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A Clinician's Primer on the Role of the Microbiome in Human Health and Disease
Abstract
The importance of the commensal microbiota that colonizes the skin, gut, and mucosal surfaces of the human body is being increasingly recognized through a rapidly expanding body of science studying the human microbiome. Although, at first glance, these discoveries may seem esoteric, the clinical implications of the microbiome in human health and disease are becoming clear. As such, it will soon be important for practicing clinicians to have an understanding of the basic concepts of the human microbiome and its relation to human health and disease. In this Concise Review, we provide a brief introduction to clinicians of the concepts underlying this burgeoning scientific field and briefly explore specific disease states for which the potential role of the human microbiome is becoming increasingly evident, including Clostridium difficile infection, inflammatory bowel disease, colonization with multidrug-resistant organisms, obesity, allergic diseases, autoimmune diseases, and neuropsychiatric illnesses, and we also discuss current and future roles of microbiome restorative therapies.
... Within an individual, microbe populations stay fairly constant over time, even though some alterations may occur with changes in lifestyle, diet and age (Guarner, et al. [5,13]). The four dominant bacterial phyla in the human gut are Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria (Khanna, et al. [14]). Most bacteria belong to the generaBacteroides, Clostridium, Faecalibacterium,Eubacterium, Ruminococcus, Peptococcus, Peptostreptococcus, and Bifidobacterium (Guarner, et al. [5,8]) . ...
... The gut-brain axis is the biochemical signalling that takes place between the gastrointestinal tract and the central nervous system (Wang, et al. [14]). That term has been expanded to include the role of the gut microbiota in the interplay; the term "microbiome-gut-brain axis" is sometimes used to describe paradigms explicitly including the gut microbiota (Wang, et al. [14,63,64]). ...
... The gut-brain axis is the biochemical signalling that takes place between the gastrointestinal tract and the central nervous system (Wang, et al. [14]). That term has been expanded to include the role of the gut microbiota in the interplay; the term "microbiome-gut-brain axis" is sometimes used to describe paradigms explicitly including the gut microbiota (Wang, et al. [14,63,64]). Broadly defined, the gut-brain axis includes the central nervous system, neuro-endocrine and neuro-immune systems including the hypothalamic-pituitary-adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system including the enteric nervous system, the vagus nerve, and the gut microbiota (Wang, et al. [14,63]). ...
... Un desequilibrio en la comunicación entre el cerebro y el sistema inmune intestinal podría contribuir a la patogenia de diversas enfermedades como la esquizofrenia, trastornos del ánimo, trastorno obsesivo-compulsivo, trastorno del espectro autista, trastorno por déficit de atención e hiperactividad, anorexia nerviosa, narcolepsia y síndrome de fatiga crónica. 13,72 En individuos genéticamente susceptibles, una microbiota intestinal alterada puede provocar una disrupción de la barrera hematoencefálica y generar autoanticuerpos contra estructuras cerebrales. 13 Si a esto se suma un estado proinflamatorio, esta disrupción en la barrera hematoencefálica puede facilitar el transporte y la unión de los autoanticuerpos a sus epítopes, lo que provocaría las enfermedades previamente mencionadas. ...
... 13 Sin embargo, no se ha estudiado si la modificación de la microbiota intestinal podría ser un tratamiento para estas enfermedades. 13,72 Autismo. La etiología exacta del autismo sigue siendo desconocida. ...
... Typically, the four dominant bacterial phyla in the human gut are Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria [30], and a standard level of diversity between these four phyla is expected in the gut of healthy individuals. However, in cases of MDD, marked alterations have been noticed in certain phyla, highlighting a potential causal relationship between MDD and microbiome composition. ...
... Clare Schrodt is a fourth year medical student at Saint Louis University who has taken part in multiple research projects including several literature reviews ranging from Reduced Firmicutes, and increased Bacteroidetes, Proteobacteria, and Actinobacteria found in rats with depression-like behavior [30]. Humans with MDD have fewer Bacteroidetes, Lachnospiraceae, Bifidobacterium, and Lactobaciillus species in their gut [28,29] and increased Alistipes [27]. ...
Background
Recent explorations into the gut microbiome of humans and animals reveal implications in chronic physical and mental health disorders. Relatively little is known regarding the relationship of gut microbiome and depression. In the current review, we reviewed existing scientific data related to the gut microbiome and healthy patients versus patients with depression. Additionally, scientific literature containing the utility of microbiome interventions to improve depression symptoms was reviewed.
Methods
A PubMed and Clinical Key literature search combined the key terms ‘gut,’ ‘microbiome,’ ‘bacteria,’ and ‘depression’ to identify studies investigating these relationships.
Results
76 relevant articles were identified. Human and animal studies reviewed examined marked alterations in the dominant bacterial phyla in the gut of individuals with depression, the connection between leaky gut and neuroinflammation in depression, brain regulatory centers impacted by changes in the gut microbiome, and the benefits of the addition of a probiotic/prebiotic for gut and mental health.
Conclusions
The current review confirmed the suspected direct communication between the gut microbiome, brain functioning, and depression. Additionally, studies suggest antibiotics disrupt the gut microbiome. There are important implications for psychiatrists in providing opportunities for intervention and enhancement of current treatments for individuals with depression.
... Thus, the commensal archaea, bacteria, fungi, protozoa, and viruses, which collectively form the human microbiome, outnumber the human cell population. Although it was largely believed that these microbes only inhabit and affect our gut, mucosal surfaces, and skin, recent research has led us to understand that our microbiomes play far larger roles in our health and well-being than previously thought (Khanna & Tosh, 2014). Disruptions of the formation and function of our microbial communities can have critical consequences for host health, including gastrointestinal disorders, allergies, obesity, and stress. ...
The average adult has over 10 trillion microorganisms located in and on their body. This staggering total is more than the number of human cells and even stars in our entire galaxy. Despite cutting-edge research revealing the critical importance of these internal ecosystems in human and planetary health, students’ understanding of the microscopic world remains limited. Syndemic, an educational video game, attempts to make this invisible world visible to users by presenting the human microbiome in an accurate, engaging way. The game takes place in the future, where a genetically engineered microbe is designed to aid the immune system in killing bacterial infections, metastasizing cancer cells, chronic allergies, and other health-related antigens. The game integrates current research through a unique collaboration with the Synthetic Biological Systems Laboratory at Columbia University. This chapter first explores our changing understanding of the microbiome and how this translated into the creation of Syndemic. We then explore the undergraduate perspective on field-testing of the game. We look at the developing arena of digital game-based learning and how both a quantitative and qualitative study of Syndemic within local and global communities fits within this framework. We show that Syndemic was an effective learning opportunity for diverse users and how it also proved a worthwhile component of undergraduate education.
... The gut microbiome is an important but "invisible organ" in humans (Khanna and Tosh, 2014). Although this "organ" is not composed of actual organs, it is distributed throughout the body, with the intestine being the primary point of distribution (Gomaa, 2020). ...
Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.
... The normal gut flora of an individual is established during early childhood or adolescence. Once established, the gut microbiota is involved in the regulation of the physiological function and innate immunity of the small intestine [101,103]. The gut microbiota also influences the proliferation and differentiation of the Lgr5 + ISCs and assists with the digestion of food [28]. ...
Over 5 000 000 adults in the world have diabetes mellitus. Diabetes mellitus like other cardiometabolic conditions is driven from the gut. More than 90% of diabetes mellitus is preceded by dysbiosis of the gut microbiota, which lead to increase in gut permeability, translocation of bacteria and their products, systemic inflammation, increased oxidative stress, mitochondria dysfunction and beta cell failure. The dysbiosis is mainly driven by lifestyle issues. Paneth cells are the main regulator of the microbiota in the gut. Failure or dysfunction of Paneth cells predisposes to dysbiosis. This article discusses theoretical basis and justification of some of the strategies which used to prevent or treat diabetes mellitus.
... The pathogenic mechanisms underlying IBS remain more or less unknown. Genetics [6,7], dietary habits [8], post-infectious conditions [9] and psychological mechanisms [10] are all suspected to be involved. In recent years an increasing number of trials have demonstrated an aberrant gut microbiota composition in IBS [11][12][13][14], although not all trials report this aberration and descriptions of it vary between studies [15]. ...
Background:
Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal disorder in developed countries and reduces patients' quality of life, hinders their ability to work, and increases health care costs. A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS, also known as 'gut dysbiosis'. Fecal microbiota transplantation (FMT) has been suggested as a treatment for IBS.
Aim:
To assess the efficacy and safety of FMT for the treatment of IBS.
Methods:
We searched Cochrane Central, MEDLINE, EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials (RCTs) investigating the effectiveness of FMT compared to placebo (including autologous FMT) in treating IBS. The primary outcome was the number of patients with improvements of symptoms measured using a validated, global IBS symptoms score. Secondary outcomes were changes in quality-of-life scores, non-serious and serious adverse events. Risk ratios (RR) and corresponding 95%CI were calculated for dichotomous outcomes, as were the mean differences (MD) and 95%CI for continuous outcomes. The Cochrane risk of bias tool was used to assess the quality of the trials. GRADE criteria were used to assess the overall quality of the evidence.
Results:
Eight RCTs (484 participants) were included in the review. FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo (RR 1.19, 95%CI: 0.68-2.10). Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group (RR 1.17, 95%CI: 0.63-2.15). One serious adverse event occurred in the FMT group and two in the placebo group (RR 0.42, 95%CI: 0.07-2.60). Endoscopic FMT delivery resulted in a significant improvement in symptoms, while capsules did not. FMT did not improve the quality of life of IBS patients but, instead, appeared to reduce it, albeit non significantly (MD -6.30, 95%CI: -13.39-0.79). The overall quality of the evidence was low due to moderate-high inconsistency, the small number of patients in the studies, and imprecision.
Conclusion:
We found insufficient evidence to support or refute the use of FMT for IBS. Larger trials are needed.
... Human microbiome research, defined as the study of the entire DNA content of microorganisms living in our bodies, has developed rapidly in recent years. As this topic has been extensively reviewed elsewhere (Cho and Blaser, 2012;Morgan et al, 2012;Kim et al, 2013;Khanna and Tosh, 2014;Lloyd-Price et al, 2016), we focus here on the available evidence demonstrating the existence of a "healthy" human blood microbiome. In addition, we investigate the potential origins and identities of "resident" microorganisms, their phylogenetic links, and the clinical significance of an allegedly healthy human blood microbiome. ...
Contributing to the city and environmental identity, buildings reflecting traditional and regional life style it has historical and aesthetic value. Structures that cause cultural, social and economic losses are faced with irreversible situations. In addition, it has caused many problems that are affected by environmental conditions and caused by design and application errors made during construction. In the first stage of the study, civil architectures in the Taraklı district of Sakarya province, which contain qualified examples of our cultural structures, were examined on site and documented with photographs. In the second stage, by examining the buildings, evaluations were made about the materials used in the buildings and the repairs they had undergone. It has been revealed that the data obtained from these
evaluations are environmental factors, physical and mechanical factors, biological factors, building physics problems and user related problems. Building physics problems (humidity, heat, sound, sun, fire and corrosion) affecting our cultural assets cause irreversible deterioration in the bearing systems of the structures and cause the destruction of historical buildings to a large extent. The aim of this study in order not to risk the transfer of our cultural assets to future generations, the current problems encountered in the selected sample area, especially the problems of building physics, have been identified. With these findings, In order to take measures specific to the structures that need to be protected, Suggestions have been made to shed light on similar negativities to be encountered in the future.
... Human microbiome research, defined as the study of the entire DNA content of microorganisms living in our bodies, has developed rapidly in recent years. As this topic has been extensively reviewed elsewhere (Cho and Blaser, 2012;Morgan et al, 2012;Kim et al, 2013;Khanna and Tosh, 2014;Lloyd-Price et al, 2016), we focus here on the available evidence demonstrating the existence of a "healthy" human blood microbiome. In addition, we investigate the potential origins and identities of "resident" microorganisms, their phylogenetic links, and the clinical significance of an allegedly healthy human blood microbiome. ...
