ArticlePublisher preview availableLiterature Review

A review of the relationship between the gut microbiota and amino acid metabolism

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

New evidence has emerged in recent years to suggest a strong link between the human gut microbiota, its metabolites, and various physiological aspects of hosts along with important pathophysiological dimensions of diseases. The research indicates that the gut microbiota can facilitate metabolite production in two ways: first, the resident species of the gut microbiota use the amino acids produced from food or the host as elements for protein synthesis, and second, conversion or fermentation are used to drive nutrient metabolism. Additionally, the gut microbiota can synthesize several nutritionally essential amino acids de novo, which is a potential regulatory factor in amino acid homeostasis. The primary objective of this review is to summarize the current literature relating to the ways in which microbial amino acids contribute to host amino acid homeostasis.
This content is subject to copyright. Terms and conditions apply.
Vol.:(0123456789)
1 3
Amino Acids (2017) 49:2083–2090
DOI 10.1007/s00726-017-2493-3
REVIEW ARTICLE
A review oftherelationship betweenthegut microbiota
andamino acid metabolism
RuiLin1 · WentianLiu1· MeiyuPiao1· HongZhu2
Received: 4 July 2017 / Accepted: 11 September 2017 / Published online: 20 September 2017
© Springer-Verlag GmbH Austria 2017
qualitative transformations associated with several metabo-
lites generated by the gut microbiota are implicated in the
pathophysiological dimensions of illnesses such as meta-
bolic syndrome, inflammatory bowel disease, diabetes mel-
litus (types 1 and 2), asthma, colon cancer, obesity, major
depression, and autism (Diaz Heijtz etal. 2011; Vijay-Kumar
etal. 2010; Uronis etal. 2009; De Filippo etal. 2010).
A fundamental function of the gut microbiota that has
long been understood by the research community is the
metabolism of indigestible matter consumed by the host,
thereby contributing to optimal energy production. In this
context, as a prominent part of the human diet, amino acids
play a crucial role not simply by serving as the basic ele-
ments of proteins and peptides, but more importantly in driv-
ing the production of numerous bioactive molecules that
contribute to the maintenance of signaling pathways and
metabolism (Sato etal. 2006; Wu 2013; Wu etal. 2014).
Researchers have compared germ-free mice and convention-
alized mice and found that the latter possessed an altered
distribution of free amino acids in the gastrointestinal (GI)
tract, importantly indicating that the resident species of the
gut microbiota are crucial to host amino acid homeostasis
and health (Mardinoglu etal. 2015). The purpose of the
present review is to outline how host nutritional status and
physiological health are prominently influenced by amino
acid metabolism in the gut microbiota.
Microbial amino acid metabolism
Gut microbiota andtheregulation ofamino acid
catabolism andutilization
The gut microbiota performs a crucial function in facilitat-
ing the regulation of the amino acid pool and profile over
Abstract New evidence has emerged in recent years to
suggest a strong link between the human gut microbiota, its
metabolites, and various physiological aspects of hosts along
with important pathophysiological dimensions of diseases.
The research indicates that the gut microbiota can facilitate
metabolite production in two ways: first, the resident spe-
cies of the gut microbiota use the amino acids produced
from food or the host as elements for protein synthesis, and
second, conversion or fermentation are used to drive nutrient
metabolism. Additionally, the gut microbiota can synthesize
several nutritionally essential amino acids de novo, which is
a potential regulatory factor in amino acid homeostasis. The
primary objective of this review is to summarize the cur-
rent literature relating to the ways in which microbial amino
acids contribute to host amino acid homeostasis.
Keywords Amino acids· Gut microbiota· Dietary·
Tryptophan· Obesity· Type 2 diabetes mellitus
Introduction
Host homeostasis with respect to issues of physiology and
metabolism is crucially underpinned by the gut microbiota
and its metabolites (Human Microbiome Project C 2012).
Recent literature indicates that various quantitative and
Handling Editors: C.-A. A. Hu, Y. Yin, Y. Hou, G. Wu, Y. Teng.
