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Gut Bacteria in Health and Disease
Abstract
A new era in medical science has dawned with the realization of the critical role of the "forgotten organ," the gut micro-biota, in health and disease. Central to this beneficial interaction between the microbiota and host is the manner in which bacteria and most likely other microorganisms contained within the gut communicate with the host's immune system and participate in a variety of metabolic processes of mutual benefit to the host and the microbe. The advent of high-throughput methodologies and the elaboration of sophisticated analytic systems have facilitated the detailed description of the composition of the microbial constituents of the human gut, as never before, and are now enabling comparisons to be made between health and various disease states. Although the latter approach is still in its infancy, some important insights have already been gained about how the microbiota might influence a number of disease processes both within and distant from the gut. These discoveries also lay the groundwork for the development of therapeutic strategies that might modify the microbiota (eg, through the use of probiot-ics). Although this area holds much promise, more high-quality trials of probiotics, prebiotics, and other microbiota-modifying approaches in digestive disorders are needed, as well as laboratory investigations of their mechanisms of action.
... The relationship between some gut flora and humans is not merely commensal (a non-harmful coexistence), but rather a mutualistic relationship (Sherwood, et al. [11]). Some human gut microorganisms benefit the host by fermenting dietary fiber into short-chain fatty acids (SCFAs), such as acetic acid and butyric acid, which are then absorbed by the host (Quigley, et al. [17,18). Intestinal bacteria also play a role in metabolizing bile acids, sterols, and xenobiotics (Sherwood, et al. [11,18]).The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ (Clarke, et al. [18]) and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions (Quigley, et al. [17,19]). ...
... Some human gut microorganisms benefit the host by fermenting dietary fiber into short-chain fatty acids (SCFAs), such as acetic acid and butyric acid, which are then absorbed by the host (Quigley, et al. [17,18). Intestinal bacteria also play a role in metabolizing bile acids, sterols, and xenobiotics (Sherwood, et al. [11,18]).The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ (Clarke, et al. [18]) and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions (Quigley, et al. [17,19]). These microorganisms perform a host of useful functions (Table 1), such as fermenting unused energy substrates, training the immune system via end products of metabolism like propionate and acetate, preventing growth of harmful species, regulating the development of the gut, producing vitamins for the host (such as biotin and vitamin K), and producing hormones to direct the host to store fats (Sherwood, et al. [11]). ...
... The biosynthesis of bioactive compounds (indole and certain other derivatives) from tryptophan is carried out by Without gut flora, the human body would be unable to utilize some of the undigested carbohydrates it consumes, because some types of gut flora have enzymes that human cells lack for breaking down certain polysaccharides (Clarke, et al. [18). Carbohydrates that humans cannot digest without bacterial help include certain starches, fiber, oligosaccharides, and sugars that the body failed to digest and absorb like lactose in the case of lactose intolerance and sugar alcohols, mucus produced by the gut, and proteins (Quigley, et al. [17,18]). ...
... The microbiome is interconnected with the host physiology and pathophysiology [35] and plays an important role in human health [36]. Considering the comparatively deeper understanding of the function of bacteria compared to the other microbiota members and, since the majority of these microorganisms reside in our gastrointestinal tract [37], bacteria from the GM will be the primary focus of this review. ...
... The ratio of Bacillota to Bacteroidota is considered to be important for gut health [33] and its stability may also be beneficial for the innate immune system [38]. The microbiota plays an important role in protecting the host from pathogenic species invasion by producing nonspecific fatty acids, peroxides, and highly specific bacteriocins that can inhibit or kill other harmful bacteria, and certain strains release proteases capable of deactivating bacterial toxins [37,41,42]. ...
... In addition to the associations between TMAO and major adverse cardiovascular events and hypertension, a link has been established between all causes mortality, CVD mortality, diabetes mellitus, cancer, and renal function through the increase in renal fibrosis and dysfunction and a decrease in glomerular filtration rate [52]. Excessive use of antibiotics eliminates or suppresses many components of the normal microbiota, setting the stage for pathogens' growth and disease progression [37]. Antibioticassociated diarrhea, particularly its most lethal manifestation, Clostridium difficile colitis, is a prime example of this dysregulation [37]. ...
Heart failure (HF) is a debilitating disease with a significant clinical and economic impact worldwide. Multiple factors seem to increase the risk of developing HF, such as hypertension, obesity and diabetes. Since chronic inflammation plays a significant role in HF pathophysiology and gut dysbiosis is associated with low-grade chronic inflammation, the risk of cardiovascular diseases is likely modulated by the gut microbiome (GM). Considerable progress has been made in HF management. However, there is a need to find new strategies to reduce mortality and increase the quality of life, mainly of HFpEF patients, since its prevalence continues to rise. Recent studies validate that lifestyle changes, such as diet modulation, represent a potential therapeutic approach to improve several cardiometabolic diseases, although their effects on the GM and its indirect cardiac impact still warrant further research. Hence, in this paper, we aim to clarify the link between HF and the human microbiome.
... Each individual is carrying 3 to 6 pounds of bacteria and other microbes at all times, with approximately 3 million protein-coding genes [44]. There are various microbial niches that are in harmony with the normal physiologic processes of the human body [45]. The host's homeostasis is significantly influenced by the gut microbiota. ...
... The gut microbiota can have a major impact on health and become disrupted during certain pathological conditions. Environmental factors can also disrupt gut microbial communities in genetically vulnerable individuals, resulting in dysregulation of the host's innate and adaptive immune systems, resulting in the emergence of different illnesses [45]. The interplay between the immune system and the altered gut microbiota has been shown to affect the etiology of various diseases in recent years, including cancer, inflammatory bowel syndrome, metabolic syndrome and nonalcoholic fatty liver disease [59][60][61][62][63] and many autoimmune diseases (e.g. ...
Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immu-nological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.
... Various factors may prompt the changes in the organization and functioning of gut-microbiota, for example, more importantly, an imbalanced diet, then environmental conditions, low immunity-related health conditions, or treatment with prescribed antibiotics. Consequently, frequently imbalanced gut-microbiota may result in several gut disorders and chronic diseases [6]. ...
... That would help to understand the mechanism by which the gut microbiota influence the general health of a person. There are research reports on the role and effectiveness of gut microbiota in the mitigation of several diseases, for instance, gut inflammation, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colorectal cancer (CRC) [1][2][3][4][5][6][7]. Therefore, the routine intake of dietary components including prebiotics and probiotics, has been reported to be influential in sustaining health, as well as with their proven potential as psychobiotics for cognitive health issues treatment through the mechanism of gut-brain signaling [8]. ...
Usually, everyday meals constitute materials and ingredients for food preparation derived from different agricultural sources. Although most customers are aware of the benefits of a balanced diet, they mainly focus on a diet based on the daily requirements of protein, fat, and carbohydrates in their meals. However, the vital aspect of the including dietary fibers in diets is overlooked, which is equally important as is the daily requirement of calories and protein intake for maintaining the muscle mass. Some societies consume a diet heavily based on animal-sourced materials, which is deficient in components of plant-derived beneficial fibers. In such consumers, the smooth functioning of the digestive system and the overall metabolism could be affected in due course of time. As a result, their excretion system would be adversely influenced. The long-term irregularities in the alimentary system might be a cause of the initiation of a problem, particularly in the colon. Foods are natural therapeutics to sustain the healthy functioning of the gastrointestinal tract (GIT), which is also interconnected with other systems impacting the physiology of the human body. Consumers generally select their meals according to their personal choice and taste, and their nutrition is geographically influenced. However, the dietary fibers (prebiotics) sourced from various agricultural materials can be easily included as a constituent of food for the survival and metabolism of probiotic cultures resident in consumers’ GIT. This article aims to review information available on plant-derived dietary fibers and their role in the functioning of probiotic microorganisms resident in the gastrointestinal tract, which is important for managing gut health, thereby minimizing inflammatory gut issues.
