The Pharmabiotic Approach to Treat Hyperammonemia

Liu, Jing; Lkhagva, Enkhchimeg; Chung, Hea-Jong; Kim, Hyeon Jin; Hong, Seong‐Tshool

doi:10.3390/nu10020140

Cited by 82 publications

(107 citation statements)

References 120 publications

(130 reference statements)

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“…The human gut microbiome has been shown to differ in almost every different cohort. Also, the human gut microbiome affects our traits as much as our own genome does [1][2][3][4][5][6]16]. Realization of such signi cant role of gut microbiome rose to the concept of human as a superorganism that is the conglomerate of human and microbial cells.…”

Section: Discussionmentioning

confidence: 99%

“…Gut microbiome is not also essential to the health and well-being of the host but also even determines the human traits as much as our own genes [2]. Especially, the role of gut microbiome was notable in the case of atherosclerosis, hypertension, obesity, diabetes, metabolic syndrome, in ammatory bowel disease (IBD), gastrointestinal tract malignancies, hepatic encephalopathy, allergies, behavior, intelligence, autism, neurological diseases, and psychological diseases [1][2][3][4][5][6]. Thus, the composition of gut microbiome and its role on human health and disease became a booming area of research, presenting a new paradigm of opportunities for medical and food applications [1].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the stability and dynamics of the gut microbiome will have not only local but also systemic effects which may determine the health and well-being of the host [8]. Gut microbiome develops rapidly right after birth and uctuates for ~2 years until it matures [2][3][4][5][6]. It has been generally believed that the composition of gut microbiome remains stably maintained throughout life once a certain type of gut microbiome is established on an individual basis [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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The Physiological Condition of Host Affects more Significantly Gut Microbiome than Diet

Chung¹,

Lkhagva²,

Hong³

2020

Preprint

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Background: The gut microbiome, which is composed of trillions of microbes, plays a fundamental role in human health and disease. Each individual has a unique profile of gut microbiome which plays specific functions in its host. Although multiple factors might affect the diversity of gut microbiome, physiological condition and diet are considered as main determining factors for gut microbiome diversity.Results: We performed a comparative study to elucidate which one between physiological condition and diet affects more significantly gut microbiome diversity by comparing the effect of a vegetarian diet and a light physical exercise. Although both Physical exercise and vegetarian diet affected significantly the composition of gut microbiome, the patterns of affection were different. The physical exercise increased the populations of Firmicutes and Actinobacteria, whereas the vegetarian diet increased the populations of Bacteroidetes and Actinobacteria. Flourishing of Megamonas funiformis was most notable by the physical exercise while flourishing Prevotella and decreasing Bacteroides was most notable by the vegetarian diet. Maximum-likelihood phylogenetic tree analysis comprising all of the taxa, the taxonomic α-diversity measurement by ACE richness, Shannon and Simpson, and HCL heatmap analysis at Genus level showed that the physical exercise affected the microbial community more significantly than diet shift, and the diversities of gut microbiome were slightly decreased in both cases. Both NMDS heatmap and Fast UniFrac analysis further confirmed that physical exercise affected the composition of gut microbiome more significantly than vegetarian diet. The NMDS plots based on Bray-Curtis distances validated that the original composition of gut microbiome became diverged into a different direction by either physical exercise or vegetarian diet. Conclusion: The physiological condition of host contributes more significantly to the composition of gut microbiome than diet, which means that the composition of gut microbiome is more significantly affected by a host factor than diet. This work also would provide a new theoretical basis why physical exercises is more health-beneficial than vegetarian diets.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Physiological Condition of Host Affects more Significantly Gut Microbiome than Diet

Chung¹,

Lkhagva²,

Hong³

2020

Preprint

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“…Long-term low-degree hyperammonemia may be associated with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, etc. [71]. This condition can be caused by both hereditary deficiencies in the enzymes of the uric acid cycle, for example, arginase, and chronic or acute liver diseases.…”

Section: Ammocytesmentioning

confidence: 99%

Erythrocytes as Carriers: From Drug Delivery to Biosensors

et al. 2020

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Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug's action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.Pharmaceutics 2020, 12, 276 2 of 44 property of RBCs allows to load them with biologically active substances of different molecular weights. For these reasons, erythrocytes are promising biocompatible cells for drug delivery.The methods for incorporating various substances into red blood cells differ in the way that substances penetrate the cells. The cause of permeability may be the pores' formation in the cell membrane due to a physical exposure (high voltage electric pulse [10,11] or ultrasound [12]). Drug molecules can also enter the RBCs by endocytosis in the presence of certain chemical compounds (for example, primaquine [13], vinblastine, chlorpromazine, hydrocortisone or tetracaine [14,15]), or using the cell-penetrating peptides bounded to the compound that should be encapsulated [16]. However, the most popular are different variants of osmotic methods.In some cases, RBCs are first exposed to a hyperosmotic pulse of a low molecular weight substance that penetrates very well through the cell membrane (for example, dimethyl sulfoxide (DMSO) [17,18] or glucose [19,20]). After washing the cells, which decreases the external concentration of these compounds and creates a gradient of their concentration between both sides of the RBC membrane, the target drug is introduced into the external volume. Water with this drug begins to enter into the cells to decrease the osmotic pressure there. The process ends when the gradient of DMSO or glucose disappears. The pores close and part of the drug remains into RBCs. Other, the most popular of the osmotic methods are hypoosmotic. These methods are based on creating a hypotonic environment around RBCs, which causes swelling of the cells and opening pores in the cellular membrane, through which therapeutic compounds can penetrate RBCs. Then, a hypertonic solution is introduced into the cell suspension. The pores close, the cells restore their original size, trapping the drug molecules inside the cell. Osmotic methods are divided into severa...

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“…Mann-Whitney U test, p<0.05) than those in the male group. In the gut, ammonia produced by ureolytic bacteria is absorbed into the bloodstream and used to fuel hepatic ureagenesis [25].…”

Section: Hypogonadal Male Animals Exhibit a High Intestinal Microbialmentioning

confidence: 99%

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

Whon

Kim

Shin

et al. 2019

Preprint

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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.

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The Pharmabiotic Approach to Treat Hyperammonemia

Cited by 82 publications

References 120 publications

The Physiological Condition of Host Affects more Significantly Gut Microbiome than Diet

The Physiological Condition of Host Affects more Significantly Gut Microbiome than Diet

Erythrocytes as Carriers: From Drug Delivery to Biosensors

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

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