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 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities that are associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes and by mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this review, we focus on studies in humans to describe these challenges and propose strategies that leverage existing knowledge to move rapidly from correlation to causation and ultimately to translation into therapies.
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PMID:Current understanding of the human microbiome. 2963 82

Existing methods of clustering of gut microbiota (enterotypes, clusters, gradients), as well as the term 'phylogenetic core' do not reflect its functional activity. The authors propose to describe the key microbiora using term 'phylometabolic core of intestinal microbioca which more accurately reflects the functional importance of metabolically active microbiota. Phylometabolic core includes functional groups of microorganisms that perform similar metabolic functions: butyrate-producing bacteria, propionate-producing bacteria, acetate-produc- ing bacteria (acerogens), hydrogenosrophic microorganisms (reductive acetogens, sulfate-reducing bacteria, methanogens), lactate-producing and lactate-utilizing bacteria, bacteria involved in bile acids metabolism, bacteria that metabolize proteins and amino acids, vitamin-producing microorganisms, oxalate-degrading bacteria and others. The hypothesis that disturbance of microbial metabolism is the root of many human diseases is discussed. The microbial dysmexabo- lism leads to the metabolic dysbiosis (a particular form of dysbiosis) that is primarily characterized by metabolic abnormalities (e.g. serum, urinary, fetal or exhaled air). Metabolic dysbiosis is not necessarily accompanied by appreciable quantitative and/or qualitative changes in microbiora composition that called taxonomic dysbiosis. Since in the metabolic dysbiosis metabolic pathways can be switched only, it means the need for completely different approaches to its assessment using metabolomics (metabolic fingerprinting, metabolic profiling, meta-metabolomics). Metabolites concentrations in colon (feces, biopsy samples), blood (serum, plasma), urine or exhaled air, as well as metabolic profiles of examined substrates can serve as biomarkers. The main clinical variants of metabolic dysbiosis are due to the disturbances in microbial synthesis of short-chain fatty acids (primarily butyrate and propionate) and due to increasing bacterial production of hydrogen sulfide, ammonia and secondary bile acids (particularly deoxycholic acid). These kinds of metabolic dysbiosis can eventually lead to inflammatory bowel disease (IBD) or colorectal cancer (CRC). The metabolic dysbiosis due to bacterial choline dysmetabolism followed by overproduction of trimethylamine (TMA), arherogenic precursor of trimethylamine N-oxide (TMAO), is associated with atherogenesis and increased risk of cardiovascular disease. Dysmetabolism of aromatic amino acids leads to changes in the microbial production of phenylalanine and tyrosine derivatives (phenyl carboxylic acid, p-cresol) and tryptophan indole derivatives (indole carboxylic acid, indole) and contributes to pathogenesis in lBS. IBD, CRC, chronic liver and kidney diseases, cardiovascular diseases, autism and schizophrenia. Metabiotics, a new class of therapeutic agents, e.g. based on microbial metabolites, can correct metabolic dysbiosis, prevent diet- and microbiota-relared diseases and increase the effectiveness of treatment.
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PMID:METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS. 2988 18

Mycobacterium avium subspecies paratuberculosis is a bacterial parasite and the causative agent of paratuberculosis, a disease predominately found in cattle and sheep. Infection with this microorganism results in substantial farming economic losses and animal morbidity. The link between infection with this pathogen and human disease has been theorised for many years with Crohn's disease being one of many suspected resultant conditions. Mycobacterium avium may be spread from animal to human hosts by water and foodborne transmission routes, where the foodborne route of exposure represents a significant risk for susceptible populations, namely children and the immune-compromised. Following colonisation of the host, the parasitic organism evades the host immune system by use of molecular mimicry, displaying peptide sequences similar to that of the host cells causing a disruption of self-verses non self-recognition. Theoretically, this failure to recognise the invading organism as distinct from host cells may result in numerous autoimmune conditions. Here, the author presents current information assessing the link between numerous diseases states in humans such inflammatory bowel disease, Type 1 diabetes, rheumatoid arthritis, Hashimoto\'s thyroiditis, multiple sclerosis and autism following infection with Mycobacterium avium paratuberculosis. The possibility of zoonotic transmission of the organism and its significant risk to public health safety as a consequence is also discussed.
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PMID:Mycobacterium avium subspecies paratuberculosis: A possible causative agent in human morbidity and risk to public health safety. 2991 Oct 21