... Colonization of the human gut with microbes begins immediately at birth, upon passage through the birth canal where fetuses are exposed to a variety of microorganisms [7]. There are several factors that influence colonization, the most important ones include the following gestational age, mode of delivery (vaginal birth vs assisted delivery), diet (breast milk vs formula), pregnant women sanitation level and antibiotic exposure [8]. After the first year of life, the intestinal microbiota starts to resemble that of a young adult. ...
... Moreover, recent research shows an overabundance of Shigella in the microbiome associated with the mucous membrane of patients diagnosed with adenoma [31]. 8. Campylobacter jejuni (C. ...
The understanding and explanation of inflammation-dysplasia-cancer sequence is challenging. The gut microbiota is an important factor for the intestine wall. The changes in bacteria quality and/or quantity (dysbiosis) may begin the colon inflammation. This paper reviewed the gut microbiome risk factors which may lead to colon cancer.
... Generally, within a species, there is a set of microorganisms that are consistent across individuals; however, as described above, the overall composition, both in bacterial concentration as well as species diversity, of the microbiome can vary greatly between individuals. These changes can occur in response to external as well as endogenous physiological processes, including, but not limited to, aging, dietary changes, the use of antibiotics, genetic differences, and the response to infection [65,66]. Dysregulation, a state of imbalance in the composition or function of microbial taxa, of the gut microbiome can lead to significant inflammatory and autoimmune conditions [65,67]. ...
... These changes can occur in response to external as well as endogenous physiological processes, including, but not limited to, aging, dietary changes, the use of antibiotics, genetic differences, and the response to infection [65,66]. Dysregulation, a state of imbalance in the composition or function of microbial taxa, of the gut microbiome can lead to significant inflammatory and autoimmune conditions [65,67]. There is a large drive to understand how these factors influence the microbiome to potentially develop interventions to prevent negative health outcomes [66,68], yet overall research in the field is still in its infancy. ...
The human gut, required for ingesting and processing food, extracting nutrients, and excreting waste, is made up of not just human tissue but also trillions of microbes that are responsible for many health-promoting functions. However, this gut microbiome is also associated with multiple diseases and negative health outcomes, many of which do not have a cure or treatment. One potential mechanism to alleviate these negative health effects caused by the microbiome is the use of microbiome transplants. Here, we briefly review the gut’s functional relationships in laboratory model systems and humans, with a focus on the different diseases they directly affect. We then provide an overview of the history of microbiome transplants and their use in multiple diseases including Alzheimer’s disease, Parkinson’s disease, as well as Clostridioides difficile infections, and irritable bowel syndrome. We finally provide insights into areas of research in which microbiome transplant research is lacking, but that simultaneously may provide significant health improvements, including age-related neurodegenerative diseases.
... The intestinal tract is not only the largest digestive organ in the human body, but also the habitat of a diverse population of microorganisms. The intestinal microflora include symbiotic microorganisms that colonize the intestinal tract and grow synergistically with epithelial cells [1]. This diverse community, comprising bacteria, fungi, viruses, and bacteriophages, is essential to the maintenance of intestinal homeostasis [2]. ...
... This type of chip is commonly used for research on gas-liquid interfaces and the endothelial-epithelial barrier. (B) Construction of a microfluidic intestinal chip with the capacity for microbial co-culture: 1 Intestinal epithelial cells are extracted from the human body via biopsy. 2 The obtained epithelial cells are then cultured in a microfluidic intestinal chip. ...
Microfluidics is a system involving the treatment or manipulation of microscale (10−9 to 10−18 L) fluids using microchannels (10 to 100 μm) contained on a microfluidic chip. Among the different methodologies used to study intestinal microorganisms, new methods based on microfluidic technology have been receiving increasing attention in recent years. The intestinal tracts of animals are populated by a vast array of microorganisms that have been established to play diverse functional roles beneficial to host physiology. This review is the first comprehensive coverage of the application of microfluidics technology in intestinal microbial research. In this review, we present a brief history of microfluidics technology and describe its applications in gut microbiome research, with a specific emphasis on the microfluidic technology-based intestine-on-a-chip, and also discuss the advantages and application prospects of microfluidic drug delivery systems in intestinal microbial research.
... Given that T2D progression is a result of both environmental and genetic factors, a higher T2D risk profile observed in Asian ethnicities at low body mass index (BMI) (Haldar et al., 2015) has been suggested to reflect a general inability to adapt to the Western lifestyle and dietary changes popularized with the rise of urbanization and increased globalization over the past two centuries (Akiyama, 2008). As the gut microbiota plays a prominent role in regulating host metabolic homeostasis (Sears, 2005;LeBlanc et al., 2013;Quigley, 2013;Clarke et al., 2014;Duvallet et al., 2017), the utility of microbial community characteristics as non-invasive diagnostic indicators of health has in recent years become widely recognized (Duvallet et al., 2017). However, although associations between disease pathogenicity and the gut microbiota have been established, the taxonomic composition is highly personalized among individuals (Gaulke and Sharpton, 2018) and the noise projected strongly influences the accuracy of microbiota-based investigations. ...
Obesity-related metabolic diseases such as type 2 diabetes (T2D) are major global health issues, affecting hundreds of millions of people worldwide. The underlying factors are both diverse and complex, incorporating biological as well as cultural considerations. A role for ethnicity – a measure of self-perceived cultural affiliation which encompasses diet, lifestyle and genetic components – in susceptibility to metabolic diseases such as T2D is well established. For example, Asian populations may be disproportionally affected by the adverse ‘TOFI’ (Thin on the Outside, Fat on the Inside) profile, whereby outwardly lean individuals have increased susceptibility due to excess visceral and ectopic organ fat deposition. A potential link between the gut microbiota and metabolic disease has more recently come under consideration, yet our understanding of the interplay between ethnicity, the microbiota and T2D remains incomplete. We present here a 16S rRNA gene-based comparison of the fecal microbiota of European-ancestry and Chinese-ancestry cohorts with overweight and prediabetes, residing in New Zealand. The cohorts were matched for mean fasting plasma glucose (FPG: mean ± SD, European-ancestry: 6.1 ± 0.4; Chinese-ancestry: 6.0 ± 0.4 mmol/L), a consequence of which was a significantly higher mean body mass index in the European group (BMI: European-ancestry: 37.4 ± 6.8; Chinese-ancestry: 27.7 ± 4.0 kg/m ² ; p < 0.001). Our findings reveal significant microbiota differences between the two ethnicities, though we cannot determine the underpinning factors. In both cohorts Firmicutes was by far the dominant bacterial phylum (European-ancestry: 93.4 ± 5.5%; Chinese-ancestry: 79.6 ± 10.4% of 16S rRNA gene sequences), with Bacteroidetes and Actinobacteria the next most abundant. Among the more abundant (≥1% overall relative sequence abundance) genus-level taxa, four zero-radius operational taxonomic units (zOTUs) were significantly higher in the European-ancestry cohort, namely members of the Subdoligranulum , Blautia , Ruminoclostridium, and Dorea genera. Differential abundance analysis further identified a number of additional zOTUs to be disproportionately overrepresented across the two ethnicities, with the majority of taxa exhibiting a higher abundance in the Chinese-ancestry cohort. Our findings underscore a potential influence of ethnicity on gut microbiota composition in the context of individuals with overweight and prediabetes.