* Rui Lin
pubmed1128@126.com
1 Department ofGastroenterology andHepatology, Tianjin
Medical University, General Hospital, Tianjin300052, China
2 Department ofColorectal Surgery, Nankai University
Affiliated Hospital, Tianjin801225, China
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Therefore, the decreased fecal levels of alanine, threonine, aspartate, lysine and glycine could reflect the improved inflammatory status in vivo. In addition, threonine and lysine in the intestine can synthesize butyrate, thus improving the lipid and blood pressure levels (51). ...
Article
Full-text available
The phenomenon of longevity in Guangxi of China proved to be closely relevant to its specific dietary habits, but the exact effects of this diet on health remain to be explored. In this work, fourteen screened volunteers with cardiovascular disease (CVD) risk followed a novel dietary pattern derived from centenarians of Guangxi, China for 2 weeks, then the effects of diet on human health were explored by measuring the health metrics and fecal metabolites. The results showed that the short-term dietary intervention significantly decreased the body weight, body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), mean systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels, while it significantly increased high-density lipoprotein cholesterol (HDL-c) levels. Orthogonal partial least squares discriminant analysis (OPLS-DA) indicated a distinct separation in the fecal metabolic profiles of volunteers before and after the intervention. Nine of these metabolites showed significant differences, including two metabolites increased (butyrate and citrulline), seven metabolites decreased (threonine, choline, glycine, aspartate, alanine, N-acetylglutamic acid and lysine). Pathway and enrichment analysis showed that the reduction in CVD risk by dietary intervention mainly affected five pathways, which include arginine biosynthesis; aminoacyl-tRNA biosynthesis; glycine, serine and threonine metabolism; alanine, aspartate and glutamate metabolism; and valine, leucine and isoleucine biosynthesis. Herein, the Guangxi longevity dietary pattern can provide a feasible healthy diet strategy for reducing the CVD risk and human beings. Clinical trial registration: [http://www.chictr.org.cn], identifier [ChiCTR220 0058216].
... Our results tentatively indicated that alteration of GM might raise thromboembolic risk via alteration of SCFAs metabolism, but further confirmation are needed. Additionally, recent studies suggested a strong link between microbial production of free amino acids and diseases, and that GM participate in de novo synthesis of several nutritionally essential amino acids, which regulate amino acid homeostasis in the host [31][32][33]. Wang et al. found that the concentration of serine produced by gut bacteria was decreased in Alzheimer's disease patients [32]. ...
Article
Full-text available
Background: In our previous studies, we found a disordered taxonomic composition and function of gut microbiota (GM) in atrial fibrillation (AF) patients. However, direct evidence about the association between dysbiotic microbiota and thromboembolic risk in AF is lacking. Aims: In this study, we analyzed the interaction of GM and related functional patterns in AF with different CHA2DS2-VASc scores to assess its potential as a biomarker for predicting stroke risk. Patients and Methods. The CHA2DS2-VASc score was used for thromboembolic risk stratification in AF according to American Heart Association (AHA) guidelines. We investigated the taxonomic and functional annotation of GM based on metagenomic data from 50 AF patients (32 with high thromboembolic risk (CHA2DS2-VASc score ≥2 (males) or CHA2DS2-VASc score ≥3 (females)) and 18 individuals with low thromboembolic risk (CHA2DS2-VASc score <2 (males) or CHA2DS2-VASc score <3 (females))). Results: The gut microbial diversity, composition, and function in AF were different in high and low CHA2DS2-VASc score groups. In high thromboembolic risk group, the abundance of Prevotella, Lachnospiraceae, and Eubacterium rectale, related to the production of short-chain fatty acids and anti-inflammatory were reduced (all P < 0.05). Furthermore, annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG), a database of genes and genomes, the KEGG orthology-based scoring approach exhibited a significant association with thromboembolic risk in AF patients. Conclusions: Imbalance of GM and microbial dysfunction are involved in aggravated thromboembolic risk of AF.