Taraklı district of Sakarya province, which constitutes qualified examples of West Black Sea architecture, is an Ottoman settlement that has preserved its original texture by being shaped in organic texture with the effect of climatic and topographic features. The fact that it is located in the region where forest areas are dense has revealed the purpose of use of wood material. Wood is among the most preferred building materials due to it is light, easy to process and transportable. At the same time, its compatibility with nature, ease of recycling, high strength and long service life have an important place in traditional Turkish architecture.
In this study, the construction techniques and materials used in the traditional architecture of Taraklı were examined. The load bearing systems applied on wooden building walls have been classified according to the way they work under the influence of load. The load bearing systems applied on wooden building walls are classified according to the way working under the influence of load. By providing informations about foundation walls as vertical carriers
and timber framed walls, structure cover systems and structure elements have been
investigated and supported in which cases caused by deterioration was investigated and supported with photographs. The wood material used in traditional civil architecture examples forms the backbone of the structure in wooden structures. For this reason, it has been revealed that the woods of resistance to vertical and horizontal loads in the building, it is not deformation and long standing depend on the qualities that determine the value of the structure. In terms of the preservation and sustainability of the original qualities of traditional architecture, it is necessary to know the properties of the wood material to be used in the structures and to design it well.
... Human microbiome research, defined as the study of the entire DNA content of microorganisms living in our bodies, has developed rapidly in recent years. As this topic has been extensively reviewed elsewhere (Cho and Blaser, 2012;Morgan et al, 2012;Kim et al, 2013;Khanna and Tosh, 2014;Lloyd-Price et al, 2016), we focus here on the available evidence demonstrating the existence of a "healthy" human blood microbiome. In addition, we investigate the potential origins and identities of "resident" microorganisms, their phylogenetic links, and the clinical significance of an allegedly healthy human blood microbiome. ...
In certain areas of animal research summarizations of literature data are needed,
statistical methods dealing for the analysis of summary data from the literature are known as meta-analysis. The method of meta-analysis is used to combine the result from several independent studies which have been done in different regions or areas on a specific subjectas qualitative and quantitative and assist to achieve a consensus. The current meta-analysis was performed to provide the association between prolactin PRL polymorphism with some productive milk traits in Holstein crossbreed dairy cattle. The data was collected from the years 2002 to 2021 and a total of 26 published studies were included in milk yield study, 14 studies for protein yield, and 18 studies included for protein content. For the performance of
statistical evaluation four genetic models, dominant; AA + AB versus BB, recessive; AA versus AB + BB, co-dominant; AA versus BB versus AB were employed to obtain
standardized mean difference (SMD) between genotypes. In this analysis cattle with AB versus BB genotype (SMD= 0.289, 95% CI 0.005, 0.573) and a statistically significant (p<0.05) higher protein yield were found compared to AA versus AB and AA versus BB genotype. In the remaining cases, the association between prolactin polymorphism and milk yield and protein content was not statistically significant (p>0.05).
Keywords: Meta-analysis, crossbreed, Polymorphism, co-dominant, PRL, SMD.
... Human microbiome research, defined as the study of the entire DNA content of microorganisms living in our bodies, has developed rapidly in recent years. As this topic has been extensively reviewed elsewhere (Cho and Blaser, 2012;Morgan et al, 2012;Kim et al, 2013;Khanna and Tosh, 2014;Lloyd-Price et al, 2016), we focus here on the available evidence demonstrating the existence of a "healthy" human blood microbiome. In addition, we investigate the potential origins and identities of "resident" microorganisms, their phylogenetic links, and the clinical significance of an allegedly healthy human blood microbiome. ...
Meta-Analysis is defined as the collection of analyses or top analysis when it is
considered as the meaning of the word. Meta-analysis is a statistical analysis method in which
the results of many independent studies conducted on a specific topic are evaluated together.
This study aims to investigate the relationship of Kappa-Casein (CSN3) gene polymorphism
with lactation milk yield, fat yield, and protein yield in Holstein breed cattle. For this purpose,
the Meta-Analysis method was used. All databases reached for the study were searched by
using appropriate keywords to cover the years 2002-2022, taking into account all national and
international studies. Data were obtained by examining 15 studies for lactation milk yield, 10
studies for fat yield, and 9 studies for protein yield that meets the research criteria. Statistical
analyses were performed using the Stata 11.2 software program. Codominant (AB versus AA,
BB versus AA, and BB versus AB), dominant (AA+AB - BB), and recessive (AB+BB versus
AA) were used as inheritance models. As a result of the study, the relationship between CSN3
gene polymorphism and lactation milk yield and protein yield was found to be insignificant
(p>0.05), while the relationship between CSN3 gene polymorphism and fat yield (AA versus
AB and AB versus BB) was significant (respectively p<0.05 and p<0.01).
Keywords: Kappa-Casein, Meta-Analysis, Polymorphism, Holstein
... Proteobacteria is a major bacterial phylum associated with IBD in the gut microbiota 22 , and many pathogens belong to Proteobacteria, such as Brucella, Bordetella, Neisseria, Yersinia, Salmonella, Escherichia, and Helicobacter. Several studies have reported that an abnormal expansion of Proteobacteria is one of the characteristics of dysbiosis 26,27 , and the dysregulated host-microbiota interactions cause gut microbiota-related diseases, including IBD 13,25,64 . ...
Axl is a tyrosine kinase receptor, a negative regulator for innate immune responses and inflammatory bowel disease (IBD). The gut microbiota regulates intestinal immune homeostasis, but the role of Axl in the pathogenesis of IBD through the regulation of gut microbiota composition remains unresolved. In this study, mice with DSS-induced colitis showed increased Axl expression, which was almost entirely suppressed by depleting the gut microbiota with antibiotics. Axl−/− mice without DSS administration exhibited increased bacterial loads, especially the Proteobacteria abundant in patients with IBD, significantly consistent with DSS-induced colitis mice. Axl−/− mice also had an inflammatory intestinal microenvironment with reduced antimicrobial peptides and overexpression of inflammatory cytokines. The onset of DSS-induced colitis occurred faster with an abnormal expansion of Proteobacteria in Axl−/− mice than in WT mice. These findings suggest that a lack of Axl signaling exacerbates colitis by inducing aberrant compositions of the gut microbiota in conjunction with an inflammatory gut microenvironment. In conclusion, the data demonstrated that Axl signaling could ameliorate the pathogenesis of colitis by preventing dysbiosis of gut microbiota. Therefore, Axl may act as a potential novel biomarker for IBD and can be a potential candidate for the prophylactic or therapeutic target of diverse microbiota dysbiosis-related diseases.
... However, whether gut microbiota influences MM remains to be explored. The human gut microbiota is comprised of trillions of bacteria and other microorganisms that live on and inside humans [4], most of which belong to the phyla of Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria [5]. The composition of the gut microbiota is shaped by several factors (including host genetics, colonization at the time of birth, type of birth delivery, lifestyle, and exposure to antibiotics [6-8]), which remains relatively constant throughout adult life except for the influence of diet, change of lifestyle, diseases, and corresponding treatment [9]. ...
Although novel therapies have dramatically improved outcomes for multiple myeloma (MM) patients, relapse is inevitable and overall outcomes are heterogeneous. The gut microbiota is becoming increasingly recognized for its influence on host metabolism. To date, evidence has suggested that the gut microbiota contributes to MM, not only via the progressive activities of specific bacteria but also through the influence of the microbiota on host metabolism. Importantly, the abnormal amino acid metabolism, as well as the altered microbiome in MM, is becoming increasingly apparent, as is the influence on MM progression and the therapeutic response. Moreover, the gut-microbiota–host-amino-acid metabolism interaction in the progression of MM has been highlighted. Modulation of the gut microbiota (such as fecal microbiota transplantation, FMT) can be modified, representing a new angle in MM treatment that can improve outcomes. In this review, the relationship between gut microbiota, metabolism, and MM, together with strategies to modulate the microbiota, will be discussed, and some unanswered questions for ongoing and future research will be presented.
... Microbial population residing in the guts generally known as intestinal flora is now described as microbiome or microbiota. 1 Bacteria, viruses, fungi and parasites are all part of this complex ecosystem, having different biological role while interacting with each other in the process of food digestion hence affecting the health conditions of the individual host. Among all microorganisms, the role of bacteria in food digestion and its processing is prevalent. ...
Female patient, 68-years-old, suffering for 42 years from irritable bowel syndrome (IBS) reached to my attention in social media during summer 2020 by complaining miserable experience devastating her life quality. Patient has been resided in Salt lake City, UT for the past 23 years and has been examined by numerous physicians throughout the years. She has been under medication and severe dietary program. She consumed daily dosages of digestive enzyme complex (Holoenzyme™) and Probiotic 10 capsules (Nature’s Bounty™). She had been restricted in consumption of fruits, vegetables, dairy products either cooked or raw. She suffered severe stomachache, bloating and crumpling for hours to come after consuming incompatible food ingredients. The patient communicating only by means of text messages was advised to stop the current medication and consume fermented milk beverages in order to provide sufficient supply of live probiotics. Within a day or two, she started to send complements by experiencing joy and surprise after ingesting fermented milk beverage known as Kefir manufactured by Lifeway™. No pain whatsoever, while being able to ingest various foods and fresh organics. According to the recent communications, it is assumed that patient was diagnosed skeptically and ill-advised by previous practitioners for many years hence devastating her quality of life. Regardless of assigning IBS or confirming any other clinical symptom, the patient simply was suffering from simple physiological disorder caused by incompatible microbial activity in her guts.
... Human microbiome research, defined as the study of the entire DNA content of microorganisms living in our bodies, has developed rapidly in recent years. As this topic has been extensively reviewed elsewhere (Cho and Blaser, 2012;Morgan et al, 2012;Kim et al, 2013;Khanna and Tosh, 2014;Lloyd-Price et al, 2016), we focus here on the available evidence demonstrating the existence of a "healthy" human blood microbiome. In addition, we investigate the potential origins and identities of "resident" microorganisms, their phylogenetic links, and the clinical significance of an allegedly healthy human blood microbiome. ...
ABSTRACT
Inductively coupled plasma-mass spectroscopy, known as ICP-MS, is a spectroscopic device that analyzes many elements in the dream table, such as trace elements, minerals and heavy metals, which are basic inorganic things, with high selectivity and sensitivity. Materials collected from living things such as humans, animals, plants, fungi, bacteria, and model organisms constitute biological sample groups. These materials include; body fluids, tissue, cells and many other components. Researchers need specific types of biological samples to perform their work and advance medicine. The analysis of elements in biological samples is very important in terms of clinical and routine analysis. Apart from this, studies that have contributed to the literature in recent years have been carried out as a research and examination subject. The reason why ICP-MS is highly preferred in biological samples is that it has the ability to quickly measure many elements simultaneously, at very low detection limits. Although ICP-MS is highly preferred in biological samples, various difficulties arise in its use. These are low concentrations of the target species in a small amount of samples, matrix effect, contamination and various interferences. The most common is the contamination that may occur during sampling and storage. The materials used in the sample collection stage should be carefully selected to avoid elemental contamination and should be plastic. Plastic materials used in sample preparation and collection should be washed with 2% nitric acid. Samples can be stored for a long time at +4-8 °C with pre-treatment, convert to solution and acidification processes. Apart from this, in order to analyze biological samples with ICP MS, it is necessary to convert the samples into liquid form and remove the majority of their organic components. Biological samples cause matrix effect due to their organic components and high salt content. Digestion of the organic part, dilution up to a certain rate, is effective in reducing matrix interactions. In this sense, sample preparation is the first and most important step in ICP-MS analysis. For this purpose, microwave combustion systems are mostly used in sample preparation. Analyzing the sample by applying the sample directly to the device in ICP-MS devices produced in different designs provides a great advantage in biological samples. ICP-MS, which is highly preferred in routine clinical analyzes and toxicology, is a powerful and analytical device with its high sensitivity and ability to quickly analyze many elements at the same time. In recent years, research with the ICP-MS device has gained momentum in many diseases and pathological conditions.