... In general, IBD patients tend to have reduced bacterial diversity and a disorganized gut microbiota structure compared with healthy controls. In healthy human feces, Firmicutes and Bacteroidetes were the dominant bacterial strains at the phylum level [26]. The abundance of a major member of Firmicutes, F. prausnitzii, is significantly reduced in IBD patients and is associated with the risk of disease recurrence [7,8,17]. ...
Background
Emerging evidence has shown that extracellular vesicles (EVs) derived from gut bacteria play a crucial role in microbiota-host interactions. Here, we aimed to evaluate the attenuating effect of EVs derived from a reduced commensal bacterium, F. prausnitzii (Fp-EVs), in inflammatory bowel disease (IBD) on dextran sulfate sodium (DSS)-induced colitis in mice.
Results
Fp-EVs isolated by ultracentrifugation and typically exhibited a double concave disc shape with an average diameter of 172 nm. Fp-EVs treatment reduced DSS-induced weight loss, disease activity index (DAI) score, colon length shortening, histological damage, neutrophil infiltration and increased intestinal epithelial apoptotic cells in DSS-induced colitis mice. Fp-EVs upregulated the protein expression of zona occludens (ZO)-1 and Occludin and increased the ratio of Tregs in the colon tissue of colitis mice. Furthermore, Fp-EVs downregulated the expression of the proinflammatory cytokines interleukin-1β (IL-1β), IL-2, IL-6, IL-12a, IL-17a, Interferon-γ (IFN-γ), tumor necrosis factor - α (TNF-α), granulocyte-macrophage colony stimulating factor (GM-CSF) and upregulated the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor β (TGF-β) in DSS-treated mice. Moreover, Fp-EV treatment markedly reduced the phosphorylation of these proteins Nuclear factor-κB (NF-κB) and Mitogen activated protein kinase (MAPK), and regulated the expression of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1).
Conclusion
Our findings revealed that Fp-EVs attenuated DSS-induced colitis by modulating the intestinal mucosal barrier function and immunological profile. Our findings reveal that Fp-EVs attenuate DSS-induced colitis by modulating intestinal mucosal barrier function and the immunological profile.
... Некоторые из них выполняют задачи, полезные для человека-хозяина, участвуя в формировании симбиотических или комменсальных взаимоотношений. Те микробы, которые рутинно при физиологических процессах жизнедеятельности не вызывают заболевания, считаются нормальной флорой или нормальной микробиотой [4]. Парадокс заключается в том, что современному научному сообществу до сих пор не совсем ясна роль и конкретные функции большинства микросообществ, несмотря на их видовое разнообразие и численное превосходство над клетками человеческого организма. ...
Introduction. The concept of microbiome is a collective term for many microorganisms, such as bacteria, archaea, fungi, protists, and viruses, inhabiting various anatomical areas of the human body. The relevance of studying their quantitative and qualitative relationships is associated with the size of microbial populations, as well as the lack of awareness of the modern scientific community about the true role of most of them, including the connection between the microbiome diversity of male testicles and sperm with the presence of azoospermia and the development of idiopathic variants of infertility. The purpose: identification of the composition of the microbiome of testicular tissue in infertile men and determination of its clinical significance. Studying the influence of microbial populations of the urogenital tract of men on the development and course of diseases associated with infertility, such as azoospermia. Materials and methods. A literature review was performed based on data published in the PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) and Scientific Electronic Library eLibrary.ru (https://elibrary.ru/) databases. The search was carried out using the following keywords: microbiome; microbiota; testicular tissue; azoospermia; sequencing; genome; male infertility. A total of 167 sources were analyzed. For this publication, 48 publications were selected. Results. Lactobacillus iners, Gardnerella vaginalis, Escherichia faecalis, Escherichia coli and Staphylococcus aureus are associated with the development of non-obstructive azoospermia. In men with different forms of azoospermia, a greater number of Bacteroidetes and Firmicutes phyla were observed, while Proteobacteria and Actinobacteria were significantly less common compared to healthy controls. Also, the microbial diversity between obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) had a higher degree of similarity than the control group. Interestingly, the microbiome modifications found in men with NOA are similar to those previously identified in the gut of older adults, which can be considered as further evidence of microbiologically early aging of NOA men at the testicular level. Conclusions. Microbiome analysis demonstrated for the first time that human testicular tissue is not a microbiologically sterile environment, and also provided new data on the bacteriological composition of the male urogenital tract and allowed us to consider excluding any potential contribution of microbial communities present in neighboring anatomical regions. Therefore, larger studies are needed to confirm our preliminary findings that the testes of azoospermic men contain a more dysbiotic bacterial community.
... The gastrointestinal system comprises of the mouth, esophagus, stomach, small intestine, large intestine, and anus. Inside the large intestine resides the gut microflora, containing about 400 anaerobic bacterial species (Quigley 2013). This microflora is sparse in the stomach and small intestine, but very apparent in the colon (large intestine). ...
... These approaches have given researchers previously unheard-of insights into the richness and makeup of the gut microbiota, enabling them to pinpoint specific microbial taxa and functional pathways linked to neurodegenerative diseases. For instance, research has shown that people with PD and AD have altered gut microbiotas, showing variations in the abundance of particular bacterial taxa and the possibility of metabolic pathway dysregulation [4,5]. It is possible that neurodegenerative diseases affect intestinal-innervating nerve cells and CNS neurons because they disrupt vital CNS processes as well as persistent gut dysfunctions. ...
Small microscopic entities known as microbes, having a population of hundreds of billions or perhaps even in trillions, reside in our gastrointestinal tract. A healthy immune system, digestion, and creation of vitamins and enzymes are all thanks to these microbes. However, new research has shown a hitherto unrecognized connection between the microbiota of the intestines and the genesis of neurodegenerative diseases. Neurons in the CNS gradually deteriorate in neurodegenerative illnesses like multiple sclerosis and Parkinson's disease (PD). This deterioration impairs cognitive and physical function. Amyotrophic lateral sclerosis (ALS), PD, and Alzheimer's disease (AD) are just a few examples of neurodegenerative illnesses that pose a serious threat to world health and have few effective treatments. Recent research suggests that the gut microbiota, a diverse microbial population found in the gastrointestinal system, may substantially impact the cause and development of various diseases. The discovery of altered gut microbiota composition in people with these illnesses is one of the most critical lines of evidence connecting gut microbiota dysbiosis to neurodegenerative diseases. AD patients have a distinct characteristic of having a particular microbiota profile. In addition, an excess population of a specific microbe data profile is seen as compared to a healthy individual. Similar changes in the gut microbiota composition have been noted in people with multiple sclerosis and PD. The latest study indicates the potential that dysbiosis, a condition characterized by alteration in the intestinal microbiota's makeup and functioning, may have an effect on the onset and progression of neurodegenerative diseases, including PD and multiple sclerosis. In order to emphasize any potential underlying mechanisms and examine potential treatment repercussions, the review article's goal is to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders. The review article aims to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders, highlighting potential underlying mechanisms and examining potential treatment repercussions.
... These microscopic inhabitants play a crucial role in maintaining our overall health and well-being. However, certain factors such as antibiotic usage, dietary changes, and stress can disturb the delicate balance of these microbial communities, leading to what is known as flora imbalance (Quigley, 2013). ...
