of branched-chain amino acid catabolism, while the low gout cluster samples allowed higher production of butyrate, the sulfur-containing amino acids L-cysteine and L-methionine and the L-cysteine catabolic product H2S. The models predicted an important role for metabolite crossfeeding, including the exchange of acetate, D-lactate and succinate from Bacteroides to Faecalibacterium to allow higher butyrate production differences than would be expected based on taxa abundances in the two clusters. The surprising result that the high gout cluster could underproduce H2S despite having a higher abundance of H2S-synthesizing bacteria was rationalized by reduced L-cysteine production from Faecalibacterium in this cluster. Model predictions were not substantially altered by constraining uptake rates with different in silico diets, suggesting that sulfur-containing amino acid metabolism generally and H2S more specifically could be novel gout disease markers.

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S42-S42
Author(s):  
Kohei Sugihara ◽  
Nobuhiko Kamada

Abstract Background Recent accumulating evidence suggests that amino acids have crucial roles in the maintenance of intestinal homeostasis. In inflammatory bowel disease (IBD), amino acid metabolism is changed in both host and the gut microbiota. Among amino acids, L-serine plays a central role in several metabolic processes that are essential for the growth and survival of both mammalian and bacterial cells. However, the role of L-serine in intestinal homeostasis and IBD remains incompletely understood. In this study, we investigated the effect of dietary L-serine on intestinal inflammation in a murine model of colitis. Methods Specific pathogen-free (SPF) mice were fed either a control diet (amino acid-based diet) or an L-serine-deficient diet (SDD). Colitis was induced by the treatment of dextran sodium sulfate (DSS). The gut microbiome was analyzed by 16S rRNA sequencing. We also evaluate the effect of dietary L-serine in germ-free mice and gnotobiotic mice that were colonized by a consortium of non-mucolytic bacterial strains or the consortium plus mucolytic bacterial strains. Results We found that the SDD exacerbated experimental colitis in SPF mice. However, the severity of colitis in SDD-fed mice was comparable to control diet-fed mice in germ-free condition, suggesting that the gut microbiota is required for exacerbation of colitis caused by the restriction of dietary L-serine. The gut microbiome analysis revealed that dietary L-serine restriction fosters the blooms of a mucus-degrading bacterium Akkermansia muciniphila and adherent-invasive Escherichia coli in the inflamed gut. Consistent with the expansion of mucolytic bacteria, SDD-fed mice showed a loss of the intestinal mucus layer. Dysfunction of the mucus barrier resulted in increased intestinal permeability, thereby leading to bacterial translocation to the intestinal mucosa, which subsequently increased the severity of colitis. The increased intestinal permeability and subsequent bacterial translocation were observed in SDD-fed gnotobiotic mice that colonized by mucolytic bacteria. In contrast, dietary L-serine restriction did not alter intestinal barrier integrity in gnotobiotic mice that colonized only by non-mucolytic bacteria. Conclusion Our results suggest that dietary L-serine regulates the integrity of the intestinal mucus barrier during inflammation by limiting the expansion of mucus degrading bacteria.


2016 ◽  
Vol 11 (5) ◽  
pp. 683-694 ◽  
Author(s):  
Farouq S. Mjalli ◽  
Rashid Al-Hajri ◽  
Ala'a Al-Muhtaseb ◽  
Omar Ahmed ◽  
Maddela Nagaraju

1978 ◽  
Vol 33 (3-4) ◽  
pp. 203-209 ◽  
Author(s):  
Vera Jakubick ◽  
Henry Delincée

When myoglobin is irradiated in the presence of amino acids, the most radiation-reactive species, like the aromatic and sulfur-containing amino acids, will bind preferentially to the protein. The radiation-induced binding is strongly dependent on the concentration of protein and amino acid. Subsequent to irradiation of myoglobin in the presence of radioactively labelled tryptophan followed by tryptic hydrolysis, only a single radioactive spot was detected on the fingerprint. The binding of amino acids is thus not randomly distributed over the protein molecule but occurs at specific reactive sites.


1969 ◽  
Vol 47 (5) ◽  
pp. 679-685 ◽  
Author(s):  
A. J. Finlayson ◽  
R. S. Bhatty ◽  
C. M. Christ

Two proteins, previously described by the authors as BI (S020, buffer 12 S) and AIVS (S020, w 1.7 S) have been isolated from eight varieties of rapeseed belonging to Brassica campestris L. and Brassica napus L. species. These proteins have similar chromatographic and electrophoretic characteristics but differ in amino acid composition, particularly with regard to the sulfur-containing amino acids. One of the rapeseed samples was obtained from plants grown on sulfur-deficient soil. The sulfur deficiency produced, in the mature seed, a much reduced protein content and appeared to affect the structure of the protein BI.