... Metabolites were the functional output of the host and microbiome interactions [50]. Thus, it is no surprise to observe that two different aquaculture models had a great impact on the microbiome-host metabolism and host fitness, the impact possibly involved in energy homeostasis, lipid metabolism, endocrine system, anti-inflammatory activity, and so on (Table S11) [58][59][60][61][62]. In fact, it was observed that the contents of lipid droplets (LDs) were significantly increased in the liver of P. sinensis in the RFC ( Figure 7B,C), which indicated that different aquaculture systems affect the lipid metabolism and energy homeostasis of P. sinensis. ...
Article
Full-text available
The commercial aquatic animal microbiome may markedly affect the successful host's farming in various aquaculture systems. However, very little was known about it. Here, two different aquaculture systems, the rice–fish culture (RFC) and intensive pond culture (IPC) systems, were compared to deconstruct the skin, oral, and gut microbiome, as well as the gut metabolome of juvenile Chinese softshell turtle (Pelodiscus sinensis). Higher alpha‐diversity and functional redundancy of P. sinensis microbial community were found in the RFC than those of the IPC. The aquaculture systems have the strongest influence on the gut microbiome, followed by the skin microbiome, and finally the oral microbiome. Source‐tracking analysis showed that the RFC's microbial community originated from more unknown sources than that of the IPC across all body regions. Strikingly, the RFC's oral and skin microbiome exhibited a significantly higher proportion of generalists and broader habitat niche breadth than those of the IPC, but not the gut. Null model analysis revealed that the RFC's oral and skin microbial community assembly was governed by a significantly greater proportion of deterministic processes than that of the IPC, but not the gut. We further identified the key gene and microbial contribution to five significantly changed gut metabolites, 2‐oxoglutarate, N‐acetyl‐d‐mannosamine, cis‐4‐hydroxy‐d‐proline, nicotinamide, and l‐alanine, which were significantly correlated with important categories of microbe‐mediated processes, including the amino acid metabolism, GABAergic synapse, ABC transporters, biosynthesis of unsaturated fatty acids, as well as citrate cycle. Moreover, different aquaculture systems have a significant impact on the hepatic lipid metabolism and body shape of P. sinensis. Our results provide new insight into the influence of aquaculture systems on the microbial community structure feature and assembly mechanism in an aquatic animal, also highlighting the key microbiome and gene contributions to the metabolite variation in the gut microbiome‐metabolome association. In brief, different aquaculture system induces distinct tissue‐specific microbiome assembly that alters host fitness in part through gut metabolites. Different aquaculture system induces distinct phenotype, microbiome assembly, and gut metabolome. In brief, different aquaculture system induces distinct tissue‐specific microbiome assembly that alters host fitness in part through gut metabolites. Distinct microbial diversity and community structure are driven through different sources and community assembly processes. To identify several key genes and microbial species that contribute to five significantly changed gut metabolites. Different aquaculture system induces distinct phenotype, microbiome assembly, and gut metabolome. In brief, different aquaculture system induces distinct tissue‐specific microbiome assembly that alters host fitness in part through gut metabolites. Distinct microbial diversity and community structure are driven through different sources and community assembly processes. To identify several key genes and microbial species that contribute to five significantly changed gut metabolites.
Article
Gut microbiota is a complex system that starts to take shape early in life. Several factors influence the rise of microbial gut colonization, such as term and mode of delivery, exposure to antibiotics, maternal diet, presence of siblings and family members, pets, genetics, local environment, and geographical location. Breastfeeding, complementary feeding, and later dietary patterns during infancy and toddlerhood are major players in the proper development of microbial communities. Nonetheless, if dysbiosis occurs, gut microbiota may remain impaired throughout life, leading to deleterious consequences, such as greater predisposition to non-communicable diseases, more susceptible immune system and altered gut–brain axis. Children with specific diseases (i.e., food allergies, inborn errors of metabolism, celiac disease) need a special formula and later a special diet, excluding certain foods or nutrients. We searched on PubMed/Medline, Scopus and Embase for relevant pediatric studies published over the last twenty years on gut microbiota dietary patterns and excluded case reports or series and letters. The aim of this review is to highlight the changes in the gut microbiota in infants and children fed with special formula or diets for therapeutic requirements and, its potential health implications, with respect to gut microbiota under standard diets.