Probiotics, beneficial bacteria with significant therapeutic potential, have gained attention for addressing a range of health issues, including gastrointestinal disorders, immune deficiencies, and mental health concerns. This article delves into the expression and purification of recombinant microbial enzymes to harness the therapeutic potential of probiotics. Probiotics offer promise in promoting overall well-being and preventing diseases through their ability to modulate immune responses and enhance gut health. They have proven effective in alleviating symptoms related to conditions like irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and antibiotic-associated diarrhea. These live microorganisms, when administered in sufficient quantities, restore gut flora balance and modulate immune responses. By engineering probiotics to produce therapeutic enzymes that aid digestion or regulate gut microbiota, they can significantly contribute to digestive health and mitigate IBS and IBD symptoms. The expression and purification of recombinant microbial enzymes play a crucial role in enhancing probiotics' therapeutic capabilities, enabling tailored treatments for various health challenges. In summary, probiotics represent a promising frontier in therapeutic microbiology and biotechnology. Their multifaceted benefits, when combined with recombinant microbial enzyme expression and purification, hold immense potential for advancing the field of therapeutic probiotics and improving human health.
... In support of this proposal, a previous study found that, compared with healthy controls, ME/CFS patients had abnormally high levels of IgA and IgM produced in response to a panel of seven gram-negative enterobacteria [13]. However, this small panel of microbes does not reflect the complexity of the intestinal microbiota which comprises 300-500 bacterial species as well as viruses, archaea and fungi [19]. In addition, IgM antibodies have low specificity for antigens [20] and IgA is primarily produced at mucosal sites [21]. ...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic disease of unknown aetiology that is characterised by disabling chronic fatigue and involves both the immune and gastrointestinal (GI) systems. Patients display alterations in GI microbiome with a significant proportion experiencing GI discomfort and pain and elevated blood biomarkers for altered intestinal permeability compared with healthy individuals. To investigate a possible GI origin of ME/CFS we designed a feasibility study to test the hypothesis that ME/CFS pathogenesis is a consequence of increased intestinal permeability that results in microbial translocation and a breakdown in immune tolerance leading to generation of antibodies reactive to indigenous intestinal microbes. Secretory immunoglobulin (Ig) A and serum IgG levels and reactivity to intestinal microbes were assessed in five pairs of severe ME/CFS patients and matched same-household healthy controls. For profiling serum IgG, we developed IgG-Seq which combines flow-cytometry based bacterial cell sorting and metagenomics to detect mucosal IgG reactivity to the microbiome. We uncovered evidence for immune dysfunction in severe ME/CFS patients that was characterised by reduced capacity and reactivity of serum IgG to stool microbes, irrespective of their source. This study provides the rationale for additional studies in larger cohorts of ME/CFS patients to further explore immune-microbiome interactions.
... The human gut microbiota is recognized as the largest microecosystem present in the human body. This microbial community is extremely complex and heterogeneous, composed of bacteria, archaea, fungi, and viruses that interact with each other and the human host in a symbiotic manner (1,2) . While the stomach harbors only a few bacteria, the colon contains approximately 300 to 1000 different species, explaining why up to 60% of the dry mass of feces is made up of bacteria (3) . ...
The human gut microbiota plays various essential roles, including protection against pathogens, intestinal function regulation, synthesis of compounds for the host, diet compound metabolism, and direct influence on host homeostasis. The composition of the microbiota is influenced by factors like diet, age, and lifestyle, with the Westernized culture being associated with harmfull imbalances. Disruption of the gut microbiota has been linked to various pathological processes, from intestinal syndromes to systemic conditions like allergies, insulin resistance, and neurological alterations. Microbiota disturbances can lead to cellular changes in colorectal tissue due to metabolic, genomic, and inflammatory influences. Therapeutic interventions to modulate the gut microbiota are considered promising approaches for managing and preventing these diseases. Continuous research on the gut microbiota and its relation to human health is of utmost importance to understand the underlying mechanisms and develop specific therapeutic interventions, complementing conventional treatment approaches.
... However, over time, the patient enters a second stage, which accompanies the infection and is another cause of the high mortality rate of SAP. 1 Studies have shown that most pancreatic and extra-pancreatic organ infections are caused by the translocation of intestinal bacteria; such infections result in pancreatic necrosis and sepsis, causing late death in patients with SAP. 2 The gut microbiota (GM) is mutualistic with the human body under certain steady states; some gut bacteria can ferment dietary fiber to form short-chain fatty acids (SCFAs), which are then absorbed by the host. 3 The intestinal mucosa can also maintain the stability of the intestinal environment through its barrier function. Once this stability is disrupted by a persistent inflammatory response in SAP, this can lead to intestinal mucosal damage and a change in the status of the intestinal microbiota. ...
Acute pancreatitis (AP) is one of the most common acute abdominal conditions, and its incidence has been increasing for years. Approximately 15–20% of patients develop severe AP (SAP), which is complicated by critical inflammatory injury and intestinal dysfunction. AP-associated inflammation can lead to the gut barrier and function damage, causing dysbacteriosis and facilitating intestinal microbiota migration. Pancreatic exocrine deficiency and decreased levels of antimicrobial peptides in AP can also lead to abnormal growth of intestinal bacteria. Meanwhile, intestinal microbiota migration influences the pancreatic microenvironment and affects the severity of AP, which, in turn, exacerbates the systemic inflammatory response. Thus, the interaction between the gut microbiota (GM) and the inflammatory response may be a key pathogenic feature of SAP. Treating either of these factors or breaking their interaction may offer some benefits for SAP treatment. In this review, we discuss the mechanisms of interaction of the GM and inflammation in AP and factors that can deteriorate or even cure both, including some traditional Chinese medicine treatments, to provide new methods for studying AP pathogenesis and developing therapies.
... The gut microbiota is a dynamic and diverse microbial community that resides in the digestive system, and it is the largest compared with other body sites [29]. The intestinal microbiota contains over 1500 species, mainly of the phyla Bacteroidetes and Firmicutes, which account for 90% of the gut microbial community [30]. ...
Rheumatic heart disease (RHD) represents a serious cardiac sequela of acute rheumatic fever, occurring in 30–45% of patients. RHD is multifactorial, with a strong familial predisposition and known environmental risk factors that drive loss of immunological tolerance. The gut and oral microbiome have recently been implicated in the pathogenesis of RHD. Disruption of the delicate balance of the microbiome, or dysbiosis, is thought to lead to autoimmune responses through several different mechanisms including molecular mimicry, epitope spreading, and bystander activation. However, data on the microbiomes of RHD patients are scarce. Therefore, in this comprehensive review, we explore the various dimensions of the intricate relationship between the microbiome and the immune system in RHD and other rheumatic diseases to explore the potential effect of microbiota on RHD and opportunities for diagnosis and treatment.
... At the genus level, we found that the association between the gut microbiota and the clinical indicators was more complex in all groups. It is thought that some bacteria may significantly affect human metabolism, although their abundance is low (Quigley, 2013). As in the case of Oscillibacter, although it was not considered a dominant genus in any groups in this study, it is noteworthy that it was somehow associated with glycemic or lipid indicators in each group. ...
Background
Clozapine is considered one of the most effective antipsychotic drugs, but it is most likely to cause metabolic abnormalities. Researchers have studied the causes of metabolic abnormalities caused by clozapine from multiple perspectives, but the reasons remain unclear.
Purpose
Characterize the gut microbiota of people with schizophrenia taking clozapine, exploring the association between gut microbiota and glucose lipid metabolic markers in schizophrenia patients taking clozapine.