... Microbial communities are ubiquitously present in many environmental niches on earth, including soil (1), water (2) and air (3). They are a critical component of the human system, playing important roles in maintaining human health and wellbeing (4)(5)(6). Human microbiome dysbiosis can lead to various diseases, such as obesity (7)(8)(9)(10), diabetes (11,12) and inflammatory bowel disease (13)(14)(15). On the other hand, human microbiome intervention has recently been explored as a meaningful non-invasive treatment. ...
Metagenomics is the study of all genomic content contained in given microbial communities. Metagenomic functional analysis aims to quantify protein families and reconstruct metabolic pathways from the metagenome. It plays a central role in understanding the interaction between the microbial community and its host or environment. De novo functional analysis, which allows the discovery of novel protein families, remains challenging for high-complexity communities. There are currently three main approaches for recovering novel genes or proteins: de novo nucleotide assembly, gene calling and peptide assembly. Unfortunately, their information dependency has been overlooked, and each has been formulated as an independent problem. In this work, we develop a sophisticated workflow called integrated Metagenomic Protein Predictor (iMPP), which leverages the information dependencies for better de novo functional analysis. iMPP contains three novel modules: a hybrid assembly graph generation module, a graph-based gene calling module, and a peptide assembly-based refinement module. iMPP significantly improved the existing gene calling sensitivity on unassembled metagenomic reads, achieving a 92–97% recall rate at a high precision level (>85%). iMPP further allowed for more sensitive and accurate peptide assembly, recovering more reference proteins and delivering more hypothetical protein sequences. The high performance of iMPP can provide a more comprehensive and unbiased view of the microbial communities under investigation. iMPP is freely available from https://github.com/Sirisha-t/iMPP.
... The most commonly detected phyla in AUS in the present study were Proteobacteria, Firmicutes, Actinobacteriota, and Actinobacteria. The Proteobacteria, Firmicutes, and Actinobacteria are also three of the four predominant gut microbiota phyla [52]. The possibility that, and mechanism by which, gut flora gain access to indwelling AUS devices warrants investigation. ...
The artificial urinary sphincter (AUS) is an effective treatment option for incontinence due to intrinsic sphincteric deficiency in the context of neurogenic lower urinary tract dysfunction, or stress urinary incontinence following radical prostatectomy. A subset of AUS devices develops infection and requires explant. We sought to characterize biofilm composition of the AUS device to inform prevention and treatment strategies. Indwelling AUS devices were swabbed for biofilm at surgical removal or revision. Samples and controls were subjected to next-generation sequencing and metabolomics. Biofilm formation of microbial strains isolated from AUS devices was reconstituted in a bioreactor mimicking subcutaneous tissue with a medical device present. Mean patient age was 73 (SD 10.2). All eighteen artificial urinary sphincter devices harbored microbial biofilms. Central genera in the overall microbe–metabolite interaction network were Staphylococcus (2620 metabolites), Escherichia/Shigella (2101), and Methylobacterium-Methylorubrum (674). An rpoB mutation associated with rifampin resistance was detected in 8 of 15 (53%) biofilms. Staphylococcus warneri formed greater biofilm on polyurethane than on any other material type (p < 0.01). The results of this investigation, wherein we comprehensively characterized the composition of AUS device biofilms, provide the framework for future identification and rational development of inhibitors and preventive strategies against device-associated infection.
... To the best of our knowledge, no previous studies have investigated the possible similarities in the gut microbiota profile of patients with CD, NCWS, and IBS compared to healthy control. Hence, we designed this monocentric prospective observational study to compare the relative abundance of Firmicutes and Bacteroidetes, as the two most dominant phyla [35][36][37][38], and Bifidobacterium and Lactobacillus, as two highly controversial genera of fecal microbial communities, among Iranian subjects with CD, NCWS, and IBS compared to HCs. ...
Background and aims
Individuals with celiac disease (CD), non-celiac wheat sensitivity (NCWS), and irritable bowel syndrome (IBS), show overlapping clinical symptoms and experience gut dysbiosis. A limited number of studies so far compared the gut microbiota among these intestinal conditions. This study aimed to investigate the similarities in the gut microbiota among patients with CD, NCWS, and IBS in comparison to healthy controls (HC).
Materials and methods
In this prospective study, in total 72 adult subjects, including CD (n = 15), NCWS (n = 12), IBS (n = 30), and HC (n = 15) were recruited. Fecal samples were collected from each individual. A quantitative real-time PCR (qPCR) test using 16S ribosomal RNA was conducted on stool samples to assess the relative abundance of Firmicutes , Bacteroidetes , Bifidobacterium spp., and Lactobacillus spp.
Results
In all groups , Firmicutes and Lactobacillus spp. had the highest and lowest relative abundance respectively. The phylum Firmicutes had a higher relative abundance in CD patients than other groups. On the other hand, the phylum Bacteroidetes had the highest relative abundance among healthy subjects but the lowest in patients with NCWS . The relative abundance of Bifidobacterium spp. was lower in subjects with CD ( P = 0.035) and IBS ( P = 0.001) compared to the HCs. Also, the alteration of Firmicutes to Bacteroidetes ratio (F/B ratio) was statistically significant in NCWS and CD patients compared to the HCs ( P = 0.05).
Conclusion
The principal coordinate analysis (PCoA), as a powerful multivariate analysis, suggested that the investigated gut microbial profile of patients with IBS and NCWS share more similarities to the HCs. In contrast, patients with CD had the most dissimilarity compared to the other groups in the context of the studied gut microbiota.
... In contrast, as people age, the diversity of the microbiota declines [39]. The gut microbiome bacterial core is dominated by 4 major phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria [40]. In neonatal mice, Proteobacteria is the dominant phylum: during this stage of life, Proteobacteria-specific IgA maintains the relative bacterial population and controls microbiota maturation [41,42]. ...
Human body is colonized by a florid microbial community of bacteria, archaea, fungi, protists, helminths, and viruses, known as microbiota, which co-evolves with the host and influences its health through all stages of its life. It is well known that oral microorganisms form highly structurally and functionally organized multi-species biofilms and establish a network of complex mutual inter-species interactions having a primary function in synergy, signaling, or antagonism. This ecological model allows the microorganisms to increase their resistance to antimicrobial agents and settle a balanced microbes-host symbiotic relationship that ensures oral and global health status in humans. The host-associated microbiome is an important factor in human health and disease. Therefore, to develop novel diagnostic, therapeutic, and preventive strategies, microbiome’s functions and the reciprocal interactions every microbiome entertains with other microbial communities in the human body are being investigated. This review provides an analysis of the literature about the close connection between the two largest microbial communities in humans: the oral and the gut microbiomes. Furthermore, it focuses on how the alteration of their microbial and functional characteristics can lead to and reciprocally influence the onset of both oral and intestinal microbiome-associated illness, along with the potential role of probiotics in ameliorating inflammation and microbial dysbiosis.
... Antibiotic usage can disrupt the ability of gut micobiota to inhibit pathogen growth, due to the reduction of native bacterial species, therefore causing antibiotic diarrhea [9]. Antibiotic usage may also enhance horizontal AMR gene transfer from commensal bacteria to pathogens in gut microbiota, through which antibiotic resistant pathogens that are difficult to treat with common antibiotics are created [10,11]. Probiotics are microorganisms that are beneficial to health when supplemented as part of the human diet [12]. ...
Antibiotic usage and yogurt consumption are the major interventions for gut microbiota, yet their shared characteristics and disparities in healthy human gut microbiome remain unclear. This study aimed to decipher the composition changes among healthy humans, comparing antibiotic usage and yogurt consumption. The relative bacterial abundances of 1113 fecal samples were collected from an ongoing, population-based longitudinal cohort study in China that covered lifestyle, diet, disease status and physical measurements, and biological indicators of participants were obtained by the sequencing of 16S rRNA. The samples were divided into three groups, which were antibiotic users (122), yogurt consumers (497) and controls (494), where data visualization, alpha diversity, beta diversity and LEfSe analysis were conducted. At the family level, the relative abundances of Streptococcaceae, Enterobacteriaceae and Enterococcaceae families in antibiotic users increased almost 50%, 70% and 200%, respectively, while yogurt consumption also increased relative abundances of Streptococcaceae and Enterococcaceae, but not Enterobacteriaceae. Alpha diversity analyses suggested that the microbiome of the antibiotic usage and yogurt consumption groups exhibited an alpha diversity lower than that of the control. LEfSe analysis showed that, at the family level, the number of biomarkers in the yogurt consumption and antibiotic usage group were respectively 5 and 7, lower than that of the control (13). This study demonstrated the importance in considering the potential assistance of yogurt consumption on ARG gene transfer from commensal bacteria to pathogens in the human gut, which may pose a risk for human health. Antibiotic usage and yogurt consumption share more identical changes on healthy human gut flora than disparities. Therefore, in order to understand the potential risks of antibiotic usage and yogurt consumption on antibiotic resistance transmission in human gut microbiota, further research needs to be undertaken.
... Early evidence from mouse models favored a role for microbes in MM development. The most abundant components of the human intestinal microbiota are bacteria that mainly belong to four phyla, namely Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria (41), and the role of gut microbes in humans is usually studied using metagenomic sequencing or 16S ribosomal RNA (rRNA) sequencing. The MM microbiota exhibits compositional alterations (usually termed microbiota dysbiosis) compared with the gut microbiota of healthy individuals, reflecting a different ecological microenvironment in MM patients (19,42). ...
The gut commensal microbes modulate human immunity and metabolism through the production of a large number of metabolites, which act as signaling molecules and substrates of metabolic reactions in a diverse range of biological processes. There is a growing appreciation for the importance of immunometabolic mechanisms of the host-gut microbiota interactions in various malignant tumors. Emerging studies have suggested intestinal microbiota contributes to the progression of multiple myeloma. In this review, we summarized the current understanding of the gut microbiome in MM progression and treatment, and the influence of alterations in gut microbiota on treatment response and treatment-related toxicity and complications in MM patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, we discussed the impact of gut microbiota-immune system interactions in tumor immunotherapy, focusing on tumor vaccine immunotherapy, which may be an effective approach to improve anti-myeloma efficacy.
... Сообщество микроорганизмов, обитающее в желудочно-кишечном тракте (ЖКТ) человека и животных, составляет микробиоту кишечника [123]. Это около 100 трлн клеток, что почти в 10 раз больше, чем количество клеток организма человека [124], при этом совокупный геном микроорганизмов (микробиом) превышает геном человека в 100 раз [125]. Бактериальный геном может кодировать свыше 5000 полипептидов и белков и обладает большими метаболическими возможностями [126]. ...
The review discusses the complex role of the intestinal microbiota in the pathogenesis of multiple sclerosis, summarizes data from studies of changes in the composition of the intestinal microbiome in patients with multiple sclerosis, and provides evidence of the involvement of the intestinal microbiota in the development of experimental autoimmune encephalomyelitis in animals, a valid model of multiple sclerosis.
... The population of Proteobacteria, a major phylum of Gram-negative bacteria, and Actinobacteria, a phylum of Gram-positive bacteria, typically constitute the remaining proportion of bacterial organisms in the gut microbiota (Khanna and Tosh, 2014). Actinobacteria, specifically Frontiers in Neuroscience 06 frontiersin.org ...
