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Trends in human microbiome research over the last decade: PubMed Citations by year using search term ‘Human microbiome’. Y-axis: number of publications. 

Trends in human microbiome research over the last decade: PubMed Citations by year using search term ‘Human microbiome’. Y-axis: number of publications. 

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The human gut microbiota is a complex microbial ecosystem that contributes an important component towards the health of its host. This highly complex ecosystem has been underestimated in its importance until recently, when a realization of the enormous scope of gut microbiota function has been (and continues to be) revealed. One of the more strikin...

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... recent years, research into the human microbiome I has much captured in the same the imagination way that human of the genome general research public, permeated public consciousness at the start of the new millennium. As a field of study, human microbiome research has exploded in the last decade ( Fig. 1), which has led to a new awareness of the importance of these associated microbes to our overall health. This came as somewhat of a shock to those of us who were raised to think of all microbes as ‘germs’ to be eradicated; instead, we are beginning to see ourselves as microbe managers, tend- ing to the needs of our microbial ‘employees’ for mutual benefit. This short review discusses how human-associated microbes Á particularly those in the gut Á affect health, and how the widespread phenomenon of gut microbial ‘dysbiosis’ could be driving an epidemic of chronic disease, which may include autism spectrum disorder (ASD). Until recently, babies were believed to be born sterile and only populated by microbes on exposure to their first ...

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This article aims to provide a thorough overview of the use of Artificial Intelligence (AI) techniques in studying the gut microbiota and its role in the diagnosis and treatment of some important diseases. The association between microbiota and diseases, together with its clinical relevance, is still difficult to interpret. The advances in AI techn...
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Many childhood diseases such as autism spectrum disorders, allergic disease, and obesity are on the increase. Although environmental factors are thought to play a role in this increase. The mechanisms at play are unclear but increasing evidence points to an interaction with the gastrointestinal microbiota as being potentially important. Recently th...

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... The results of these studies show several genera present in larger quantities in ASD, such as Bacteroides, Roseburia, Akkermansia, Hespellia spp. and others with smaller amounts, such as Prevotella and bifidobacteria [16]. There are no studies evaluating the effect of GFCF dietary approaches on GM in ASD individuals. ...
Article
Autism is a complex disorder without a specific diagnosis, so the disease is defined by its specific characteristics described in the literature as cognitive defects, social, communication and behavioral problems, repetitive behaviors, unusual sensitivity to stimuli such as noise, restricted interests, and self stimulation. There are many models in the literature explaining the biology of autism, which are based on genetics, immunity, various environmental factors and diet. There is a lot of literature data that people with Autism Spectrum Disorders (ASD) often have gastrointestinal problems that also affect their behavior. ASD suffer developmental disabilities from an early age, which can be both physical and psychological. Often people suffer these problems even throughout their lives. This review aims to provide basic information on definitions, historical data, diagnostic methods, behavioral etiology, gastrointestinal and social problems in adults and children with ASD.
... In contrast, the imbalance, also called dysbiosis, can be a predisposing factor for the occurrence of diseases, such as enterocolitis (Harlow, 2013;Schoster et al., 2017;De La Torre et al., 2018), laminitis (Steelman et al, 2012;Moreau, 2014), colic , and, in humans it has been associated with several other diseases (Gosalbes et al,. 2012;Toh and Allen-vercoe, 2015;Wang et al., 2018). ...
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Horses are extremely dependent on the correct functioning of the digestive system for energy production and the performance of their physiological functions. The intestinal microbiota plays a key role in maintaining health, being related to the modulation of the immune system, protection against pathogenic microorganisms and also for obtaining nutrients. Due to the importance of the microbiota in maintaining health from the beginning of life, this review aims to address the early composition, development and factors that influence the intestinal microbiota in foals. A qualitative review was carried out in the main research databases. Data referring to the early microbial colonization suggest that it occurs since intrauterine life, despite the fact that at birth, the foals acquire a large part of the microorganisms that will form its microbiota. The main phyla involved in this process are Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes, which are aquired from a combination of bacteria present in the feces, vagina and other maternal environments. From birth until the first weeks of life, the microbiota gradually changes due to several factors, which include the composition of food, coprophagy, exposure to different environments and medications. The foal's microbiota becomes more stable in the first and second months of life. It is suggested that changes in the composition (dysbiosis) and diversity of the different phyla are a risk factor for the development of diseases, since the microbiota directly influences the immune system. From advances in sequencing technologies it was possible to investigate the components and factors associated with early colonization of microbiota in horses as well as factors related to the development of dysbiosis and disease. Nevertheless, many facts are still unclear and should be adressed in the future.