Research design
Sixty-one long-term inpatients with schizophrenia in clozapine monotherapy were selected as study subjects. We got four subgroups by sex and the presence of metabolic syndrome.
Data analysis
16s analysis technology was applied at the genus level to determine the classification of gut microbiota. Then we compared the characteristics of gut microbiota and the association of gut microbiota with glucose lipid metabolic markers in each group.
Findings
We found differences in the diversity of gut microbiota among groups. The association between gut microbiota and glucose lipid metabolic markers was complicated. Gender was an important differentiating factor. Oscillibacter has a low abundance. However, it was the only genus associated with glycemic or lipids in each group. Among metabolic syndromes, Gemmiger was positively correlated with most lipids in females but negatively correlated in males, showing gender differences. In female non-metabolic syndromes, Bifidobacterium lost its probiotic character; instead, showing pathogenicity, which has strong positive correlations with fasting blood glucose and low-density lipoprotein but negative correlations with Apolipoprotein A1. Maybe schizophrenia, taking clozapine, and gender factors influenced the gut microbiota, which complicated our findings. The significance of the results remains to be determined by in-depth studies.
... Traditionally used dairy products are regarded as the main source of these probiotic strains (Kiani, Nami, Hedayati, Elieh Ali Komi, et al., 2021;Kiani, Nami, Hedayati, Jaymand, et al., 2021), while they can also be found in fermented and nonfermented food products, such as cereals, fruits, vegetables, meats, and fish (Damián et al., 2022;Zommiti et al., 2020). Gastrointestinal flora consists of approximately 300-500 bacterial species, whereat Bacteroides, Porphyromonas, Bifidobacterium, Lactobacillus, Enterococcus, and Clostridium have been recognized as the most dominant in human gastrointestinal tract (Quigley, 2013). The importance and application of probiotic strains are multiple considering that they possess proven therapeutic effects (Kiani, Nami, Hedayati, Elieh Ali Komi, et al., 2021;Kiani, Nami, Hedayati, Jaymand, et al., 2021). ...
Laetiporus sulphureus (Bull.) Murrill is a well-known edible mushroom consumed in nutrition as delicacy. It has been used in traditional medicine because of its beneficial effects on human wellness, such as antimicrobial, antioxidant, and anticancer potential. The present study determined the phenolic profile of Laetiporus sulphureus ethanolic extract (LSE) by high-performance liquid chromatographic method. Tolerance of two probiotic bacterial strains Lactiplantibacillus plantarum 229v, Bifidobacterium animalis subsp. lactis and probiotic yeast Saccharomyces boulardii on LSE was analyzed in terms of viability and biofilm formation. Effects of extract on colorectal (HCT-116) and cer-vical (HeLa) cancer cells viability was determined using MTT test in concentration range: 1-500 μg/mL after 24 and 72 h. Redox parameters (superoxide anion radicals, nitrites, and reduced glutathione) were evaluated using NBT, Griess, and GSH assays in the concentration range of 1-500 μg/mL after 24 and 72 h. Antimigratory activity was determined by wound healing method using selected concentrations of 10 and 50 μg/mL after 24 h. Untreated cells were considered as control. As control cell line, we used healthy fibroblasts (MRC-5). Our results demonstrated abundance of LSE in phenolics, with rosmarinic acid as the main component. LSE induced low tolerance of tested planktonic probiotic strains, with no affection on their ability to form biofilm. No significant cytotoxicity on tested cancer cells was observed, with prooxidative and antimigratory effects noticed. Extract exerted significant antimigratory activity on cancer cells without effect on planktonic and probiotic cultures in biofilm. These results indicate potential application of Laetiporus sulphureus ethanolic extract as natural protector of probiotics with prominent ability to suppress cancer cell motility. K E Y W O R D S antibiofilm activity, migration, mushroom, phenolic profile, probiotics 2 | JOVANOVIĆ et al.
... Humans are routinely exposed to SiO 2 NPs on a daily basis through various routes, including oral ingestion [5]. The main target of orally ingested SiO 2 NPs is the gastrointestinal tract [5], which is at the same time continuously exposed to noxious components, such as bacterial products [6]. In this study, we sought to understand the cell association with SiO 2 NPs in the presence of a bacterial virulent factor, e.g., cholera toxin subunit B (CTxB). ...
The gastrointestinal tract is the main target of orally ingested nanoparticles (NPs) and at the same time is exposed to noxious substances, such as bacterial components. We investigated the interaction of 59 nm silica (SiO2) NPs with differentiated Caco-2 intestinal epithelial cells in the presence of cholera toxin subunit B (CTxB) and compared the effects to J774A.1 macrophages. CTxB can affect cellular functions and modulate endocytosis via binding to the monosialoganglioside (GM1) receptor, expressed on both cell lines. After stimulating macrophages with CTxB, we observed notable changes in the membrane structure but not in Caco-2 cells, and no secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) was detected. Cells were then exposed to 59 nm SiO2 NPs and CtxB sequentially and simultaneously, resulting in a high NP uptake in J774A.1 cells, but no uptake in Caco-2 cells was detected. Flow cytometry analysis revealed that the exposure of J774A.1 cells to CTxB resulted in a significant reduction in the uptake of SiO2 NPs. In contrast, the uptake of NPs by highly selective Caco-2 cells remained unaffected following CTxB exposure. Based on colocalization studies, CTxB and NPs might enter cells via shared endocytic pathways, followed by their sorting into different intracellular compartments. Our findings provide new insights into CTxB’s function of modulating SiO2 NP uptake in phagocytic but not in differentiated intestine cells.
... The colonic region is a highly favourable environment for anaerobic bacteria, and it harbours the densest population of the gut microbiome, especially anaerobes [18]. The delivery of viable anaerobic bacteria to the colon by oral route is a challenge since there is a need to protect the bacterial cells from O 2 during manufacture, storage, and from the hostile conditions of the upper intestinal tract. ...
Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eu-dragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release , showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 10 6-10 7 CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.
... To put this into perspective, bacterial cell count is roughly estimated on a 1:1 scale with human cells, and genes from commensal microbes outnumber human genes 100 to 1 [1,2]. The gastrointestinal (GI) tract, arguably containing around 300+ bacterial species, houses a majority of the microorganisms and their genes, collectively referred to as the gut microbiome (GM) [1,3]. With a vast amount of highly diverse genetic material in the gut, this previously overlooked organ has gained significant attention for studying host-microbiome interactions and the impact of GM on human health and in pharmacological applications to drug development. ...
Background:
The gut microbiome is a diverse system within the gastrointestinal tract composed of trillions of microorganisms (gut microbiota), along with their genomes. Accumulated evidence has revealed the significance of the gut microbiome in human health and disease. Due to its ability to alter drug/xenobiotic pharmacokinetics and therapeutic outcomes, this once-forgotten "metabolic organ" is receiving increasing attention. In parallel with the growing microbiome-driven studies, traditional analytical techniques and technologies have also evolved, allowing researchers to gain a deeper understanding of the functional and mechanistic effects of gut microbiome.
Aim of review:
From a drug development perspective, microbial drug metabolism are becoming increasingly critical as new modalities (e.g., degradation peptides) with potential microbial metabolism implications emerge. The pharmaceutical industry thus has a pressing need to stay up-to-date with, and continue pursuing, research efforts investigating clinical impact of the gut microbiome on drug actions whilst integrating advances in analytical technology and gut microbiome models. Our review aims to practically address this need by comprehensively introducing the latest innovations in microbial drug metabolism research- including strengths and limitations, to aid in mechanistically dissecting the impact of the gut microbiome on drug metabolism and therapeutic impact, and to develop informed strategies to address microbiome-related drug liability and minimize clinical risk.