Several studies investigating the pathogenesis of Alzheimer’s disease have identified various interdependent constituents contributing to the exacerbation of the disease, including Aβ plaque formation, tau protein hyperphosphorylation, neurofibrillary tangle accumulation, glial inflammation, and the eventual loss of proper neural plasticity. Recently, using various models and human patients, another key factor has been established as an influential determinant in brain homeostasis: the gut–brain axis. The implications of a rapidly aging population and the absence of a definitive cure for Alzheimer’s disease have prompted a search for non-pharmaceutical tools, of which gut-modulatory therapies targeting the gut–brain axis have shown promise. Yet multiple recent studies examining changes in human gut flora in response to various probiotics and environmental factors are limited and difficult to generalize; whether the state of the gut microbiota in Alzheimer’s disease is a cause of the disease, a result of the disease, or both through numerous feedback loops in the gut–brain axis, remains unclear. However, preliminary findings of longitudinal studies conducted over the past decades have highlighted dietary interventions, especially Mediterranean diets, as preventative measures for Alzheimer’s disease by reversing neuroinflammation, modifying the intestinal and blood–brain barrier (BBB), and addressing gut dysbiosis. Conversely, the consumption of Western diets intensifies the progression of Alzheimer’s disease through genetic alterations, impaired barrier function, and chronic inflammation. This review aims to support the growing body of experimental and clinical data highlighting specific probiotic strains and particular dietary components in preventing Alzheimer’s disease via the gut–brain axis.
... Microbiota analyses indicated that Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the dominant phyla in the human feces (Fig. 5A). Firmicutes and Bacteroidetes account for (83.5 ± 9.8) % of the total gut microbiota, which is concordant with previous studies (Khanna and Tosh, 2014;Shreiner et al., 2015;Arumugam et al., 2011;Hooper and Gordon, 2001). Proteobacteria and Bacteroidetes were the main phyla in environmental samples, with Proteobacteria accounting for the highest percentage (50.6 ± 23.9 %). ...
Discharged wastewater treatment plant (WWTP) effluents can contaminate receiving water bodies with human feces and alter the abundance of antibiotic resistance genes (ARGs). In this study, we examined the co-occurrence of ARGs, human fecal pollution indicator crAssphage, and antibiotics in human feces and a series of connected receiving water bodies affected by human feces, including water from different treatment units of a WWTP, river, lake, and tap waters. Results showed that crAssphage was detected in 68.2% of the studied water bodies, confirming widespread human fecal contamination. Both ARG and crAssphage abundances exhibited a distance-decay effect from the emission source to the receiving environment. Interestingly, the detected ARG abundance in the water bodies was significantly correlated with crAssphage abundance but not with the residual antibiotic concentration, demonstrating that the presence of ARG could largely be explained by the extent of fecal pollution, with no clear signs of antibiotic selection. In addition, 14 ARGs co-shared by human feces and water bodies were significantly correlated with crAssphage. Furthermore, a close evolutionary relationship was observed between the blaTEM-1 gene from human feces and aquatic environments. These results imply a potential ARG exchange between human feces and receiving water bodies. Overall, this study provides important insights into the distribution and sources of ARGs in water bodies affected by human fecal contamination.
... Followed by α-Proteobacteria which showed a 40-50 times fold increase in expression of bacterial DNA than the untreated controls. In the human context, these 4 major phyla have been extensively studied (Khanna and Tosh 2014). Of them, during inflammatory conditions such as IBD (Crohn's disease and ulcerative colitis), Proteobacteria has been shown to drastically increase in mammalian models and humans (Shin et al. 2015;Sartor 2008;Rehman et al. 2010;Gophna et al. 2006). ...
Inflammatory bowel disease (IBD) is a group of disorders characterized by chronic inflammation in the intestine. Several studies confirmed that oxidative stress induced by an enormous amount of reactive free radicals triggers the onset of IBD. Currently, there is an increasing trend in the global incidence of IBD and it is coupled with a lack of adequate long-term therapeutic options. At the same time, progress in research to understand the pathogenesis of IBD has been hampered due to the absence of adequate animal models. Currently, the toxic chemical Dextran Sulfate Sodium (DSS) induced gut inflammation in rodents is widely perceived as a good model of experimental colitis or IBD. Drosophila melanogaster, a genetic animal model, shares ~ 75% sequence similarity to genes causing different diseases in humans and also has conserved digestion and absorption features. Therefore, in the current study, we used Drosophila as a model system to induce and investigate DSS-induced colitis. Anatomical, biochemical, and molecular analyses were performed to measure the levels of inflammation and cellular disturbances in the gastrointestinal (GI) tract of Drosophila. Our study shows that DSS-induced inflammation lowers the levels of antioxidant molecules, affects the life span, reduces physiological activity and induces cellular damage in the GI tract mimicking pathophysiological features of IBD in Drosophila. Such a DSS-induced Drosophila colitis model can be further used for understanding the molecular pathology of IBD and screening novel drugs.
Supplementary information:
The online version contains supplementary material available at 10.1007/s13205-022-03349-2.
... The vaginal microbiota Studies report that the human body hosts around 4 × 10 13 bacteria, encompassing thousands of different bacterial species, with each site of the body having its own unique complement of microorganisms and communities: its microbiota (20). The human microbiome has been shown to play an important role in health and disease (21,22). Much of our knowledge of the FRT microbiota relates to the vaginal microbiota, the native bacteria found lining the vaginal epithelial cells that exists in a symbiotic relationship with its host. ...
The intricate interactions between the host cells, bacteria, and immune components that reside in the female reproductive tract (FRT) are essential in maintaining reproductive tract homeostasis. Much of our current knowledge surrounding the FRT microbiota relates to the vaginal microbiota, where ‘health’ has long been associated with low bacterial diversity and Lactobacillus dominance. This concept has recently been challenged as women can have a diverse vaginal microbial composition in the absence of symptomatic disease. The structures of the upper FRT (the endocervix, uterus, Fallopian tubes, and ovaries) have distinct, lower biomass microbiotas than the vagina; however, the existence of permanent microbiotas at these sites is disputed. During homeostasis, a balance exists between the FRT bacteria and the immune system that maintains immune quiescence. Alterations in the bacteria, immune system, or local environment may result in perturbances to the FRT microbiota, defined as dysbiosis. The inflammatory signature of a perturbed or “dysbiotic” FRT microbiota is characterized by elevated concentrations of pro-inflammatory cytokines in cervical and vaginal fluid. It appears that vaginal homeostasis can be disrupted by two different mechanisms: first, a shift toward increased bacterial diversity can trigger vaginal inflammation, and second, local immunity is altered in some manner, which disrupts the microbiota in response to an environmental change. FRT dysbiosis can have negative effects on reproductive health. This review will examine the increasing evidence for the involvement of the FRT microbiotas and inflammation in gynecologic conditions such as endometriosis, infertility, and endometrial and ovarian cancer; however, the precise mechanisms by which bacteria are involved in these conditions remains speculative at present. While only in their infancy, the use of antibiotics and probiotics to therapeutically alter the FRT microbiota is being studied and is discussed herein. Our current understanding of the intimate relationship between immunity and the FRT microbiota is in its early days, and more research is needed to deepen our mechanistic understanding of this relationship and to assess how our present knowledge can be harnessed to assist in diagnosis and treatment of gynecologic conditions.
... Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria have been recognized as the four dominant bacterial phyla. [31] Some studies have reported Firmicutes and Bacteroidetes to be the dominant phyla, [32][33][34] while our study, found Firmicutes, followed by Actinobacteria and Bacteroidetes to be dominant. These variations can be explained by ethnicity, genetics, diet, and lifestyles. ...
Background:
The main composition of intestinal microbiota in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients has not yet been elucidated. In this, case-control study, we identified differences of intestinal microbiota in male patients with NAFLD, presumed NASH, and healthy controls.
Materials and methods:
We compared gut microbial composition of 25 patients with NAFLD, 13 patients with presumed NASH, and 12 healthy controls. Demographic information as well as clinical, nutritional, and physical activity data was gathered. Stool and blood samples were collected to perform the laboratory analysis. The taxonomic composition of gut microbiota was assessed using V4 regions of microbial small subunit ribosomal Ribonucleic acid genes sequencing of stool samples.
Results:
Firmicutes, Actinobacteria, and Bacteroidetes were the most frequently phyla in all groups. Our results revealed that Veillonella was the only genus with significantly different amounts in presumed NASH patients compared with patients with NAFLD (P = 2.76 × 10-6, q = 2.07 × 10-4, logFC = 5.52).
Conclusion:
This pilot study was the first study to compare gut microbial composition in patients with NAFLD and presumed NASH in the Middle East. Given the potential effects of gut microbiota on the management and prevention of NAFLD, larger, prospective studies are recommended to confirm this study's findings.
... The oral cavity is the window of the body, and it is home to a diverse microbial community encompassing one of the most complex microbiomes and dynamic microbial communities, comprising hundreds of different species of bacteria living in a structure known as a biofilm. Dysbiosis of the periodontal microbiota can interfere with the normal function of the host immune system, resulting in the development of inflammatory diseases, such as periodontal disease [1][2][3]. Periodontitis is an infectious and inflammatory disorder that is characterized by the destruction of the supporting structure of teeth, induced by biofilm dysbiosis, in which a higher proportion of major pathogens such as red complex species, including Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola, and a low proportion of beneficial strains, such as Actinomyces sp. or Streptococcus sp., remain the key to microbial disruption [3][4][5]. Despite improvements in preventive measures over the past 40 years, periodontal disease continues to contribute to widespread oral health ...
(1) Background: Probiotics can be considered a non-invasive periodontal monotherapy for the modulation of microbiota when periodontal treatment is not accessible. The aim was to evaluate the ability of Lactobacillus reuteri Prodentis as monotherapy to modulate periodontal parameters and subgingival biofilm dysbiosis. (2) Methods: A 30-year-old patient with periodontitis was followed longitudinally after one month of daily consumption of L. reuteri Prodentis (T0). Periodontal measurements and microbial identification by Checkerboard DNA–DNA hybridization of 40 bacteria were compared between baseline (T0) and 30 days (T1) or 90 days (T2), using the Kruskal–Wallis (KW) and Mann–Whitney U (MW) tests. (3) Results: Low values of pocket depth, attachment level, dental plaque, gingival erythema (GE), and suppuration were observed at T0 vs. T1, with the clinical improvement of GE (p < 0.05, MW) and the recovery of tooth 46 fistulation. T1 vs. T0 comparisons showed lower levels (Lev) or proportions (Prop) of Parvimonas micra (Lev: p < 0.05, MW; Prop: p < 0.01, MW) and Streptococcus gordonii (Prop: p < 0.05, MW), and a predominance (Lev/Prop) of Actinomyces odontolyticus and Streptococcus mitis; lower levels and proportions of P. micra, Eubacterium saburreum, Porphyromonas gingivalis, and Tannerella forsythia were observed in tooth 46 (T1/T2 vs. T0). (4) Conclusions: Under monotherapy with L. reuteri Prodentis, periodontal measurements of the patient were maintained, with selective changes in the subgingival microbiota that were proportional to the time of probiotic administration, with any additional periodontal treatment.
... In other studies, at the phylum level in obese; while an increase in the Firmicutes level was observed, a decrease in Bacteroidetes was reported, and the situation was reversed in people who were thin and dieted. [4,7,11,30]. Firmicutes / Bacteroidetes ratio was higher in females with increased body mass index compared to males [11] and an increase in Firmicutes / Bacteroidetes ratio showed that the person was a candidate for obesity. ...
The aim of our study is to examine the effect of thymoquinone (TQ) in obese rats induced with an antipsychotic drug olanzapine (OL). Thirty-five female Spraque-Dawley rats were divided into five groups (n = 7): Control, OL (2 mg / kg OL daily), OL + TQ1 (2 mg / kg OL + 20 mg / kg TQ), OL + TQ2 (2 mg / kg OL + 40 mg / kg TQ) and the OL + TQ3 group (2 mg / kg OL + 80 mg / kg TQ). On the 15th day of treatment, intestinal tissue was removed for analysis. It has been found that TQ treatment affects the levels of Firmicutes and Bacteroides at varying rates in the intestinal flora in OL + TQ1, OL + TQ2 and OL + TQ3 groups, and also has a significant role in the apoptotic effect of TQ. In conclusion, with this study, it was determined that the treatment of TQ has a protective property against the side effects of OL. TQ can be an effective treatment method to increase therapeutic effectiveness.