Article
The gut microbiome is undoubtedly a key modulator of human health, which can promote or impair homeostasis throughout life. This is even more relevant in old age, when there is a gradual loss of function in multiple organ systems, related to growth, metabolism, and immunity. Several studies have described changes in the gut microbiome across age groups up to the extreme limits of lifespan, including maladaptations that occur in the context of age-related conditions, such as frailty, neurodegenerative diseases, and cardiometabolic diseases. The gut microbiome can also interact bi-directionally with anti-age-related disease therapies, being affected and in turn influencing their efficacy. In this framework, the development of integrated microbiome-based intervention strategies, aimed at favoring a eubiotic configuration and trajectory, could therefore represent an innovative approach for the promotion of healthy aging and the achievement of longevity.
Article
Full-text available
El síndrome metabólico (SMet) es un problema complejo de salud pública mundial, enfermedades relacionadas con él son causa de muerte que en el año 2020 fue del 43%. El tratamiento y la prevención del SMet sin el uso de fármacos tiene un impacto significativo al abordar el problema de forma integral. Esencialmente con cambios en el estilo de vida, al modificar la dieta incluyendo compuestos bioactivos que favorecen a la microbiota intestinal (MI) y un aumento de la actividad física. Debido al papel de la (MI) en la patogénesis del SMet, en los últimos años se han incorporado a la dieta probióticos y prebióticos individualmente o mezclados con alimentos o suplementos. La presente revisión define el papel de los prebióticos en la modificación de la microbiota para el tratamiento y la prevención de este padecimiento.
Article
The use of probiotic and synbiotic is a promising strategy to modulate the intestinal microbiota, and thereby modify the risk of diseases. In this study, the effect of probiotic VSL#3, isolated or associated with a yacon-based product (PBY), on the functional metabolic pathways of the microbiota, in a colorectal carcinogenesis model, was evaluated. For this, mice induced to carcinogenesis were fed with standard diet AIN-93M (CON), diet AIN-93M and VSL#3 (PRO) or diet AIN-93M with yacon and VSL#3 (SYN). The SYN group showed a highly differentiated intestinal community based on the MetaCyc pathways. Of the 351 predicted functional pathways, 222 differed between groups. Most of them were enriched in the SYN group, namely: amino acid biosynthesis pathways, small molecule biosynthesis pathways (cofactors, prosthetic groups, electron carriers and vitamins) carbohydrate degradation pathways and fermentation pathways. In addition, the synbiotic was able to stimulate the anti-inflammatory immune response and reduce the gene expression of PCNA and c-myc. Thus, we conclude that the synbiotic impacted more significantly the metabolic functions of the microbiota compared to the isolated use of probiotic. We believe that the enrichment of these pathways can exert antiproliferative action, reducing colorectal carcinogenesis. The prediction of the functional activity of the microbiota is a promising tool for understanding the influence of the microbiome on tumor development.
Article
Environmental issues associated with the widespread use of agricultural chemicals are being seriously concerned. Of them, toxicological impacts of fungicides in aquatic organisms are often overlooked. Here, soft-shelled turtle (Pelodiscus sinensis) hatchlings were exposed to different concentrations of vinclozolin (0, 5, 50, 500 and 5000 μg/L) for 60 days to investigate the impact of fungicide exposure on their gut microbial composition and diversity. Vinclozolin exposure significantly affected the composition of the gut microbiota in hatchling turtles. Unexpectedly, gut bacterial diversity and richness of vinclozolin-exposed turtles (but not for the 5000 μg/L-exposed group) were relatively higher than control ones. At the phylum level, the abundance of Firmicutes was decreased, while that of Proteobacteria was increased in high-concentration groups. At the genus level, some bacterial genera including Cellulosilyticum, Romboutsia and Clostridium_sensu_stricto, were significantly changed after vinclozolin exposure; and some uniquely observed in high-concentration groups. Gene function predictions showed that genes related to amino acid metabolism were less abundant, while those related to energy metabolism more abundant in high-concentration groups. The prevalence of some pathogens inevitably affected gut health status of vinclozolin-exposed turtles. Such gut microbiota dysbiosis might be potentially linked with hepatic metabolite changes induced by vinclozolin exposure.