Key scientific concepts of review:
We present comprehensive mechanisms and co-contributing factors by which gut microbiome influences drug therapeutic outcomes. We highlight in vitro, in vivo, and in silico models for elucidating the mechanistic role and clinical impact of the gut microbiome on drugs in combination with high-throughput, functionally oriented, and physiologically relevant techniques. Integrating pharmaceutical knowledge and insight, we provide practical suggestions to pharmaceutical scientists for when, why, how, and what is next in microbial studies for improved drug efficacy and safety, and ultimately, support precision medicine formulation for personalized and efficacious therapies.
... The human gut hosts the largest number and species of bacteria compared to other human organs [187]. The Human Microbiome project revealed astronomical numbers (over 10 13 ) of resident gut bacteria [188], which may not be commensal, but are otherwise engaged in mutually beneficial relationships. ...
Insulin resistance (IR), accompanied by an impaired cellular glucose uptake, characterizes diverse pathologies that include, but are not limited to, metabolic disease, prediabetes and type 2 diabetes. Chronic inflammation associated with deranged cellular signaling is thought to contribute to IR. The key molecular players in IR are plasma membrane proteins, including the insulin receptor and glucose transporter 4. Certain natural products, such as lipids, phenols, terpenes, antibiotics and alkaloids have beneficial effects on IR, yet their mode of action remains obscured. We hypothesized that these products belong to a novel class of bioactive molecules that we have named membrane-active immunomodulators (MAIMs). A representative MAIM, the naturally occurring medium chain fatty acid ester diethyl azelate (DEA), has been shown to increase the fluidity of cell plasma membranes with subsequent downstream effects on cellular signaling. DEA has also been shown to improve markers of IR, including blood glucose, insulin and lipid levels, in humans. The literature supports the notion that DEA and other natural MAIMs share similar mechanisms of action in improving IR. These findings shed a new light on the mechanism of IR mitigation using natural products, and may facilitate the discovery of other compounds with similar activities.
... The human intestinal tract is a complex consortium of over 300 bacterial species and trillions of individual bacteria, which comprise the intestinal microbiota and form a unique ecosystem adapted to the intestinal environment (Quigley, 2013;Sender et al., 2016). The gut microbiome modulates gastrointestinal development, confers enhanced metabolic capabilities, and protects against pathogens (Bäckhed et al., 2005). ...
Legumes contain dietary fiber and resistant starch, which are beneficial to the intestinal environment. Here, we investigated the effects of yellow pea noodle consumption on the gut microbiota and fecal metabolome of healthy individuals. This single‐armed pre‐post comparative pilot study evaluated eight healthy female participants who consumed yellow pea noodles for 4 weeks. The gut microbiota composition and fecal metabolomic profile of each participant were evaluated before (2 weeks), during (4 weeks), and after (4 weeks) daily yellow pea noodle consumption. 16S rRNA gene sequencing was performed on stool samples, followed by clustering of operational taxonomic units using the Cluster Database at High Identity with Tolerance and integrated QIIME pipeline to elucidate the gut microbiota composition. The fecal metabolites were analyzed using capillary electrophoresis time‐of‐flight mass spectrometry and liquid chromatography time‐of‐flight mass spectrometry. Compared to day 0, the relative abundances of five bacterial genera ( Bacteroides, Bilophila, Hungatella, Parabacteroides , and Streptococcus ) in the intestinal microbiota significantly decreased, wherein those of Bifidobacterium longum and Ruminococcus bromii were increased on day 29 and decreased to the basal level (day 0) on day 57. Fecal metabolomic analysis identified 11 compounds showing significant fluctuations in participants on day 29 compared to day 0. Although the average levels of short‐chain fatty acids in participants did not differ significantly on day 29 compared to those on day 0, the levels tended to increase in individual participants with >8% relative abundance of R. bromii in their gut microbiota. In conclusion, incorporating yellow peas as a daily staple may confer human health benefits by favorably altering the intestinal environment.
... The intestinal microbiota consists of a complex community of microorganisms [30], including bacteria, viruses, and some eukaryotes that live in the digestive tracts of humans and animals [66]. The number of bacterial cells in the human intestinal microbiota is approximately 10 14 , which is 10 times higher than the number of human cells [67]. ...
Several epidemiologic studies have found that consuming fruits and vegetables lowers the risk of getting a variety of chronic illnesses, including several types of cancers, cardiovascular diseases (CVDs), and bowel diseases. Although there is still debate over the bioactive components, various secondary plant metabolites have been linked to these positive health benefits. Many of these features have recently been connected to carotenoids and their metabolites’ effects on intracellular signalling cascades, which influence gene expression and protein translation. Carotenoids are the most prevalent lipid-soluble phytochemicals in the human diet, are found in micromolar amounts in human serum, and are very susceptible to multiple oxidation and isomerisation reactions. The gastrointestinal delivery system, digestion processes, stability, and functionality of carotenoids, as well as their impact on the gut microbiota and how carotenoids may be effective modulators of oxidative stress and inflammatory pathways, are still lacking research advances. Although several pathways involved in carotenoids’ bioactivity have been identified, future studies should focus on the carotenoids’ relationships, related metabolites, and their effects on transcription factors and metabolism.
... Studies of gut microbiota and their correlation with diseases have been widely described in recent years. Changes in gut microbiota have been linked not to metabolism (Quigley et al. 2013), immunity (Kosiewicz et al. 2011) and liver damage (Sun et al. 2020) but also to the nervous and respiratory systems (Morais et al.2021;Chunxi et al. 2020) as well as chronic kidney disease (CKD) (Kim et al. 2021). Because of the underlying deterioration of the intestinal epithelium, impaired intestinal mucosal barrier and translocation of endogenous microorganisms, the gut is believed to be the driving factor that causes multiple infections in sepsis (Mittal et al. 2014). ...
The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.
... The gut is an important organ for stress after sepsis and other acute stressors [3]. Several illnesses like auto-immune, chronic liver disease, inflammatory bowel disease, and diabetes have been linked to alterations in the gut microbiome [4,5]. Dysbiosis is a common term used to indicate disorders of gut microbiota [6]. ...
Ventilator-associated pneumonia (VAP) is a nosocomial infection contracted by ventilator patients in which bacteria colonize the upper digestive tract and contaminated secretions are released into the lower airway. This nosocomial infection increases the morbidity and mortality of the patients as well as the cost of treatment. Probiotic formulations have recently been proposed to prevent the colonization of these pathogenic bacteria. In this prospective observational study, we aimed to investigate the effects of probiotics on gut microbiota and their relation to clinical outcomes in mechanically ventilated patients. For this study, 35 patients were recruited (22 probiotic-treated and 13 without probiotic treatment) from a cohort of 169 patients. Patients in the probiotic group were given a dose of 6 capsules of a commercially available probiotic (VSL#3®:112.5 billion CFU/cap) in three divided doses for 10 days. Sampling was carried out after each dose to monitor the temporal change in the gut microbiota composition. To profile the microbiota, we used a 16S rRNA metagenomic approach, and differences among the groups were computed using multivariate statistical analyses. Differences in gut microbial diversity (Bray Curtis and Jaccard distance, p-value > 0.05) between the probiotic-treated group and the control group were not observed. Furthermore, treatment with probiotics resulted in the enrichment of Lactobacillus and Streptococcus in the gut microbiota of the probiotic-treated groups. Our results demonstrated that probiotics might lead to favorable alterations in gut microbiome characteristics. Future studies should focus on the appropriate dosages and frequency of probiotics, which can lead to improved clinical outcomes.