... The terms microbiome and microbiota are used to describe all microorganisms that live in populations of microorganisms in different ecosystems of the body of all microorganisms. [16] As the most common types of bacteria, bacteroids, actin bacteria, and proteobacteria can be given as examples. The physiological primary role of the microbiota is to strengthen the metabolic and immune systems and provide intestinal motility. ...
Gluten is a herbal protein found in grains such as wheat, rye, and barley. Casein is an animal protein found in cows, goats, sheep, and human milk. Since it is not digested properly in people suffering from intestinal-based psychological disorders, its chemical properties turn into structures similar to morphine. Gluten and casein peptides such as gluteomorphin and casomorphine were found in urine samples taken from patients with diseases like Down syndrome, schizophrenia, depression, autism, and epilepsy. These peptides cross the vascular structure through the blood to the brain and the fluid in the brain, causing the function of some areas of the brain to be slowed down. This condition, which originates in the digestive system, is more frequent in people who have an intestine-based psychiatric disease. The psychiatric effects of gluten and casein on different individuals were examined in this review based on the research in the literature, and it was revealed that the findings of these effects were not the same in everyone. Although a gluten-free, casein-free diet is not a cure-all, it can help lessen psychological symptoms.
... [25] Studies have shown that changes to the composition of the gut microbiota have been linked to many diseases and conditions such as clostridium difficile infection, [26] inflammatory bowel disease, [3] colorectal cancer [1,2] (CRC), and human immunodeficiency virus infection. [27] The four predominant phyla in the gut are Firmicutes, Bacteriodetes, Actinobacteria, and Proteobacteria, [28] together they constitute more than 95% of the gut microbiome. Previous studies have shown that higher proportions of Firmicutes and lower proportions of Actinobacteria are commonly observed in CRC patients compared to the gut microbiome of healthy subjects. ...
During the past decade, breakthroughs in sequencing technology have provided the basis for studies of the myriad ways in which microbial communities in and on the human body influence human health and disease. In almost every medical specialty, there is now a growing interest in accurate and quantitative profiling of the microbiota for use in diagnostic and therapeutic applications. However, the current next‐generation sequencing approach for microbiome profiling is costly, requires laborious library preparation, and is challenging to scale up for routine diagnostics. Split, Amplify, and Melt analysis of BActeria‐community (SAMBA), a novel multicolor digital melting polymerase chain reaction platform with unprecedented multiplexing capability is presented, and the capability to distinguish and quantify 16 bacteria species in mixtures is demonstrated. Subsequently, SAMBA is applied to measure the compositions of bacteria in the gut microbiome to identify microbial dysbiosis related to colorectal cancer. This rapid, low cost, and high‐throughput approach will enable the implementation of microbiome diagnostics in clinical laboratories and routine medical practice. The Split, Amplify, and Melt analysis of BActeria‐community (SAMBA) assay performs single‐molecule identification of 16S rDNA from complex mixtures in a rapid, high‐throughput platform. SAMBA exploits melt‐curve analysis of multicolor molecular beacon probes across ≈37 000 partitions in a microfluidic chip to perform quantitative polymicrobial profiling, and is capable of detecting microbiome dysbiosis associated with colorectal cancer from fecal samples.
... The gut contains approximately 500-1000 different microorganisms. 12 The gut microbiota in germ-free mice plays an important role in regulating energy harvest and storage, as well as weight gain and fat composition. 13 Probiotics are live microorganisms (including Bifidobacterium and Lactobacillus) that confer multiple health benefits. ...
Background and hypothesis:
Antipsychotic-induced weight gain is associated with alterations to the composition of the gut microbiota. The purpose of this study was to determine the effect of probiotics plus dietary fiber on antipsychotic-induced weight gain.
Study design:
Two sequential, randomized clinical trials were conducted. In Study 1, 90 drug-naïve, first-episode schizophrenia patients were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy for 12 weeks. In Study 2, 60 drug-naïve, first-episode schizophrenia patients were randomly assigned to receive either olanzapine plus probiotics and dietary fiber or olanzapine monotherapy for 12 weeks.
Study results:
In Study 1, no significant differences in weight gain were observed between the two groups. The insulin resistance index (IRI) was lower in the olanzapine plus probiotics group compared with the olanzapine monotherapy group at week 12 (estimated mean difference, -0.65, [95% confidence interval (CI), -1.10 to -0.20]; p = .005). In Study 2, weight gain was lower in the probiotics plus dietary fiber group than in the olanzapine monotherapy group at week 12 (estimated mean difference -3.45 kg, [95% CI, -5.91 to -1.00]; p = .007). At week 12, IRI increased significantly in the olanzapine monotherapy group (mean, 1.74; standard deviation (SD) = 1.11, p < .001), but not in the olanzapine plus probiotics and dietary fiber group (mean 0.47, SD = 2.16, p = .35) with an estimated mean difference of -0.95 between the two groups [95% CI, -1.77 to -0.14]; p = .022).
Conclusions:
These results provide support for the efficacy and safety of probiotics plus dietary fiber in attenuating antipsychotic-induced weight gain in drug-naïve, first-episode schizophrenia patients.
... The gut microbiota (GM) has a variety of influences on the health status of the host human (1). Also, it can be hypothesized that the GM may influence pain processing and perception. ...
: The gut microbiota (GM) plays an important role in gut-brain communication, and the ‘gut-brain axis’ has attracted much attention as a factor influencing human host health. We previously reported that pain perception may be associated with GM composition in males. The aim of this study was to investigate the relationship between GM composition and pain perception among 42 healthy female university students in Japan. Pain perception was evaluated by pressure pain threshold (PPT), current perception threshold (CPT), temporal summation of pain (TSP), conditioned pain modulation (CPM), and a questionnaire on psychological state. CPT was stimulated at 5, 250, and 2,000 Hz, which reflected the thresholds of the C, Aδ, and Aβ fibers, respectively. Also, GM composition was estimated using 16S rRNA analysis. The lower alpha diversity was associated with, the lower PPT (rs = 0.330, P < 0.05) and CPT of 2000 Hz (re = 0.339, P < 0.05). Furthermore, alpha diversity was identified as an explanatory variable for PPT (β = 0.424, P < 0.01) and TSP (β = -0.317, P < 0.05), alpha diversity and state anxiety for CPT of 2000 Hz (β = 0.321, P < 0.05), and state anxiety for CPT of 250 Hz (β = 0.320, P < 0.05). However, there was no relationship between the rate of major phylum and pain perception.
... The human digestive tract is populated by a diverse array of bacterial species, though these are highly variable, differing with diet, geography, and genetics [1][2][3][4]. Dysbioses in the gut microbiome have been associated with a wide range of chronic and infectious diseases [3,5,6]. ...
Norovirus infection causing acute gastroenteritis could lead to adverse effects on the gut microbiome. We assessed the association of microbiome diversity with norovirus infection and secretor status in patients from Veterans Affairs Medical Centers. Alpha diversity metrics were lower among patients with acute gastroenteritis but were similar for other comparisons.
... Microorganisms that make up the human microbiota; bacteria, fungi, viruses, archaea, and parasites, and most of the microorganisms in the intestinal contents are bacteria and almost all of the bacteria are anaerobic bacteria in the literature [19]. As a result of the analyzes made in our article study, it was verified that the information is correct as a result of the performed test. ...
Suicidal cases are criminal cases that either should be prevented or be investigated forensically after occurring. One of the aims of our study is that arrange the bacterial flora-one of the biological factors-in the gut to reduce suicide cases. In our study, we compared the bacterias which are based in the gut flora of suicidal death with the control group among the 103 autopsy materials collected. In this study, besides the classic microbial and biochemical methods, we also used the Real-Time PCR and Droplet Digital PCR methods. According to the result of our study, it is determined that Bacteroides sp., Clostridium sp., Lactobacillus sp. and Bifidobacterium sp. which affect suicide are significantly different than control groups. It is thought that probiotic or prebiotic supplementation of individuals with intestinal flora imbalance may be beneficial about reduce the suicidal cases which are caused by depression and anxiety. Therefore arranging of the gut flora may decrease the suicidal cases besides increasing the academic studies shall have considerable importance and may gain favor in this sense.
... The human gut hosts tens of thousands of microorganisms, up to 100 trillion microbes, which are collectively referred to as the gut microbiome (11,12). The four dominant bacterial phyla in the human gut are Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria (13), and the Bacteroidetes and Firmicutes phyla constitute the vast majority of the dominant human gut microbiota (14). There is considerable microbial diversity among different individuals because of variations in age, genetics, FIGURE 1 | (A) Factors impacting the gut microbiome in a sex-specific manner. ...
There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.
... There is growing evidence that gut microbiota is closely associated with metabolic diseases including type 2 diabetes (25)(26)(27)(28). Specific changes in the diversity of gut microbiota are one of the characteristics of diabetic patients and animals, and diet is one of the most influential factors that impacts the dynamic microbial community ecosystem (29). ...
Dietary intervention is crucial for the prevention and control of diabetes. China has the largest diabetic population in the world, yet no one dietary strategy matches the eating habits of the Chinese people. To explore an effective and acceptable dietary pattern, this study uses oat and buckwheat compound (OBC) as a staple food substitute and explored its effects on diabetic Sprague–Dawley rats. The model of diabetic rats was established by combining high-calorie feed and streptozotocin (STZ) injection. The dietary intervention for the seven groups, including a normal control group, a model control group, a metformin control group, a wheat flour control group, and three OBC groups with different doses, started from the beginning of the experiment and lasted for 11 weeks, two consecutive injections of STZ in small doses were operated at the 6th week. General states, glucose metabolism, and lipid metabolism indexes were measured. Antioxidant and inflammatory indexes and pathologic changes of kidney and liver tissues were tested. Changes in kidney and ileum ultramicrostructure were detected. What's more, ileal epithelial tight junction proteins and gut microbiota were analyzed. Significant decreases in fasting blood glucose (FBG), glucose tolerance, serum insulin, and insulin resistance were observed in rats intervened with OBC, and these rats also showed a higher level of superoxide dismutase (SOD) together with improved lipid metabolism, attenuated inflammation, and liver and kidney injuries. In addition, in OBC groups, the intestinal barrier was improved, and the disturbance of gut microbiota was reduced. These results suggest that OBC has health-promoting effects for diabetic rats, and since oat and buckwheat are traditionally consumed grains in China, OBC could be a potential and easy-to-accept staple food substitute for the dietary pattern for Chinese.
Drug induced liver injury (DILI) is a kind of liver dysfunction which caused by drugs, and gut microbiota could affect liver injury. However, the relationship between gut microbiota and its metabolites in DILI patients is not clear. The total gut microbiota DNA was extracted from 28 DILI patient and 28 healthy control volunteers (HC) and 16S rDNA gene were amplified. Next, differentially metabolites were screened. Finally, the correlations between the diagnostic strains and differentially metabolites were studied.The richness and uniformity of the bacterial communities decreased in DILI patients, and the structure of gut microbiota changed obviously. Enterococcus and Veillonella which belong to Firmicutes increased in DILI, and Blautia and Ralstonia which belong to Firmicutes, Dialister which belongs to Proteobacteria increased in HC. In addition, these diagnostic OTUs of DILI were associated with the DILI damage mechanism. On the other hands, there were 66 differentially metabolites between DILI and HC samples, and these metabolites were mainly enriched in pyrimidine metabolism and steroid hormone biosynthesis pathways. Furthermore, the collinear network map of the key microbiota-metabolites were constructed and the results indicated that Cortodoxone, Prostaglandin I1, Bioyclo Prostaglandin E2 and Anacardic acid were positively correlated with Blautia and Ralstonia , and negatively correlated with Veillonella .This study analyzed the changes of DILI from the perspective of gut microbiota and metabolites. Key strains and differentially metabolites of DILI were screened and the correlations between them were studied. This study further illustrated the mechanism of DILI.