Article
Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) is traditional Chinese medicine that has been used to treat diarrhea caused by acute enteritis (AE) and bacillary dysentery in Xinjiang (China) for many years. However, the potential therapeutic mechanism of MMRAC for AE and its regulatory mechanism on host metabolism is unclear. This study used fecal metabolomics profiling with GC/MS and 16S rRNA gene sequencing analysis to explore the potential regulatory mechanisms of MMRAC on a dextran sulfate sodium salt (DSS)-induced mouse model of AE. Fecal metabolomics-based analyses were performed to detect the differentially expressed metabolites and metabolic pathways. The 16S rRNA gene sequencing analysis was used to assess the altered gut microbes at the genus level and for functional prediction. Moreover, Pearson correlation analysis was used to integrate differentially expressed metabolites and altered bacterial genera. The results revealed that six intestinal bacteria and seven metabolites mediated metabolic disorders (i.e., metabolism of amino acid, carbohydrate, cofactors and vitamins, and lipid) in AE mice. Besides, ten altered microbes mediated the differential expression of eight metabolites and regulated these metabolisms after MMRAC administration. Overall, these findings demonstrate that AE is associated with metabolic disorders and microbial dysbiosis. Further, we present that MMRAC exerts protective effects against AE by improving host metabolism through the intestinal flora.
Article
Full-text available
Background Gut microbiota play a critical role in nutrition absorption and environmental adaptation and can affect the biological characteristics of host animals. The invasive golden apple snail ( Pomacea canaliculata ) and native Chinese mud snail ( Cipangopaludina chinensis ) are two sympatric freshwater snails with similar ecological niche in southern China. However, gut microbiota comparison of interspecies remains unclear. Comparing the difference of gut microbiota between the invasive snail P. canaliculata and native snail C. chinensis could provide new insight into the invasion mechanism of P.canaliculata at the microbial level. Methods Gut samples from 20 golden apple snails and 20 Chinese mud snails from wild freshwater habitats were collected and isolated. The 16S rRNA gene V3–V4 region of the gut microbiota was analyzed using high throughput Illumina sequencing. Results The gut microbiota dominantly composed of Proteobacteria, Bacteroidetes, Firmicutes and Epsilonbacteraeota at phylum level in golden apple snail. Only Proteobacteria was the dominant phylum in Chinese mud snail. Alpha diversity analysis (Shannon and Simpson indices) showed there were no significant differences in gut microbial diversity, but relative abundances of the two groups differed significantly ( P < 0.05). Beta diversity analysis (Bray Curtis and weighted UniFrac distance) showed marked differences in the gut microbiota structure ( P < 0.05). Unique or high abundance microbial taxa were more abundant in the invasive snail compared to the native form. Functional prediction analysis indicated that the relative abundances of functions differed significantly regarding cofactor prosthetic group electron carrier and vitamin biosynthesis, amino acid biosynthesis, and nucleoside and nucleotide biosynthesis ( P < 0.05). These results suggest an enhanced potential to adapt to new habitats in the invasive snail.