2021 ◽  
Vol 4 (1) ◽  
pp. 56-72
Author(s):  
Mykhailo Peresichnyi ◽  
Svitlana Peresichna ◽  
Anna Sobko

The topicality. To date, the structure of the population’s diet has significant deviations from the formula of a balanced diet in terms of protein intake, including sulfur-containing, which causes the formation of risk factors for the development alimentary and alimentary-dependent diseases. For the prevention of diseases caused by protein deficiency, it is promising to increase its content in vegetable dishes due to the integrated use of raw materials and dietary supplements of high biological value. It is advisable to use food combinatorics in the innovative technologies development for vegetable dishes of improved amino acid composition. The purpose of the study is food combinatorics of amino acid composition of potato croquettes with soy flour, wheat germ; natural shrimp powder “Rieber Food Ingredients” and lentil-spirulina filling in terms of content and balance of essential and substitute amino acids and the degree of their assimilation by the human body. Research methods. Physicochemical, mathematical and statistical methods of experimental data processing with the use of information technologies, methods of ion exchange liquid column chromatography and qualimetric methods have been used. Results. Research is aimed at the use of food combinatorics and scientific substantiation of the amino acid composition of potato croquettes with the use of protein vegetable and non-fish water raw materials and dietary supplements. As a result of scientific researches the food combinatorics at development of technology of vegetable dishes has been carried out, the amino acid structure has been proved and experimentally generalized, the amino acid score and balance of sulfur-containing amino acids in the complex use of potato mass with wheat germ, soy flour, natural shrimp powder “Rieber Food Ingredients” and lentil-spirulina filling in culinary products have been analyzed. The social effect of fuller use of vegetable, non-fish water raw materials, expansion of the range of vegetable dishes with improved amino acid composition and consumer properties of potato dishes in restaurants, preservation and protection of public health has been confirmed. Conclusions and discussions. Food combinatorics was carried out during the potato croquet technology development with the use of protein vegetable and non-fish water raw materials, which contributed to the improvement of the amino acid composition of vegetable dishes and, in particular, to the increase of their biological value.


2019 ◽  
Author(s):  
Tae Woong Whon ◽  
Hyun Sik Kim ◽  
Na-Ri Shin ◽  
Eun Sung Jung ◽  
Euon Jung Tak ◽  
...  

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.


2018 ◽  
Vol 5 (10) ◽  
pp. 289-301
Author(s):  
Ruma Ganguly ◽  
Sailesh K. Mehta

The role of amino acid is important to Jasmonate induce plant defense process. Jasmonic acid and amino acid Isoleucine conjugate (JA-Ile) has been found to be necessary to achieve such process effectively. We have examined the origin of such process computationally and showed that Isoleucine is more active compared to other Jasmonic acid conjugates. The epimerization process revealed that Isoleucine conjugated Jasmonic acid is energetically a favoured process compared to JA-Leu and JA-Val. Water has functioned as a catalyst in the whole epimerization process. This study would unravel the importance of Isoleucine in the Jasmonic acid induced plant defense process.


Proceedings ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Petar Stanić ◽  
Marija Živković ◽  
Biljana Šmit

Hydantoins and their sulfur containing analogues, thiohydantoins, are cyclic ureides that have attracted huge attention ever since their discovery. Most of them are biologically active compounds and several points of structural diversity have made them very synthetically attractive. Although substituents can be introduced to the hydantoin nucleus, most substituted hydantoins are synthesized from substrates already containing these groups, while forming the hydantoin nucleus. This is a common route to the synthesis of hydantoins and one of them is employed in this study. A series of 3-allyl-2-thiohydantoins is synthesized from various α-amino acids in a reaction with allyl isothiocyanate. The substitution of the acquired thiohydantoin depends on the structure of the starting α-amino acid. The residual group of the α-amino acid becomes the substituent at the C5-position, while N-monosubstituted amino acids give rise to a substituent in the N1-position. The reaction is carried out in a two-step process and the reaction conditions generally depend on the nature of the amino acid itself. All thiohydantoins are obtained in a good yield and fully characterized by NMR and IR spectroscopy, as well as X-ray crystallography.


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