Prenatal maternal stress (PNMS)—characterized by exposure to stress, anxiety, depression, or intimate partner violence—has been linked to biological alterations in infants, including disruptions to their intestinal microbiota, which have long‐term implications for children's developmental outcomes. Significant research has been done examining the effects of PNMS on the microbiome in animals, but less is known about these effects in human research. The current systematic review aimed to synthesize current findings on the association between PNMS and mother and infant microbiomes. Medline, Embase, PsycInfo, Web of Science, and Eric databases were searched through to February 2022. A total of eight studies ( n = 2219 infants, 2202 mothers) were included in the qualitative synthesis. Findings provided promising evidence of the role that PNMS plays in altering the microbial composition, diversity, and gut immunity in mothers and infants. Notably, majority of included studies found that higher PNMS was linked to increases in genera from the phylum Proteobacteria . The factors influencing these effects are explored including nutrition, birth mode, and parenting behaviors. Potential interventions to mitigate the adverse effects of PNMS are discussed, along with recommendations for future studies with longitudinal designs to better understand the appropriate type and timing of interventions needed to promote “healthy” maternal and infant microbial functioning.
Diesel particulate matter (DPM) is a major component of Fine Particulate Matter (PM2.5), which has been recognized by the World Health Organization under the name "Class I Carcinogen". Lung microbial communities are present widely in the lung tissue of a variety of organisms and play a significant role in the development and progression of lung disease, while cGAS is a DNA receptor that senses the invasion of microbial pathogens and activates the innate immune response. However, the role of cGAS in pulmonary flora-mediated PM2.5-induced lung injury is still largely unknown. With constructed cGAS-/- C57BL/6J mice, we found that lung damage, inflammation, and genetic damage induced by DPM were significantly blocked. With antibiotic-treated C57BL/6J mice, we found that healthy lung microbes were able to attenuate DPM-induced lung damage, inflammation, and genetic damage. DPM modified the expression of the cGAS/STING signaling pathway through the lung flora. This study revealed that cGAS signaling pathway played an essential role in lung flora-mediated adverse effects of DPM, which provided new therapeutic targets for lung diseases.
Microorganisms’ flora, which colonize in many parts of our body, stand out as one of the most important components for a healthy life. This microbial organization called microbiome lives in integration with the body as a single and whole organ/system. Perhaps, the human first encounters the microbial activity it carries through the immune system. This encounter and interaction are vital for the development of immune system cells that protect the body against pathogenic organisms and infections throughout life. In recent years, it has been determined that some disruptions in the host-microbiome interaction play an important role in the physiopathology of autoimmune diseases. Although the details of this interaction have not been clarified yet, the focus is on leaky gut syndrome, dysbiosis, toll-like receptor ligands, and B cell dysfunction. Nutritional regulations, prebiotics, probiotics, fecal microbiota transplantation, bacterial engineering, and vaccination are being investigated as new therapeutic approaches in the treatment of problems in these areas. This article reviews recent research in this area.KeywordsMicrobiomeAutoimmunityNeuroinflammationDysbiosisVaccination
Leaky gut
Female patient, 68-years-old, suffering for 42 years from irritable bowel syndrome (IBS) reached to my attention in social media during summer 2020 by complaining miserable experience devastating her life quality. Patient has been resided in Salt lake City, UT for the past 23 years and has been examined by numerous physicians throughout the years. She has been under medication and severe dietary program. She consumed daily dosages of digestive enzyme complex (Holoenzyme™) and Probiotic 10 capsules (Nature’s Bounty™). She had been restricted in consumption of fruits, vegetables, dairy products either cooked or raw. She suffered severe stomachache, bloating and crumpling for hours to come after consuming incompatible food ingredients. The patient communicating only by means of text messages was advised to stop the current medication and consume fermented milk beverages in order to provide sufficient supply of live probiotics. Within a day or two, she started to send complements by experiencing joy and surprise after ingesting fermented milk beverage known as Kefir manufactured by Lifeway™. No pain whatsoever, while being able to ingest various foods and fresh organics. According to the recent communications, it is assumed that patient was diagnosed skeptically and ill-advised by previous practitioners for many years hence devastating her quality of life. Regardless of assigning IBS or confirming any other clinical symptom, the patient simply was suffering from simple physiological disorder caused by incompatible microbial activity in her guts.
Implant Destekli Sabit Protezlerde Protetik Başarısızlık Nedenleri (Derleme)
To understand life in all its varieties, we must undertake to understand our cells and, most particularly, acknowledge that all cells are problem-solving, communicating, self-referential agents. As a result, our traditional conceptions of intelligence and problem-solving must be thoroughly redefined. This radical new approach explains precisely why our human choices are centered within the same cellular rules that enable our cells to seamlessly sustain our lives. While the partnership between our cells and our microbes has largely been thought of as “host” and “guest,” the reciprocal interactions between essential living fractions in holobionts is so intimate that we should regard ourselves as a consensual 'we'. Exploring the extent of the deep integration of our cellular networks yields profound insights about ourselves, our health and well-being, our social systems, and our permanent relationship with the planet and the cosmos.
Infectious agents have been long considered to play a role in the pathogenesis of neurological diseases as part of the interaction between genetic susceptibility and the environment. The role of bacteria in CNS autoimmunity has also been highlighted by changes in the diversity of gut microbiota in patients with neurological diseases such as Parkinson’s disease, Alzheimer disease and multiple sclerosis, emphasizing the role of the gut-brain axis. We discuss the hypothesis of a brain microbiota, the BrainBiota: bacteria living in symbiosis with brain cells. Existence of various bacteria in the human brain is suggested by morphological evidence, presence of bacterial proteins, metabolites, transcripts and mucosal-associated invariant T cells. Based on our data, we discuss the hypothesis that these bacteria are an integral part of brain development and immune tolerance as well as directly linked to the gut microbiome. We further suggest that changes of the BrainBiota during brain diseases may be the consequence or cause of the chronic inflammation similarly to the gut microbiota.
Steam-processed Polygonatum sibiricum (PS) has been used as food for thousands of years. However, fewer studies concentrated on the effects of polysaccharides (SPSP) from the steamed PS on the intestinal tract. With fermentation in vitro, we investigated the impact of SPSP on the fatty acids and microbiotas. Results showed significant increases in short-chain fatty acids (SCFAs) like acetic acid and propionic acid, and long-chain fatty acids (LCFAs) like cis, cis, cis-9,12,15-linolenic acid, cis-6-octadecenoic acid, and cis-9-octadecenoic acid after 12 h. The positive-associated beneficial microbiotas were observed with proliferation like Parabacteroides and Bifidobacterium. Harmful microbiota like Shigella showed decreased abundance. Further, a small molecule polysaccharide was separated from the SPSP with the structure of one glucose and ten fructose, which significantly increased SCFAs and LCFAs contents during fermentation. The potential benefits of SPSP were proved by the analysis of fatty acid levels and the intestinal microbiotas during fermentation.
The digestive system comprises the gastrointestinal track (GI track) and accessory organs/glands. Recent research discoveries prove that in addition to GI track itself, gut microbiota also plays crucial roles in regulating digestive function and other human physiological functionalities as well as pathological processes. We therefore proposed to include gut microbiota into the digestive system, making it now comprise three parts: GI track, digestive glands, and gut microbiota. Gastrointestinal diseases (GI diseases) refer to diseases involving the gastrointestinal tract from mouth through the esophagus, stomach, small intestine, large intestine, and rectum to anus, as well as the accessory organs of digestion, the liver, gallbladder, and pancreas. Gut microbiota are the microorganisms including bacteria, archaea, and microscopic eukaryotes that live in the digestive tracts. This chapter aims to introduce the basics of GI disease and highlight clinical applications of the polypharmacological approaches for the treatment of the GI disease.KeywordsGastrointestinal polypharmacologyGastrointestinal diseasesGut microbiotaHepatitis C virusMultitarget therapy
The gut microbiome is considered as an organ that contributes to the regulation of host metabolism. Mammals possess an ‘extended genome’ of millions of microbial genomes located in the intestine: the microbiome. To date, there is rapidly booming evidence for host–microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to comprehensive systemic signalling and engaging various organs and organ systems, including the central nervous system. As such, the disclosure of differential microbial composition is associated with alterations in behaviour, and cognition has consequently subsidized to establish the microbiota–gut–brain axis as an extension of the well-accepted gut–brain axis concept. Numerous exertions have been focused on demarcating a role for this axis in health and disease, ranging from stress-associated conditions such as depression, anxiety and irritable bowel syndrome (IBS) to neurodevelopmental conditions such as autism. Besides this, the gut–brain axis is also reported to influence brain disorders, e.g. Alzheimer’s disease, Parkinson’s disease and schizophrenia. There is bidirectional communication network that links the enteric and central nervous systems. This network is not merely anatomical, but it encompasses endocrine, humoral, metabolic and immune routes of intercommunication as well. The autonomic nervous system, hypothalamic–pituitary–adrenal (HPA) axis and nerves within the gastrointestinal tract all link the gut and the brain, allowing the brain to influence intestinal activities, including activity of functional immune effector cells, and the gut to influence mood and behaviour, cognition and mental and reproductive health. In this chapter, we have focused on how gut microbiomes influence physical and mental health.
Background and aims: Some chronic intestinal disorders, including irritable bowel syndrome (IBS), coeliac disease (CD), and non-coeliac gluten sensitivity (NCGS), can make some changes to the gut microbiota composition and cause dysbiosis. This study aimed to determine the gut microbiota alterations in CD, NCGS, and IBS patients among the Iranian population compared to healthy controls.
Materials and Methods: In this prospective study, 72 patients, including 15 healthy controls (HC), 30 IBS,12 NCGS, and 15 CD patients were included. IBS, CD, and NCGS were diagnosed based on the Rome IV diagnostic criteria, Modi¦ed Marsh classi¦cation, and gluten challenge test. Stool samples were collected from patients, and after DNA extraction, quantitative real-time PCR (qPCR) was performed for assessing the relative abundance of Firmicutes, Bacteroidetes, Bi¦dobacterium spp., and Lactobacillus spp.
Results: Firmicutes and Lactobacillus spp. were the most and the least abundant phylum in all samples, respectively. In CD patients, Firmicutes phylum was the most signi¦cant relative abundance. Bacteroidetes phylum had a signi¦cant relative abundance in CD
(P<0.01) and NCGS (P<0.05) patients. The relative abundance of Bi¦dobacterium spp. was statistically lower in CD (P<0.05) and IBS patients (P<0.001) compared to the HCs. The Firmicutes to Bacteroidetes ratio was statistically signifcant inNCGS and CD patients compared to the HCs (P = 0.05).
Conclusion: Chronic intestinal diseases, including IBS, CD, and NCGS, can alter the gut microbiota composition.
Background:
Recurrent Clostridium difficile infection is difficult to treat, and failure rates for antibiotic therapy are high. We studied the effect of duodenal infusion of donor feces in patients with recurrent C. difficile infection.
Methods:
We randomly assigned patients to receive one of three therapies: an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor feces through a nasoduodenal tube; a standard vancomycin regimen (500 mg orally four times per day for 14 days); or a standard vancomycin regimen with bowel lavage. The primary end point was the resolution of diarrhea associated with C. difficile infection without relapse after 10 weeks.
Results:
The study was stopped after an interim analysis. Of 16 patients in the infusion group, 13 (81%) had resolution of C. difficile-associated diarrhea after the first infusion. The 3 remaining patients received a second infusion with feces from a different donor, with resolution in 2 patients. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhea and abdominal cramping in the infusion group on the infusion day. After donor-feces infusion, patients showed increased fecal bacterial diversity, similar to that in healthy donors, with an increase in Bacteroidetes species and clostridium clusters IV and XIVa and a decrease in Proteobacteria species.
Conclusions:
The infusion of donor feces was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin. (Funded by the Netherlands Organization for Health Research and Development and the Netherlands Organization for Scientific Research; Netherlands Trial Register number, NTR1177.).