The epithelial lining of the gastrointestinal tract serves as the interface for digestion and absorption of nutrients and water and as a defensive barrier. The defensive functions of the intestinal epithelium are remarkable considering that the gut lumen is home to trillions of resident bacteria, fungi and protozoa (collectively, the intestinal microbiota) that must be prevented from translocation across the epithelial barrier. Imbalances in the relationship between the intestinal microbiota and the host lead to the manifestation of diseases that range from disorders of motility and sensation (IBS) and intestinal inflammation (IBD) to behavioural and metabolic disorders, including autism and obesity. The latest discoveries shed light on the sophisticated intracellular, intercellular and interkingdom signalling mechanisms of host defence that involve epithelial and enteroendocrine cells, the enteric nervous system and the immune system. Together, they maintain homeostasis by integrating luminal signals, including those derived from the microbiota, to regulate the physiology of the gastrointestinal tract in health and disease. Therapeutic strategies are being developed that target these signalling systems to improve the resilience of the gut and treat the symptoms of gastrointestinal disease.
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PMID:Neuroimmunophysiology of the gut: advances and emerging concepts focusing on the epithelium. 3006 36

The number of bacterial cells living within the human body is approximately equal to, or greater than, the total number of human cells. This dynamic population of microorganisms, termed the human microbiota, resides mainly within the gastrointestinal tract. It is widely accepted that highly diverse and stable microbiota promote overall human health. Colonization of the gut with maladaptive and pathogenic microbiota, a state also known as dysbiosis, is associated with a variety of peripheral diseases ranging from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease. More recently, microbial dysbiosis has been associated with a number of brain pathologies, including autism spectrum disorder, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), suggesting a direct or indirect communication between intestinal bacteria and the central nervous system (CNS). In this review, we illustrate two pathways implicated in the crosstalk between gut microbiota and CNS involving 1) the vagus nerve and 2) transmission of signaling molecules through the circulatory system and across the blood-brain barrier (BBB). We summarize the available evidence of the specific changes in the intestinal microbiota, as well as microorganism-induced modifications to intestinal and BBB permeability, which have been linked to several neurodegenerative disorders including ALS, AD, and PD. Even though each of these diseases arises from unique pathogenetic mechanisms, all are characterized, at least in part, by chronic neuroinflammation. We provide an interpretation for the substantial evidence that healthy intestinal microbiota have the ability to positively regulate the neuroimmune responses in the CNS. Even though the evidence is mainly associative, it has been suggested that bacterial dysbiosis could contribute to an adverse neuroinflammatory state leading to increased risk of neurodegenerative diseases. Thus, developing strategies for regulating and maintaining healthy intestinal microbiota could be a valid approach for lowering individual risk and prevalence of neurodegenerative diseases.
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PMID:Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases. 3011 73

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.
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PMID:The Human Gut Microbiome - A Potential Controller of Wellness and Disease. 3015 67

Research into the influence of the microbiome on the human body has been shedding new light on diseases long known to be multifactorial, such as obesity, mood disorders, autism, and inflammatory bowel disease. Although inborn errors of metabolism (IEMs) are monogenic diseases, genotype alone is not enough to explain the wide phenotypic variability observed in patients with these conditions. Genetics and diet exert a strong influence on the microbiome, and diet is used (alone or as an adjuvant) in the treatment of many IEMs. This review will describe how the effects of the microbiome on the host can interfere with IEM phenotypes through interactions with organs such as the liver and brain, two of the structures most commonly affected by IEMs. The relationships between treatment strategies for some IEMs and the microbiome will also be addressed. Studies on the microbiome and its influence in individuals with IEMs are still incipient, but are of the utmost importance to elucidating the phenotypic variety observed in these conditions.
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PMID:The microbiome and inborn errors of metabolism: Why we should look carefully at their interplay? 3023 99