Article
Full-text available
Due to the ban on the use of antimicrobial growth promoters in livestock feeds, understanding the relationship between intestinal microbiota and the physiology of the host has become very important for improving livestock performance. In this study, we investigated the relationship between intestinal microbiota and body weights of weaned piglets. Lighter (n = 9) and heavier (n = 9) 9-week-old weaned piglets were selected from approximately one hundred individuals based on their body weights. Their fecal microbial communities were analyzed by sequencing the V4 region of the 16S rRNA gene. The microbial richness estimators of the heavier piglets were significantly higher than those of the lighter piglets. At the phylum level, the microbiota of the heavier group had significantly higher levels of Firmicutes and a higher Firmicutes-to-Bacteroidetes ratio than that of the lighter group. At the genus level, the levels of several genera, such as Anaerococcus and Lactococcus, were significantly different in the two groups. In particular, the lighter group had significantly higher levels of opportunistic pathogenic bacteria, such as Anaerotruncus and Bacteroides, compared with those of the heavier group. Moreover, the levels of bacteria expressing the components of several metabolic pathways were significantly different in the two groups. The microbiota of the heavier group had a significantly higher involvement in three KEGG pathways concerned with xenobiotic degradation than that of the lighter group. These results may provide insights into host-microbe interactions occurring in the piglet intestine and will be useful in establishing a strategy for improving growth performance in the swine industry.
Article
Full-text available
In-feed antibiotics have been used to promote growth in piglets, but its impact on metabolomics profiles associated with host metabolism is largely unknown. In this study, to test the hypothesis that antibiotic treatment may affect metabolite composition both in the gut and host biofluids, metabolomics profiles were analyzed in antibiotic-treated piglets. Piglets were fed a corn-soy basal diet with or without in-feed antibiotics from postnatal day 7 to day 42. The serum biochemical parameters, metabolomics profiles of the serum, urine, and jejunal digesta, and indicators of microbial metabolism (short-chain fatty acids and biogenic amines) were analyzed. Compared to the control group, antibiotics treatment did not have significant effects on serum biochemical parameters except that it increased (P < 0.05) the concentration of urea. Antibiotics treatment increased the relative concentrations of metabolites involved in amino-acid metabolism in the serum, while decreased the relative concentrations of most amino acids in the jejunal content. Antibiotics reduced urinary 2-ketoisocaproate and hippurate. Furthermore, antibiotics decreased (P < 0.05) the concentrations of propionate and butyrate in the feces. Antibiotics significantly affected the concentrations of biogenic amines, which are derived from microbial amino-acid metabolism. The three major amines, putrescine, cadaverine, and spermidine, were all increased (P < 0.05) in the large intestine of antibiotics-treated piglets. These results identified the phenomena that in-feed antibiotics may have significant impact on the metabolomic markers of amino-acid metabolism in piglets.
Article
Full-text available
Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection.
Article
Full-text available
There is a growing awareness that gut commensal metabolites play a major role in host physiology and indeed the pathophysiology of several illnesses. The composition of the microbiota largely determines the levels of tryptophan in the systemic circulation and hence, indirectly, the levels of serotonin in the brain. Some microbiota synthesize neurotransmitters directly, e.g., gamma-amino butyric acid, while modulating the synthesis of neurotransmitters, such as dopamine and norepinephrine, and brain-derived neurotropic factor (BDNF). The composition of the microbiota determines the levels and nature of tryptophan catabolites (TRYCATs) which in turn has profound effects on aryl hydrocarbon receptors, thereby influencing epithelial barrier integrity and the presence of an inflammatory or tolerogenic environment in the intestine and beyond. The composition of the microbiota also determines the levels and ratios of short chain fatty acids (SCFAs) such as butyrate and propionate. Butyrate is a key energy source for colonocytes. Dysbiosis leading to reduced levels of SCFAs, notably butyrate, therefore may have adverse effects on epithelial barrier integrity, energy homeostasis, and the T helper 17/regulatory/T cell balance. Moreover, dysbiosis leading to reduced butyrate levels may increase bacterial translocation into the systemic circulation. As examples, we describe the role of microbial metabolites in the pathophysiology of diabetes type 2 and autism.