Microbes inhabit virtually all sites of the human body, yet we know very little about the role they play in our health. In recent years, there has been increasing interest in studying human-associated microbial communities, particularly since microbial dysbioses have now been implicated in a number of human diseases [1]–[3]. Dysbiosis, the disruption of the normal microbial community structure, however, is impossible to define without first establishing what “normal microbial community structure” means within the healthy human microbiome. Recent advances in sequencing technologies have made it feasible to perform large-scale studies of microbial communities, providing the tools necessary to begin to address this question [4], [5]. This led to the implementation of the Human Microbiome Project (HMP) in 2007, an initiative funded by the National Institutes of Health Roadmap for Biomedical Research and constructed as a large, genome-scale community research project [6]. Any such project must plan for data analysis, computational methods development, and the public availability of tools and data; here, we provide an overview of the corresponding bioinformatics organization, history, and results from the HMP (Figure 1).
The involvement of the gut microbiota in metabolic disorders, and the ability of whole grains to affect both host metabolism and gut microbial ecology, suggest that some benefits of whole grains are mediated through their effects on the gut microbiome. Nutritional studies that assess the effect of whole grains on both the gut microbiome and human physiology are needed. We conducted a randomized cross-over trial with four-week treatments in which 28 healthy humans consumed a daily dose of 60 g of whole-grain barley (WGB), brown rice (BR), or an equal mixture of the two (BR+WGB), and characterized their impact on fecal microbial ecology and blood markers of inflammation, glucose and lipid metabolism. All treatments increased microbial diversity, the Firmicutes/Bacteroidetes ratio, and the abundance of the genus Blautia in fecal samples. The inclusion of WGB enriched the genera Roseburia, Bifidobacterium and Dialister, and the species Eubacterium rectale, Roseburia faecis and Roseburia intestinalis. Whole grains, and especially the BR+WGB treatment, reduced plasma interleukin-6 (IL-6) and peak postprandial glucose. Shifts in the abundance of Eubacterium rectale were associated with changes in the glucose and insulin postprandial response. Interestingly, subjects with greater improvements in IL-6 levels harbored significantly higher proportions of Dialister and lower abundance of Coriobacteriaceae. In conclusion, this study revealed that a short-term intake of whole grains induced compositional alterations of the gut microbiota that coincided with improvements in host physiological measures related to metabolic dysfunctions in humans.The ISME Journal advance online publication, 4 October 2012; doi:10.1038/ismej.2012.104.
Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.
Increasing understanding of the normal commensal microorganisms in humans suggests that restoring and maintaining the microbiome
may provide a key to preventing colonization and infection with multidrug-resistant organisms (MDROs). Intact communities
of commensals can prevent colonization with MDROs through both competition for space and resources and the complex immunologic
and biochemical interactions that have developed between commensal and host over millennia. Current antimicrobials, however,
exert tremendous collateral damage to the human microbiome through overuse and broadening spectrum, which has likely been
the driving force behind the introduction and proliferation of MDROs. The future direction of infection control and anti-infective
therapy will likely capitalize on an expanding understanding of the protective role of the microbiome by (1) developing and
using more microbiome-sparing antimicrobial therapy, (2) developing techniques to maintain and restore indigenous microbiota,
and (3) discovering and exploiting host protective mechanisms normally afforded by an intact microbiome.
Clostridium difficile infection (CDI) is a common hospital-acquired infection with increasing incidence, severity, recurrence, and associated morbidity and mortality. There are emerging data on the occurrence of CDI in nonhospitalized patients. However, there is a relative lack of community-based CDI studies, as most of the existing studies are hospital based, potentially influencing the results by referral or hospitalization bias by missing cases of community-acquired CDI.
To better understand the epidemiology of community-acquired C. difficile infection, a population-based study was conducted in Olmsted County, Minnesota, using the resources of the Rochester Epidemiology Project. Data regarding severity, treatment response, and outcomes were compared in community-acquired vs. hospital-acquired cohorts, and changes in these parameters, as well as in incidence, were assessed over the study period.
Community-acquired CDI cases accounted for 41% of 385 definite CDI cases. The incidence of both community-acquired and hospital-acquired CDI increased significantly over the study period. Compared with those with hospital-acquired infection, patients with community-acquired infection were younger (median age 50 years compared with 72 years), more likely to be female (76% vs. 60%), had lower comorbidity scores, and were less likely to have severe infection (20% vs. 31%) or have been exposed to antibiotics (78% vs. 94%). There were no differences in the rates of complicated or recurrent infection in patients with community-acquired compared with hospital-acquired infection.
In this population-based cohort, a significant proportion of cases of CDI occurred in the community. These patients were younger and had less severe infection than those with hospital-acquired infection. Thus, reports of CDI in hospitalized patients likely underestimate the burden of disease and overestimate severity.
The human oral microbiome is potentially related to diverse health conditions and high-throughput technology provides the possibility of surveying microbial community structure at high resolution. We compared two oral microbiome survey methods: broad-based microbiome identification by 16S rRNA gene sequencing and targeted characterization of microbes by custom DNA microarray.
Oral wash samples were collected from 20 individuals at Memorial Sloan-Kettering Cancer Center. 16S rRNA gene survey was performed by 454 pyrosequencing of the V3-V5 region (450 bp). Targeted identification by DNA microarray was carried out with the Human Oral Microbe Identification Microarray (HOMIM). Correlations and relative abundance were compared at phylum and genus level, between 16S rRNA sequence read ratio and HOMIM hybridization intensity.
The major phyla, Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Fusobacteria were identified with high correlation by the two methods (r = 0.70∼0.86). 16S rRNA gene pyrosequencing identified 77 genera and HOMIM identified 49, with 37 genera detected by both methods; more than 98% of classified bacteria were assigned in these 37 genera. Concordance by the two assays (presence/absence) and correlations were high for common genera (Streptococcus, Veillonella, Leptotrichia, Prevotella, and Haemophilus; Correlation = 0.70-0.84).
Microbiome community profiles assessed by 16S rRNA pyrosequencing and HOMIM were highly correlated at the phylum level and, when comparing the more commonly detected taxa, also at the genus level. Both methods are currently suitable for high-throughput epidemiologic investigations relating identified and more common oral microbial taxa to disease risk; yet, pyrosequencing may provide a broader spectrum of taxa identification, a distinct sequence-read record, and greater detection sensitivity.
The human gastrointestinal tract is divided into sections, allowing digestion and nutrient absorption in the proximal region to be separate from the vast microbial populations in the large intestine, thereby reducing conflict between host and microbes. In the distinct habitats of the gut, environmental filtering and competitive exclusion between microbes are the driving factors shaping microbial diversity, and stochastic factors during colonization history and in situ evolution are likely to introduce intersubject variability. Adaptive strategies of microbes with different niches are genomically encoded: Specialists have smaller genomes than generalists, and microbes with environmental reservoirs have large accessory genomes. A shift toward a Neolithic diet increased loads of simple carbohydrates and selected for their increased breakdown and absorption in the small intestine. Humans who outcompeted microbes for the new substrates obtained more energy from their diets and prospered, an evolutionary process reflected in modern population genetics. The three-way interactions between human genetics, diet, and the microbiota fundamentally shaped modern populations and continue to affect health globally.
Increasing awareness of the role of intestinal commensal bacteria in the development and modulation of the immune system has led to great interest in the therapeutic potential of probiotics and other bacteria-based strategies for a range of immune-related disorders. Studies in animal models have identified strong immunomodulatory effects of many nonpathogenic bacteria and provided evidence that intestinal microbes can activate a common mucosal immune response and, thus, influence sites distant to the intestine, including the respiratory tract. Respiratory effects of probiotics in animal models have included attenuating allergic airway responses and protecting against respiratory pathogens. Dendritic cells appear central to directing the beneficial immune response to probiotic bacteria and in translating microbial signals from the innate to the adaptive immune system, whereas regulatory T cells are emerging as potentially key effectors of probiotic-mediated responses, particularly in the reduction of allergic inflammation. Despite progress in basic research, clinical trials of probiotics in allergy/asthma and respiratory infection have been highly variable at best, leading to an undermining of confidence in this potential therapeutic strategy. It is clear that there is still much to learn regarding the determinants of the diverse immune responses elicited by different bacterial strains. A deeper knowledge of the interactions between administered probiotics and the existing microbiota, together with an understanding of how the dialogue between microbes and the innate immune system is translated into beneficial/protective responses, will be required before we can achieve clinically effective bacteria-based strategies that maintain and promote respiratory health.
The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles.
Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut.
These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity.
Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS.
In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study.
Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.
Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).
Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this "organ" has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.
Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections.
By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians' microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians.
We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host's immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.
Diet and nutritional status are among the most important modifiable determinants of human health. The nutritional value of food is influenced in part by a person's gut microbial community (microbiota) and its component genes (microbiome). Unraveling the interrelations among diet, the structure and operations of the gut microbiota, and nutrient and energy harvest is confounded by variations in human environmental exposures, microbial ecology, and genotype. To help overcome these problems, we created a well-defined, representative animal model of the human gut ecosystem by transplanting fresh or frozen adult human fecal microbial communities into germ-free C57BL/6J mice. Culture-independent metagenomic analysis of the temporal, spatial, and intergenerational patterns of bacterial colonization showed that these humanized mice were stably and heritably colonized and reproduced much of the bacterial diversity of the donor's microbiota. Switching from a low-fat, plant polysaccharide-rich diet to a high-fat, high-sugar "Western" diet shifted the structure of the microbiota within a single day, changed the representation of metabolic pathways in the microbiome, and altered microbiome gene expression. Reciprocal transplants involving various combinations of donor and recipient diets revealed that colonization history influences the initial structure of the microbial community but that these effects can be rapidly altered by diet. Humanized mice fed the Western diet have increased adiposity; this trait is transmissible via microbiota transplantation. Humanized gnotobiotic mice will be useful for conducting proof-of-principle "clinical trials" that test the effects of environmental and genetic factors on the gut microbiota and host physiology. Nearly full-length 16S rRNA gene sequences are deposited in GenBank under the accession numbers GQ491120 to GQ493997.
Irritable bowel syndrome (IBS) is a common disorder and available therapies have limited efficacy. Mucosal inflammation and alterations in gut microflora may contribute to the development of IBS symptoms, and researchers have hypothesized that probiotics might improve these symptoms. The aim of this study was to perform a systematic review of randomized controlled trials (RCTs) evaluating the efficacy, safety, and tolerability of probiotics in the treatment of IBS.
Comprehensive literature searches of multiple databases were performed. Study selection criteria were as follows: (i) RCTs, (ii) adults with IBS defined by Manning or Rome II criteria, (iii) single or combination probiotic vs. placebo, and (iv) improvement in IBS symptoms and/or decrease in frequency of adverse events reported. Data about study design and results were extracted in duplicate using standardized data extraction forms. Owing to variability in outcome measures, quantitative pooling of data was not feasible.
A total of 16 RCTs met selection criteria. Of those, 11 studies showed suboptimal study design with inadequate blinding, inadequate trial length, inadequate sample size, and/or lack of intention-to-treat analysis. None of the studies provided quantifiable data about both tolerability and adverse events. Bifidobacterium infantis 35624 showed significant improvement in the composite score for abdominal pain/discomfort, bloating/distention, and/or bowel movement difficulty compared with placebo (P<0.05) in two appropriately designed studies. No other probiotic showed significant improvement in IBS symptoms in an appropriately designed study.
B. infantis 35624 has shown efficacy for improvement of IBS symptoms. Most RCTs about the utility of probiotics in IBS have not used an appropriate study design and do not adequately report adverse events. Therefore, there is inadequate data to comment on the efficacy of other probiotics. Future probiotic studies should follow Rome II recommendations for appropriate design of an RCT.
We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.
• energy balance/obesity
• host-microbial interactions
• intestinal bacterial diversity
• ob/ob mice
• phylogenetics
Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.
The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.
Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776)
Purpose of review:
To illustrate how microbes might participate in the pathogenesis of neuropsychiatric illness by triggering the production of autoantibodies that bind to brain targets.