... Bağırsak mikrobiyotası, insanların ve hayvanların sindirim kanallarında yaşayan karmaşık bir mikroorganizma topluluğudur. İnsanlarda, bağırsak mikrobiyotası vücudun diğer bölümlerine kıyasla en fazla sayıda ve türde mikroorganizmaya sahiptir (Quigley, 2013;Gomaa, 2020). Doğumdan hemen sonra sindirim sistemini kolonize eden bakteri, virüs ve bazı ökaryotlar dahil binlerce mikroorganizmadan oluşmaktadır (Passos ve Moraes-Filho, 2017; Gomaa, 2020). ...
... These microbial populations can not only protect the human body from foreign microorganisms and pathogens, but also participate in intestinal digestion and absorption, and promote metabolism (Guarner and Malagelada, 2003;Kau et al., 2011). Therefore, to some extent, the human microbial population can even be regarded as human "forgotten organs" (Quigley, 2013), the imbalance of microorganisms will not only lead to the occurrence of nervous system diseases, but also affect the immune and metabolic functions of the human body (Cenit et al., 2017;Li et al., 2017). For example, changes in intestinal microbiota are highly correlated with the pathogenesis of various nervous system diseases, including depression, autism (Kim et al., 2018), asthma (Al-Moamary et al., 2021) and cancer (Schwabe and Jobin, 2013), etc. ...
Researches have demonstrated that microorganisms are indispensable for the nutrition transportation, growth and development of human bodies, and disorder and imbalance of microbiota may lead to the occurrence of diseases. Therefore, it is crucial to study relationships between microbes and diseases. In this manuscript, we proposed a novel prediction model named MADGAN to infer potential microbe-disease associations by combining biological information of microbes and diseases with the generative adversarial networks. To our knowledge, it is the first attempt to use the generative adversarial network to complete this important task. In MADGAN, we firstly constructed different features for microbes and diseases based on multiple similarity metrics. And then, we further adopted graph convolution neural network (GCN) to derive different features for microbes and diseases automatically. Finally, we trained MADGAN to identify latent microbe-disease associations by games between the generation network and the decision network. Especially, in order to prevent over-smoothing during the model training process, we introduced the cross-level weight distribution structure to enhance the depth of the network based on the idea of residual network. Moreover, in order to validate the performance of MADGAN, we conducted comprehensive experiments and case studies based on databases of HMDAD and Disbiome respectively, and experimental results demonstrated that MADGAN not only achieved satisfactory prediction performances, but also outperformed existing state-of-the-art prediction models.
... The human gut microbiota is a community of microorganisms that includes viruses, bacteria, archeas, fungi and protozoa, and the microbiome is the collective genomes of microorganisms, their metabolites, and proteins in a specific environment (Budden et al., 2019). In humans, the intestine harbors the greatest number of microorganisms and the greatest number of species in relation to other places in the body (Quigley, 2013). They consist of over 1,500 species, which colonize the digestive tract within minutes of birth, establishing a symbiotic or mutualistic relationship with epithelial and lymphoid tissue (Robles-alonso et al., 2013;Horta-Baas et al., 2017;Lourido et al., 2017;Budden et al., 2019;Mitev and Taleski, 2019). ...
Thousands of microorganisms compose the human gut microbiota, fighting pathogens in infectious diseases and inhibiting or inducing inflammation in different immunological contexts. The gut microbiome is a dynamic and complex ecosystem that helps in the proliferation, growth, and differentiation of epithelial and immune cells to maintain intestinal homeostasis. Disorders that cause alteration of this microbiota lead to an imbalance in the host’s immune regulation. Growing evidence supports that the gut microbial community is associated with the development and progression of different infectious and inflammatory diseases. Therefore, understanding the interaction between intestinal microbiota and the modulation of the host’s immune system is fundamental to understanding the mechanisms involved in different pathologies, as well as for the search of new treatments. Here we review the main gut bacteria capable of impacting the immune response in different pathologies and we discuss the mechanisms by which this interaction between the immune system and the microbiota can alter disease outcomes.
... It could be speculated that antimicrobial substances produced by LAB, such as bacteriocins [6,7], organic acids [8], hydrogen peroxide [9] and diacetyl [10], can promote host health, (i.e., inhibiting the colonization of pathogenic microorganisms). Increasing evidence suggested that changes in the composition of microbial community increase the susceptibility to pathogens invasion [66]. Therefore, the high proportion of potential pathogens could be the sign of the intestinal microbiota instability, resulting in the high cumulative mortality of shrimp in the CO group. ...
The present study evaluated the growth performance, immune responses, disease resistance and intestinal microbiota in Penaeus vannamei fed diets supplemented with three strains of lactic acid bacteria (LAB). The basal diet (control, CO) supplemented with Lactobacillus plantarum W2 (LA), Pediococcus acidilactici Nj (PE), Enterococcus faecium LYB (EN) and florfenicol (FL), respectively, formed three LAB diets (1 × 1010 cfu kg-1) and a florfenicol diet (15 mg kg-1, positive control), were fed to shrimp for 42 days. Results indicated that specific growth rate, feed efficiency rate, and disease resistance of shrimp against Vibrio parahaemolyticus in the treatment groups were significantly improved versus the control (P < 0.05). Compared with the control, acid phosphatase, alkaline phosphatase, phenonoloxidase, total nitric oxide synthase, peroxidase, superoxide dismutase activities, total antioxidant capacity, and lysozyme content in the serum and the relative expression levels of SOD, LZM, proPO, LGBP, HSP70, Imd, Toll, Relish, TOR, 4E-BP, eIF4E1α and eIF4E2 genes in the hepatopancreas of LAB groups were enhanced to various extents. Intestinal microbiota analysis showed that the LA and EN groups significantly improved microbial diversity and richness, and LAB groups significantly altered intestinal microbial structure of shrimp. At the phylum level, the Verrucomicrobiota in the LA and PE groups, the Firmicutes in the EN group, and the Actinobacteriota in the PE and EN groups were enriched. Moreover, the CO group increased the proportion of potential pathogens (Vibrionaceae and Flavobacteriaceae). The potential pathogen (Vibrio) was reduced, and potential beneficial bacteria (Tenacibaculum, Ruegeria and Bdellovibrio) were enriched in response to dietary three strains of LAB. When the intestinal microbiota homeostasis of shrimp is considered, L. plantarum and E. faecium showed better effects than P. acidilactici. However, due to the concerns on the possible potential risks of E. faecium strains to human health, L. plantarum W2 is more suitable for application in aquaculture than E. faecium LYB. Considering collectively the above, Lactobacillus plantarum W2 could be applied as better probiotic to improve the growth performance, non-specific immunity, disease resistance and promote intestinal health of P. vannamei.
... The relationship between gut flora and humans is not only symbiotic (harmless coexistence), but also reciprocal. Some human gut florae benefit the host by fermenting dietary fiber into short chain fatty acids (SCFAs) [13][14][15]. It has been proven that the imbalance of the gut flora will bring many diseases to humans. ...