... The human microbiome is a rapidly expanding area of clinical research. Scientific literature examining the role of the microbiome in human health has increased substantially over the last ten years [1]. This has led to the identification of the microbiome as a major contributor to human health and disease [2]. ...
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Purpose Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. Methods This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. Results Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. Conclusions Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.
... Clinical studies showed that gastrointestinal symptoms often occur in ASD children, and their severity is related to the degree of behavioral disorders (5,6). The pathogenesis of ASD is not clear, but it has proved to be related to the gut microbiota (7,8). Other studies found differences in intestinal microbial communities between ASD children and control groups (5,(9)(10)(11). ...
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Background: Autism spectrum disorders (ASD) is a complex neurodevelopmental disorder that lacks an ideal animal model to recapitulate the disease state of ASD. Previous studies have reported that transplanting gut microbiota of ASD patients into pregnant mice is sufficient to promote the changes of autism-like behavior in offspring. This study aims to explore whether fecal microbiota transplantation (FMT) can be used as a new method to establish the ASD animal model. Methods: We transplanted the fecal sample extract of ASD children into pregnant rats (rFMT) repeatedly to establish an ASD rat model (oFMT) and compare it with the classical valproic acid (VPA) model (oVPA). Results: First, we reveal that oFMT shows hypoevolutism and typical behavioral characteristics of ASD, consistent with the previous study. Second, the gut microbiota of oFMT mainly consists of Firmicutes and Bacteroidetes, recapitulating the abnormal gut microbiota of ASD. In oFMT, the abundance of Lactobacillus and Collinsella increased (Lactobacillus: oFMT 60.16%, oVPA 64.13%, oCON 40.11%; Collinsella: oFMT 3.73%, oVPA 1.39%, oCON 1.28%), compared with oVPA, gut microbiota also showed high consistency. Third, the expression of 5-hydroxytryptamine (5-HT) in oFMT serum increased, γ-aminobutyric acid (GABA) and norepinephrine (NE) in oFMT serum decreased. Fourth, the gut microbiota of oFMT also has some ASD characteristic gut microbiota not found in oVPA. Fifth, pregnant rat with VPA showed significant immune activation, while those with FMT showed relatively minor immune activation. Limitations: Although the mechanism of establishing FMT autism rat model (oFMT) has not clearly defined, the data show that the model has high structural validity, and FMT model is likely to be a new and reliable potential animal model of ASD, and will have potential value in studying gut microbiota of ASD. Conclusions: The FMT autism rat model has high structural validity, and the FMT model is likely to be a new and reliable potential animal model of ASD.
... Nevertheless, the molecular mechanism(s) of this interaction is yet to be explained. These finding implies a role of GMB in human behavior and mental health [17], via direct or indirect influence on the host immune system and the metabolism [18]. ...
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Gut microbiota has become an issue of great importance recently due to its major role in autism spectrum disorder (ASD). Over the past three decades, there has been a sustained research activity focused to explain the actual mechanism by which gut microbiota triggers/develops autism. Several genetic and epigenetic factors are involved in this disorder, with epigenetics being the most active area of research. Although the constant investigation and advancements, epigenetic implications in ASD still need a deeper functional/causal analysis. In this review, we describe the major gut microbiota metabolites and how they induce epigenetic changes in ASD along with interactions through the gut-brain axis.
... The gut microbiome is important for immune response, gastrointestinal tract health, endocrine system functioning, behavior, and even cognitive function in both humans and animals [1][2][3][4][5][6]. In humans, gut dysbiosis has been linked to many conditions, including obesity, autism spectrum disorders, diabetes, colorectal cancer, inflammatory bowel diseases as well as diseases caused by pathogenic bacteria [7][8][9][10]. In the horse, common gastrointestinal disorders have been associated with gut dysbiosis, including starch-induced laminitis, colitis, diarrhea and gastric ulcers [11][12][13][14][15]. ...