Recent findings:
Some studies link exposure to infectious agents to development of brain disorders; others have identified autoantibodies in individuals with these conditions without finding evidence of pathogens. Neither line of work demonstrates consistent associations between a specific neuropsychiatric disease and a particular environmental trigger or immune marker. Growing evidence suggests that the microbiome conditions host immunity to microbes and xenobiotics, and regulates autoimmune responses that can affect the central nervous system (CNS). The presence of CNS receptors for cytokines and other immune molecules underscores the importance of brain-immune crosstalk in maintaining normal function. An increased prevalence of familial autoimmunity, exposure to pathogens prenatally and postnatally, and findings of antibrain antibodies is common in disorders as diverse as schizophrenia, obsessive-compulsive disorder and autism, and suggests that differences in exposure timing and genetic vulnerability toward autoimmunity are important determinants of neuropsychiatric outcomes.
Summary:
Microbes, both pathogenic and commensal, can induce autoantibodies that bind to brain and affect behavior in susceptible hosts. Interventions that correct the microbial balance or diminish autoantibody binding may be effective in diverse neuropsychiatric conditions mediated by autoimmunity.
Gut microbiota alterations are increasingly being recognized as an important factor in the pathogenesis and pathophysiology of Irritable bowel syndrome (IBS). The onset of IBS symptoms after a bout of gastroenteritis comprises one of the strongest indications for the importance of gut microbiota for IBS. Moreover, recent studies have identified several susceptibility genes for IBS involved in the innate immunity and recognition of bacteria but also maintaining the integrity of the intestinal barrier. During recent years, it has also been demonstrated that IBS patients, or subgroups thereof, may have an altered microbiota composition relative to healthy individuals, mainly based on the analysis of fecal microbiota. Moreover, a positive effect of treatment with non-absorbable antibiotics and probiotics in IBS provides further indirect support for the relevance of gut microbiota alterations in IBS.
The vital roles that intestinal flora, now called microbiota, have in maintaining our health are being increasingly appreciated. Starting with birth, exposure to the outside world begins the life-long intimate association our microbiota will have with our diet and environment, and initiates determination of the post-natal structural and functional maturation of the gut. Moreover, vital interactions of the microbiota with our metabolic activities, as well as with the immunological apparatus that constitutes our major defense system against foreign antigens continues throughout life. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and non-gastrointestinal diseases including Clostridium difficile infection (CDI). It has become recognized that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic CDI, and effect a seemingly safe, relatively inexpensive, and rapidly effective cure in the vast majority of patients so treated. In addition, FMT has been used to treat an array of other gastrointestinal and non-gastrointestinal disorders, although experience in these other non-CDI diseases is in its infancy. More work needs to be done with FMT to ensure its safety and optimal route of administration. There is a conceptual sea change that is developing in our view of bacteria from their role only as pathogens to that of being critical to health maintenance in a changing world. Future studies are certain to narrow the spectrum of organisms that need to be given to patients to cure disease. FMT is but the first step in this journey.Am J Gastroenterol advance online publication, 15 January 2013; doi:10.1038/ajg.2012.450.
Indigenous microbiota are an essential component in the modern concept of human health, but the composition and functional characteristics of a healthy microbiome remain to be precisely defined. Patterns of microbial colonization associated with disease states have been documented, but the health-associated microbial patterns and their functional characteristics are less clear. A healthy microbiome, considered in the context of body habitat or body site, could be described in terms of ecologic stability (i.e., ability to resist community structure change under stress or to rapidly return to baseline following a stress-related change), by an idealized (presumably health-associated) composition or by a desirable functional profile (including metabolic and trophic provisions to the host). Elucidation of the properties of healthy microbiota would provide a target for dietary interventions and/or microbial modifications aimed at sustaining health in generally healthy populations and improving the health of individuals exhibiting disrupted microbiota and associated diseases.
Clostridium difficile was first described as a cause of diarrhea in 1978 and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes. In addition, several novel risk factors and newer treatment methods are emerging, including fidaxomicin therapy, treatment using monoclonal antibodies, and fecal microbiota transplantation, that have shown promise for the treatment of C difficile infection. This review focuses on the changing epidemiology, risk factors, and newer methods for treatment of C difficile infection.
The healthy human gut supports a complex and diverse microbiota, dominated by bacterial phylotypes belonging to Bacteroidetes and Firmicutes. In the inflamed gut, overall diversity decreases, coincident with a greater representation of Proteobacteria. There is growing evidence supporting an important role for human gut bacteria in mucosal immunity; interactions at the level of both intestinal and colonic epithelial cells, dendritic cells, and T and B immune cells have been documented. These interactions influence gut barrier and defense mechanisms that include antimicrobial peptide and secretory IgA synthesis. The functional effects of commensal bacteria on T helper cell differentiation have led to the emerging concept that microbiota composition determines T effector- and T regulatory-cell balance, immune responsiveness, and homeostasis. The importance of this biology in relation to immune homeostasis, inflammatory bowel disease, and the rising incidence of autoimmune diseases will be discussed. The detailed description of the human gut microbiota, integrated with evidence-based mechanisms of immune modulation, provides an exciting platform for the identification of next-generation probiotics and related pharmaceutical products.
The human gut is home to vast numbers of bacteria (gut microbiota), which outnumber the cells in the human body by an order of magnitude. The gut microbiota has coevolved with humans and can be considered an organ of similar size as the liver, containing more than 1,000 cell types (bacterial species) and encoding 150-fold more genes than are present in the human genome. Accordingly, the gut microbiota may have profound effects on various host responses, either directly or indirectly, by modifying food components or endogenously produced molecules into signaling molecules. Recent findings suggest that an altered gut microbial composition is associated with inflammatory bowel disease and obesity, indicating that the gut microbiota should be considered a contributing factor in several common diseases.
Diet-derived carbohydrates that are not fully digested in the upper gut, known as nondigestible carbohydrates, provide a major source of energy for bacteria that colonize the human large intestine. It is well established that dietary intake of nondigestible carbohydrates influences microbial fermentation and total bacterial numbers in the colon. Recent evidence from molecular ecology has also shown that the amount and type of nondigestible carbohydrates (e.g., resistant starch, non-starch polysaccharides, and prebiotics) influences the species composition of the intestinal microbiota both in short-term dietary interventions and in response to habitual long-term dietary intake. Interindividual variation in gut microbiota may, in part, reflect differences in dietary intake, but the response of the gut microbiota to dietary change can also differ among individuals. As a better understanding is gained of the impact of different groups of bacteria on host metabolism, the ability to manipulate the microbiota through diet should provide a route for delivering health benefits.
The prevalence of allergic diseases continues to rise globally in developed countries. Since the initial proposal of the hygiene hypothesis, there has been increasing evidence to suggest that the intestinal microbiota, particularly during early infancy, plays a critical role in regulating immune responses associated with the development of atopy. This review evaluates the key epidemiologic and mechanistic data published to date.
Epidemiological data have provided the framework for animal studies investigating the importance of gut commensals in allergy development. These studies provide new insights about the microbial regulation of mucosal immune responses inside and outside the gut, and how these effects may drive allergic inflammation in susceptible individuals. Specific immune cells have been identified as mediators of these microbiota-regulated allergic responses.
In the last year, technological advances have provided us with a better understanding of the gut microbiome in healthy and allergic individuals. Recent studies have identified the associations between particular gut microbes and different disease phenotypes, as well as identified immune cells and their mediators involved in allergy development. This research has provided a number of host and microbe targets that may be used to develop novel therapies suitable for the treatment or prevention of allergic diseases.
The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD). Faecal microbiota transplantation (FMT) has been used for the management of IBD as well as infectious diarrhoea.
To undertake a systematic review of FMT in patients with IBD.
The systematic review followed Cochrane and PRISMA recommendations. Nine electronic databases were searched in addition to hand searching and contacting experts. Inclusion criteria were reports (RCT, nonrandomised trials, case series and case reports) of FMT in patients with IBD.
Of the 5320 articles identified, 17 fulfilled the inclusion criteria, none of which were controlled trials. There were nine case series/case reports of patients receiving FMT for management of their IBD, and eight where FMT was for the treatment of infectious diarrhoea in IBD. These 17 articles reported on 41 patients with IBD (27 UC, 12 Crohn's, 2 unclassified) with a follow-up period of between 2 weeks and 13 years. Where reported, FMT was administered via colonoscopy/enema (26/33) or via enteral tube (7/33). In patients treated for their IBD, the majority experienced a reduction of symptoms (19/25), cessation of IBD medications (13/17) and disease remission (15/24). There was resolution of C. difficile infection in all those treated for such (15/15).
Whilst the available evidence is limited and weak, it suggests that faecal microbiota transplantation has the potential to be an effective and safe treatment for IBD, at least when standard treatments have failed. Well-designed randomised controlled trials are required to investigate these findings.
Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).
The Human Genome Project was completed a decade ago, leaving a legacy of process, tools, and infrastructure now being turned to the study of the microbes that reside in and on the human body as determinants of health and disease, and has been branded "The Human Microbiome Project." Of the various niches under investigation, the human gut houses the most complex and abundant microbial community and is an arena for important host-microbial interactions that have both local and systemic impact. Initial studies of the human microbiome have been largely descriptive, a testing ground for innovative molecular techniques and new hypotheses. Methods for studying the microbiome have quickly evolved from low-resolution surveys of microbial community structure to high-definition description of composition, function, and ecology. Next-generation sequencing technologies combined with advanced bioinformatics place us at the doorstep of revolutionary insight into the composition, capability, and activity of the human intestinal microbiome. Renewed efforts to cultivate previously "uncultivable" microbes will be important to the overall understanding of gut ecology. There remain numerous methodological challenges to the effective study and understanding of the gut microbiome, largely relating to study design, sample collection, and the number of predictor variables. Strategic collaboration of clinicians, microbiologists, molecular biologists, computational scientists, and bioinformaticians is the ideal paradigm for success in this field. Meaningful interpretation of the gut microbiome requires that host genetic and environmental influences be controlled or accounted for. Understanding the gut microbiome in healthy humans is a foundation for discovering its influence in various important gastrointestinal and nutritional diseases (eg, inflammatory bowel disease, diabetes, and obesity), and for rational translation to human health gains.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder that may be triggered by enteric pathogens and has also been linked to alterations in the microbiota and the host immune response. The authors performed a detailed analysis of the faecal microbiota in IBS and control subjects and correlated the findings with key clinical and physiological parameters.
The authors used pyrosequencing to determine faecal microbiota composition in 37 IBS patients (mean age 37 years; 26 female subjects; 15 diarrhoea-predominant IBS, 10 constipation-predominant IBS and 12 alternating-type IBS) and 20 age- and gender-matched controls. Gastrointestinal and psychological symptom severity and quality of life were evaluated with validated questionnaires and colonic transit time and rectal sensitivity were measured.
Associations detected between microbiota composition and clinical or physiological phenotypes included microbial signatures associated with colonic transit and levels of clinically significant depression in the disease. Clustering by microbiota composition revealed subgroups of IBS patients, one of which (n=15) showed normal-like microbiota composition compared with healthy controls. The other IBS samples (n=22) were defined by large microbiota-wide changes characterised by an increase of Firmicutes-associated taxa and a depletion of Bacteroidetes-related taxa.
Detailed microbiota analysis of a well-characterised cohort of IBS patients identified several clear associations with clinical data and a distinct subset of IBS patients with alterations in their microbiota that did not correspond to IBS subtypes, as defined by the Rome II criteria.
The distal gut and its associated microbiota is a new frontier in the quest to understand human biology and evolution. The renaissance in this field has been partly driven by advances in sequencing technology and also by the application of a variety of 'omic' technologies in a systems biology framework. In the initial stages of understanding what constitutes the gut, culture-independent methods, primarily inventories of 16S rRNA genes, have provided a clear view of the main taxonomic groups of Bacteria in the distal gut and we are now moving towards defining the functions that reside in the distal gut microbiome. This review will explore recent advances in the area of the distal gut and the use of a variety of omic approaches to determine what constitutes this fascinating collection of microbes.
The prevalence of obesity and related disorders such as metabolic syndrome has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. As most findings in this field of research are based on mouse studies, the relevance to human biology requires further investigation.