Tryptophan is an essential plant-derived amino acid that is needed for the in vivo biosynthesis of proteins. After consumption, it is metabolically transformed to bioactive metabolites, including serotonin, melatonin, kynurenine, and the vitamin niacin (nicotinamide). This brief integrated overview surveys and interprets our current knowledge of the reported multiple analytical methods for free and protein-bound tryptophan in pure proteins, protein-containing foods, and in human fluids and tissues, the nutritional significance of l-tryptophan and its isomer d-tryptophan in fortified infant foods and corn tortillas as well the possible function of tryptophan in the diagnosis and mitigation of multiple human diseases. Analytical methods include the use of acid ninhydrin, near-infrared reflectance spectroscopy, colorimetry, basic hydrolysis; acid hydrolysis of S-pyridylethylated proteins, and high-performance liquid and gas chromatography-mass spectrometry. Also covered are the nutritional values of tryptophan-fortified infant formulas and corn-based tortillas, safety of tryptophan for human consumption and the analysis of maize (corn), rice, and soybean plants that have been successfully genetically engineered to produce increasing tryptophan. Dietary tryptophan and its metabolites seem to have the potential to contribute to the therapy of autism, cardiovascular disease, cognitive function, chronic kidney disease, depression, inflammatory bowel disease, multiple sclerosis, sleep, social function, and microbial infections. Tryptophan can also facilitate the diagnosis of certain conditions such as human cataracts, colon neoplasms, renal cell carcinoma, and the prognosis of diabetic nephropathy. The described findings are not only of fundamental scientific interest but also have practical implications for agriculture, food processing, food safety, nutrition, and animal and human health. The collated information and suggested research need will hopefully facilitate and guide further studies needed to optimize the use of free and protein-bound tryptophan and metabolites to help improve animal and human nutrition and health.
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PMID:Analysis, Nutrition, and Health Benefits of Tryptophan. 3027

Cow's milk allergy (CMA) is an early-onset allergy of which the underlying genetic factors remain largely undiscovered. CMA has been found to co-occur with other allergies and immunological hypersensitivity disorders, suggesting a shared genetic etiology. We aimed to (1) investigate and (2) validate whether CMA children carry a higher genetic susceptibility for other immunological hypersensitivity disorders using polygenic risk score analysis (PRS) and prospective phenotypic data. Twenty-two CMA patients of the Dutch EuroPrevall birth cohort study and 307 reference subjects were genotyped using single nucleotide polymorphism (SNP) array. Differentially genetic susceptibility was estimated using PRS, based on multiple P-value thresholds for SNP inclusion of previously reported genome-wide association studies (GWAS) on asthma, autism spectrum disorder, atopic dermatitis, inflammatory bowel disease and rheumatoid arthritis. These associations were validated with prospective data outcomes during a six-year follow-up in 19 patients. We observed robust and significantly higher PRSs of asthma in CMA children compared to the reference set. Association analyses using the prospective data indicated significant higher PRSs in former CMA patients suffering from asthma and related traits. Our results suggest a shared genetic etiology between CMA and asthma and a considerable predictive sensitivity potential for subsequent onset of asthma which indicates a potential use for early clinical asthma intervention programs.
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PMID:Higher Polygenetic Predisposition for Asthma in Cow's Milk Allergic Children. 3037 30

All natural animals and plants are holobionts, consisting of the host and microbiome, which is composed of abundant and diverse microorganisms. Health and disease of holobionts depend as much on interactions between host and microbiome and within the microbiome, as on interactions between organs and body parts of the host. Recent evidence indicates that a significant fraction of the microbiome is transferred by a variety of mechanisms from parent to offspring for many generations. Genetic variation in holobionts can occur in the microbiome as well as in the host genome, and it occurs more rapidly and by more mechanisms in genomes of microbiomes than in host genomes (e.g. via acquisition of novel microbes and horizontal gene transfer of microbial genes into host chromosomes). Evidence discussed in this review supports the concept that holobionts with their hologenomes can be considered levels of selection in evolution. Though changes in the microbiome can lead to evolution of the holobiont, it can also lead to dysbiosis and diseases (e.g. obesity, diarrhea, inflammatory bowel disease, and autism). In practice, the possibility of manipulating microbiomes offers the potential to prevent and cure diseases.
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PMID:The Hologenome Concept of Evolution: Medical Implications. 3072 Apr 24


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