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Background Early development of the gut microbiome is an essential part of neonate health in animals. It is unclear whether the acquisition of gut microbes is different between domesticated animals and their wild counterparts. In this study, fecal samples from ten domestic conventionally managed (DCM) Standardbred and ten semi-feral managed (SFM) Shetland-type pony foals and dams were compared using 16S rRNA sequencing to identify differences in the development of the foal hindgut microbiome related to time and management. Results Gut microbiome diversity of dams was lower than foals overall and within groups, and foals from both groups at Week 1 had less diverse gut microbiomes than subsequent weeks. The core microbiomes of SFM dams and foals had more taxa overall, and greater numbers of taxa within species groups when compared to DCM dams and foals. The gut microbiomes of SFM foals demonstrated enhanced diversity of key groups: Verrucomicrobia (RFP12), Ruminococcaceae, Fusobacterium spp., and Bacteroides spp., based on age and management. Lactic acid bacteria Lactobacillus spp. and other Lactobacillaceae genera were enriched only in DCM foals, specifically during their second and third week of life. Predicted microbiome functions estimated computationally suggested that SFM foals had higher mean sequence counts for taxa contributing to the digestion of lipids, simple and complex carbohydrates, and protein. DCM foal microbiomes were more similar to their dams in week five and six than were SFM foals at the same age. Conclusions This study demonstrates the impact of management on the development of the foal gut microbiome in the first 6 weeks of life. The higher numbers of taxa within and between bacterial groups found in SFM dams and foals suggests more diversity and functional redundancy in their gut microbiomes, which could lend greater stability and resiliency to these communities. The colonization of lactic acid bacteria in the early life of DCM foals suggests enrichment in response to the availability of dams’ feed. Thus, management type is an important driver of gut microbiome establishment on horses, and we may look to semi-feral horses for guidance in defining a healthy gut microbiome for domestic horses.
... Finegold et al. [26] noted an increase of Desulfovibrio spp. and Wang et al. [27] have observed higher levels of Sutterella and Ruminococcus spp. in individuals with ASD compared to control [28,29]. These gut bacteria produce short-chain fatty acids (SCFAs) such as propanoic acid (PPA) as a consequence of metabolism of dietary carbohydrates as well as amino acids [30]. ...
... They have abnormal gut flora. It has been observed that gut bacteria such as Clostridia, Desulfovibrio, Sutterella, and Ruminococcus species produce short-chain fatty acids (SCFAs) such as PPA because of the metabolism of dietary carbohydrates and amino acids [26,27,29,30]. Propanoic acid (PPA) is responsible for the generation of pro-inflammatory cytokines like TNF-α, IL-6, INF-ϒ and the reduction in the levels of endogenous antioxidants such as glutathione, superoxide dismutase as well the elevation of lipid peroxidase [41]. ...
... Immune system deregulation, neuroinflammation, environmental toxicant exposures, oxidative stress, mitochondrial dysfunction and gastrointestinal complications are physiological comorbidities occurring in individuals with autism spectrum disorders (ASD) [18,19,21,69] and can worsen behavioral complications. Gastrointestinal complications can lead to immune system dysregulation and result in generation of oxidative stress due to generation of short-chain fatty acids by abnormal gut flora [29]. This leads to synthesis of various pro-inflammatory cytokines and chemokines causing activation of microglia. ...
Chapter
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with symptoms ranging from lack of social interaction and communication deficits to rigid, repetitive, and stereotypic behavior. It has also been associated with comorbidities such as anxiety, aggression, epilepsy, deficit in sensory processing, as well as ADHD (attention deficit hyperactivity disorder). Apart from several behavioral and cognitive complications arising as a result of central nervous system dysfunction, there are various physiological comorbidities such as immune system deregulation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and gastrointestinal complications which can worsen existing behavioral complications. There are no available treatments for these physiological comorbidities. The prevalence of gastrointestinal complications in ASD ranges from 9% to 70% and it correlates with behaviors consistent with the autistic endophenotype indicating that these are one of the major comorbidities associated with ASD. A strong connection of gut–brain cross talk occurs as a result of gut dysbiosis responsible for excessive production of short-chain fatty acids such as propanoic acid (PPA) by abnormal gut flora in ASD patients. This worsens behavioral, neurochemical, and mitochondrial dysfunction occurring in ASD. These physiological comorbidities are responsible for the generation of free radical species that cause immune system dysfunction leading to synthesis of various pro-inflammatory cytokines and chemokines. This in turn causes activation of microglia. Dietary phytochemicals are thought to be safer and useful as an alternative neurotherapeutic moiety. These compounds provide neuroprotection by modulating signaling pathways such as Nrf2, NF-κB, MAPK pathway or Sirtuin-FoxO pathway. There has been recent evidence in scientific literature regarding the modulation of gut–brain cross talk responsible for behavioral, biochemical, and mitochondrial dysfunction as well as cellular and behavioral sensory alterations by dietary phytochemicals such as curcumin, resveratrol, naringenin, and sulforaphane. These dietary phytochemicals can be formulated in novel brain-targeted delivery systems which overcome their limitation of low oral bioavailability and short half-life leading to prolonged action. Till date, not much work has been done on the development of brain-targeted neurotherapeutics for ASD. In this chapter we discuss plausible mechanisms and evidence from our own and other scientific research for the utilization of curcumin, resveratrol, naringenin, and sulforaphane as neurotherapeutics for ASD.