Article
Full-text available
The gut microbiota has been proposed as an environmental factor that promotes the progression of metabolic diseases. Here, we investigated how the gut microbiota modulates the global metabolic differences in duodenum, jejunum, ileum, colon, liver, and two white adipose tissue depots obtained from conventionally raised (CONV-R) and germ-free (GF) mice using gene expression data and tissue-specific genome-scale metabolic models (GEMs). We created a generic mouse metabolic reaction (MMR) GEM, reconstructed 28 tissue-specific GEMs based on proteomics data, and manually curated GEMs for small intestine, colon, liver, and adipose tissues. We used these functional models to determine the global metabolic differences between CONV-R and GF mice. Based on gene expression data, we found that the gut microbiota affects the host amino acid (AA) metabolism, which leads to modifications in glutathione metabolism. To validate our predictions, we measured the level of AAs and N-acetylated AAs in the hepatic portal vein of CONV-R and GF mice. Finally, we simulated the metabolic differences between the small intestine of the CONV-R and GF mice accounting for the content of the diet and relative gene expression differences. Our analyses revealed that the gut microbiota influences host amino acid and glutathione metabolism in mice.
Article
Full-text available
Disruptions in gut microbiota composition and function are increasingly implicated in the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus. The functional output of the gut microbiota, including short-chain fatty acids and amino acids, are thought to be important modulators underlying the development of these disorders. Gut bacteria can alter the bioavailability of amino acids by utilization of several amino acids originating from both alimentary and endogenous proteins. In turn, gut bacteria also provide amino acids to the host. This could have significant implications in the context of insulin resistance and type 2 diabetes mellitus, conditions associated with elevated systemic concentrations of certain amino acids, in particular the aromatic and branched-chain amino acids. Moreover, several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids, which also play a role in the development of obesity. In this review, we aim to compile the available evidence on the contribution of microbial amino acids to host amino acid homeostasis, and to assess the role of the gut microbiota as a determinant of amino acid and short-chain fatty acid perturbations in human obesity and type 2 diabetes mellitus.
Article
This article has been removed: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The publisher regrets that an error occurred due to a technical issue which led to the premature publication of this paper. This error bears no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error.
Article
Hepatocyte transplantation aims to provide a functional substitution of liver tissue lost due to trauma or toxins. Chronic liver diseases are associated with inflammation, deterioration of tissue homeostasis, and deprivation of metabolic capacity. Recent advances in liver biology have focused on the pro-regenerative features of mesenchymal stem cells (MSCs). We argue that MSCs represent an attractive therapeutic option to treat liver disease. Indeed, their pleiotropic actions include the modulation of immune reactions, the stimulation of cell proliferation, and the attenuation of cell death responses. These characteristics are highly warranted add-ons to their capacity for hepatocyte differentiation. Undoubtedly, the elucidation of the regenerative mechanisms of MSCs in different liver diseases will promote their versatile and disease-specific therapeutic use.
Article
Intestinal microbiota changes may be involved in the development of metabolic syndrome (MetS), which is a multicomponent disorder frequently associated with obesity. The aim of this study was to test the effect of consuming two healthy diets: a Mediterranean diet and a low-fat high-carbohydrate diet, for 2years in the gut microbiota of MetS patients and those in the control group. We analyzed the differences in the bacterial community structure between the groups after 2years of dietary intervention (Mediterranean or low-fat diet) through quantitative polymerase chain reaction using primers, targeting specific bacterial taxa. We observed, at basal time, that the abundance of Bacteroides, Eubacterium and Lactobacillus genera is higher in the control group than in MetS patients, while Bacteroides fragilis group, Parabacteroides distasonis, Bacteroides thetaiotaomicron, Faecalibacterium prausnitzii, Fusobacterium nucleatum, Bifidobacterium longum, Bifidobacterium adolescentis, Ruminococcus flavefaciens subgroup and Eubacterium rectale are depleted in MetS patients (all P values <.05). Additionally, we found that long-term consumption of Mediterranean diet partially restores the population of P. distasonis, B. thetaiotaomicron, F. prausnitzii, B. adolescentis and B. longum in MetS patients (all P values <.05). Our results suggest that the Mediterranean diet could be a useful tool to restore potentially beneficial members of the gut microbiota, although the stability of these changes over time still remains to be assessed.