... These are dynamical projects, which can be continuously improved by ongoing researches, an advantage that could turn into a disadvantage in some cases when combining dissimilar datasets [87]. Developing such databases will permit using the data on gut microbiota and brain-gastrointestinal interactions in the larger context of the host genetics and epigenetics variability, and may offer a new view on the etiology of ASD [90]. ...
Article
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Background and Objectives: Gastrointestinal disturbances have been frequently, but not unanimously, reported in autism spectrum disorder (ASD) individuals. Thus, digestive symptoms, such as constipation, diarrhea, abdominal bloating, and pain have been reported to correlate to the various maladaptive behaviors in ASD children, such as irritability, social withdrawal, stereotypy, hyperactivity, and even language regression. In this context, the present study provides an overview on the prevalence of the gastrointestinal (GI) disorders in ASD and the correlation between these and ASD symptoms and comorbidities and subsequently discusses the metabolic and microbiome factors underlying the effects of GI disorders in ASD. Materials and Methods: For our analysis of GI symptoms in children with ASD, we have searched peer-reviewed journals from 2005 to 2017 in PubMed databases that addressed the specificity of GI symptoms in ASD and included correlations of GI and ASD symptoms. The criteria for inclusion were clear quantitative mentioning of GI modifications, GI symptoms correlation with specific ASD symptoms or comorbidities, an appropriate methodology for defining ASD, and larger size samples. For this topic, only studies on human patients and original research were considered. A subsequent search in PubMed databases in journals from 2000 to 2017 we analyzed 13 articles on the mechanisms underlying the impact of GI dysfunctions in ASD, including gut microbial dysbiosis, immune reactivity, genetics, and altered neurotransmitters on the gut–brain axis. Results: In the 18 original research studies that we selected out of an initial 327 studies, despite the different methodology, a predominant 83% highlighted the increased prevalence of GI symptoms in ASD patients. Constipation was most frequently cited, appearing in 12 of the studies (80%), followed by diarrhea reports in eight studies (53%). The association between cognitive and behavioral deficits and GI disorders was suggested in certain groups of ASD individuals. Conclusion: The evidence presented so far by numerous studies seems to indicate that GI dysfunctions are of particular relevance in ASD, underlined by various abnormalities along the nervous connections between the central nervous system and the gut, such as impaired parasympathetic activity and increased endocrine stress response. Sufficiently large size samples and standardized methodology are required for future studies to clarify the complex interactions between GI disturbances and ASD symptoms.
... Ilya Ilyich (Elie) Metchnikoff, un chercheur russe, peut être considéré comme l'un des premiers scientifiques à avoir participé activement à ce processus. De (Toh and Allen-Vercoe 2015). Une deuxième caractéristique de l'épithélium favorise les échanges : ...
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L’intestin est un système complexe qui joue un rôle fondamental dans l’absorption et la distribution des nutriments nécessaires aux différents organes d’un organisme, comme par exemple le glucose pour le cerveau. Finement régulé par le système nerveux, le système digestif abrite également un acteur qui joue un rôle crucial : la flore intestinale − ancien terme désignant le “microbiote” − qui pèse autant que le cerveau lui-même ! Comme le tractus gastro-intestinal est également exposé à des risques d’invasion par des agents pathogènes, un quatrième intervenant joue un rôle clé : le système immunitaire. Ce dernier exerce une surveillance étroite du tractus gastrointestinal et joue un rôle important dans les interactions entre l’intestin et le cerveau, pour le meilleur ou pour le pire... Qu’il s’agisse de l’intestin ou du cerveau, ces deux organes sont isolés du reste du corps par des barrières dont le bon fonctionnement est vital, prémunissant l’organisme et sa commande centrale cérébrale de mécanismes infectieux qui pourraient lui être fatals. Et pourtant… Des voies les relient, qui participent au dialogue entre − mais aussi à la vulnérabilité de − ces divers protagonistes de différentes façons. Le paysage physiologique humain est donc un amalgame complexe de cellules humaines mais également de cellules bactériennes qui collaborent étroitement au contrôle de la santé humaine. Non seulement le microbiote est capable de digérer certains nutriments qui ne peuvent pas être dégradés par le tractus gastro-intestinal lui-même, mais un nombre croissant d’études scientifiques suggère un lien entre la fonction gastro-intestinale (GI) et la fonction cérébrale − et par là même une association avec certaines maladies neurologiques et psychiatriques. Ainsi, on soupçonne que l’axe intestin-cerveau est impliqué dans un certain nombre de maladies psychiatriques ou neuroimmunes chez l’enfant et l’adulte, dont les troubles du spectre autistique (TSA), le trouble déficitaire de l’attention avec hyperactivité (TDAH), la schizophrénie, les troubles de l’humeur, la dépression et la sclérose en plaques. De plus, il a été suggéré que les troubles intestinaux constituent un “facteur de risque” pour le développement de troubles neurologiques tels que la maladie de Parkinson ou la maladie d’Alzheimer. Enfin, et non des moindres, le stress régule la composition et l’activité de la flore intestinale, une propriété qui pourrait même affecter la santé psychiatrique à travers les générations. C’est ainsi qu’est né le concept d’« axe intestin-cerveau » selon lequel il existe un dialogue constant entre l’intestin et le cerveau. En tant que tels, les animaux vivants ne devraient plus être considérés comme des êtres auto-suffisants, mais plutôt comme un paysage complexe dans lequel les microbes constituent la pierre angulaire de cet équilibre. C’est la fabuleuse histoire de l’axe intestincerveau- microbiote, un véritable écosystème dans lequel des échanges fructueux pourraient conditionner l’équilibre neurologique et psychiatrique de l’être humain et dont nous allons aborder quelques uns des secrets de fonctionnement…
... Several chronic diseases have been associated with a GI tract limited in microorganism diversity [5], but it is difficult to determine whether the decreased biotic diversity is due to the disease or vice-versa. Along these lines, it has been observed that ASD patients also have abnormal GI bacterial flora compared to developmentally normal children [6]. ...
... Along these lines, it has been observed that ASD patients also have abnormal GI bacterial flora compared to developmentally normal children [6]. It has been demonstrated that switching the gut microbiota of a timid mouse line with a more aggressive mouse line resulted in a concurrent switch of the behavioral profiles of the mice [5,7]. [8,9]. ...
... Although still at early stages, investigations into the relationship between the human gut microbiome and health have revealed interesting findings, especially those that are related to a likely association between gut-flora compositions and neurological disorders, in a so-called 'gut-brain' axis [36]. One of the most intriguing findings has been the detection of a set of gut bacteria in autistic patients, which also suffer from GI disorders [5]. These gut pathogens, especially Clostridia pathogens, excrete metabolites, such as short-chain fatty-acids, that cross the brain barrier, and are believed to act as neurotoxins instigating autismlike symptoms, especially during early stages of brain development [5]. ...
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A large number of children in the autism spectrum disorder suffer from gastrointestinal (GI) conditions, such as constipation and diarrhea. Clostridium bolteae is part of a set of pathogens being regularly detected in the stool samples of hosts affected by GI and autism symptoms. Accompanying studies have pointed to the possibility that such microbes affect behaviour through the production of neurotoxic metabolites in a so-called, gut-brain connection. As an extension of our Clostridium difficile polysaccharide (PS)-based vaccine research, we engaged in the discovery of C. bolteae surface carbohydrates. So far, studies revealed that C. bolteae produces a specific immunogenic PS capsule comprised of disaccharide repeating blocks of mannose (Manp) and rhamnose (Rhap) units: α-D-Manp-(1→[-4)-β-D-Rhap-(1→3)-α-D-Manp-(1→]n. For vaccinology and further immunogenic experiments, a method to produce C. bolteae PS conjugates has been developed, along with the chemical syntheses of the PS non-reducing end linkage, with D-Rha or L-Rha, α-D-Manp-(1→4)-β-D-Rhap-(1→O(CH2)5NH2 and α-D-Manp-(1→4)-β-L-Rhap-(1→O(CH2)5NH2, equipped with an aminopentyl linker at the reducing end for conjugation purposes. The discovery of C. bolteae PS immunogen opens the door to the creation of non-evasive diagnostic tools to evaluate the frequency and role of this microbe in autistic subjects and to a vaccine to reduce colonization levels in the GI tract, thus impeding the concentration of neurotoxins.