There is a symbiotic relationship between gut microbiota and human beings. Imbalance of the gut microbiota will cause pathological damages to humans. Although many risk factors are associated with missed abortion (MA), the pathological mechanism of it is still unclear. Here, we analyzed gut flora of the patients with MA by S16 high-throughput sequencing. The possible pathogenic mechanisms of the MA were explored. Fecal samples from 14 healthy controls and 16 MA patients were collected to do 16S rRNA gene high-throughput sequencing analysis. The abundance of the Bacteroidetes , Proteobacteria , Actinobacteria , Escherichia , Streptococcus_ Salivarius , and Lactobacillus was significantly reduced in the MA group, while, the abundance of the Klebsiella was significantly increased in the MA patients. The Ruminococcaceae and [Eubacterium]_coprostanoligenes_group were found only in the specimens of the MA patients. The Fabrotax function prediction analysis showed that four photosynthesis function bacteria ( cyanobateria , oxygenic_photoautotrophy , photoautotrophy , and phototrophy ) only existed in the MA group. In the analysis of the BugBase microbiome function prediction, the Escherichia of the MA group is significantly reduced compared to that of the healthy controls in the items of that Contains_Mobile_Elements , Facultatively_Anaerobic , Forms_Biofilms , Potentially_Pathogenic.png , Gram_Nagative , and Stress_Tolerant_relabundance . These alterations may affect the stability of the host's immune, neural, metabolic and other systems by interfering with the balance of the gut microbiota or by the metabolites of those bacteria, causing the MA. This study explored the possible pathogenic factors of the gut microbiota of the MA. The results provide evidence to figure out the pathogenesis of the MA.
Background
Observational research has shed light on the ability of gut microbes to influence the onset and progression of gastrointestinal diseases. The causal relationships between specific gut microbiomes and various gastrointestinal conditions, however, remain unknown.
Methods
We investigated the relationship between gut microbiota and seven specific gastrointestinal disorders using a robust two‐sample Mendelian randomization (MR) approach. The inverse variance‐weighted (IVW) method was used as the primary analysis tool in our study. Furthermore, we conducted multiple sensitivity analyses to strengthen the robustness of our findings and ensure the reliability of the IVW method.
Results
Our research has discovered significant links between the composition of gut microbiota and a variety of gastrointestinal ailments. We found compelling links between 13 gut microbiota and fatty liver, four gut microbiota and cirrhosis, eight gut microbiota and hepatocellular carcinoma, four gut microbiota and cholelithiasis, 12 gut microbiota and acute pancreatitis, eight gut microbiota and chronic pancreatitis, and 11 gut microbiota and pancreatic cancer. These findings shed light on the intricate relationship between gut microbes and the emergence of these specific gastrointestinal conditions.
Conclusions
The findings of this extensive study not only validate the potential role of specific gut microbiota in gastrointestinal diseases, but also fill a critical gap in previous research. The discovery of these specific gut microbiota is a significant step forward because they may serve as novel and promising biomarkers for both the prevention and treatment of gastrointestinal conditions.
Hypertension is a frequent comorbidity in patients with heart failure; therefore, blood pressure management for these patients is widely recommended in medical guidelines. Bee pollen and postbiotics that contain inactivated probiotic cells and their metabolites have emerged as promising bioactive compounds sources, and their potential role in mitigating cardiovascular (CV) risks is currently being unveiled. Therefore, this preliminary study aimed to investigate the impact of a lactic-fermented bee pollen postbiotic (FBPP) on the CV microbiota via in vitro tests. A new isolated Lactobacillus spp. strain from the digestive tract of bees was used to ferment pollen, obtaining liquid and dried atomized caps postbiotics. The modulating effects on a CV microbiota that corresponds to the pathophysiology of hypertension were investigated using microbiological methods and qPCR and correlated with the metabolic profile. Both liquid and dried FBPPs increased the number of the beneficial Lactobacillus spp. and Bifidobacterium spp. bacteria by up to 2 log/mL, while the opportunistic pathogen E. coli, which contributes to CV pathogenesis, decreased by 3 log/mL. The short-chain fatty acid (SCFA) profile revealed a significant increase in lactic (6.386 ± 0.106 g/L) and acetic (4.284 ± 0.017 g/L) acids, both with known antihypertensive effects, and the presence of isovaleric acid, which promotes a healthy gut microbiota. Understanding the impact of the FBPP on gut microbiota could lead to innovative strategies for promoting heart health and preventing cardiovascular diseases.
Irritable bowel syndrome (IBS) is a prevalent gastrointestinal (GI) tract disorder. Although the main reason for IBS is not clear, the interaction between intestinal microorganisms and the gut barrier seems to play an important role in pathogenesis of IBS. The current study aimed to investigate the effect of Blastocystis on the gut microbiota profile and the circulation levels of microRNA (mir)-16 of IBS patients compared to healthy subjects. Stool and blood samples were collected from 80 participants including 40 samples from each IBS and healthy group. Upon DNA extraction from stool samples, barcoding region and quantitative real-time PCR were analyzed to investigate Blastocystis and the microbiota profile, respectively. RNA was extracted from serum samples of included subjects and the expression of mir-16 was evaluated using stem-loop protocol and qreal-time PCR. Significant changes between IBS patients and healthy controls was observed in Firmicutes, Actinobacteria, Faecalibacterium, and Alistipes. In IBS patients, the relative abundance of Bifidobacteria was directly correlated with the presence of Blastocystis, while Alistipes was decreased with Blastocystis. Lactobacillus was significantly increased in Blastocystis carriers. In healthy subjects, the relative abundance of Bifidobacteria was decreased, but Alistipes was increased in Blastocystis carriers. The changes in the Firmicutes/Bacteroidetes ratio was not significant in different groups. The relative expression of mir-16 in Blastocystis-negative IBS patients and healthy carriers was significantly overexpressed compared to control group. The presence of Blastocystis, decreased the relative expression of mir-16 in IBS patients compared to Blastocystis-negative IBS patients. The present study revealed that Blastocystis has the ability to change the abundance of some phyla/genera of bacteria in IBS and healthy subjects. Moreover, Blastocystis seems to modulate the relative expression of microRNAs to control the gut atmosphere, apply its pathogenicity, and provide a favor niche for its colonization.
Word Count: 8986 Highlights • Chichester Harbour is exposed to a variety of pollutants from agriculture and sewage • Mussels were exposed to Chichester harbour via transplantation as a bioindicator • After 14 days mussels had increased gonad size and gametogenesis • It can be inferred that endocrine disrupting pollutants triggered these effects Layperson's summary Water around the world is becoming ever more polluted due to its economical relevance in a variety of industries, often being the site where waste products build up or are disposed. This affects not only on humans, but over 1 million aquatic species. It has been known for a long time that pollution is dangerous for the environment, however, only recently have studies identified their adverse impacts. Our aim was to observe the potential effect of pollutants on mussels in Chichester Harbour to aid our understanding of how pollutants work, their effect on mussels and their wider impact on aquatic populations. To measure this, mussels were exposed to the polluted Chichester Harbour for 14 days and compared to mussels kept in pollution free containers. The group exposed to Chichester Harbour was shown to have increased sexual tissue growth, which was most likely due to the pollutant levels. Discussion of the specific pollutants which could cause these effects are presented. This impacts research by showing the effects of a specific habitat on mussels, proposing several studies which could be used for further research. Abstract (150-word journal limit) Water pollution poses a major threat to aquatic life in the UK, with anthropogenic agricultural runoff and sewage waste being major contributors. Exogenous pollutants have potential to persist inside aquatic environments and build up inside organisms' tissues, however, localised area specific effects are still relatively unknown. Here we utilised a transplantation study to evaluate the impact of pollution in Chichester Harbour, UK, on blue mussel gonads. The exposure group was maintained in Chichester Harbour for 14 days whilst the control group was kept in sterile seawater. ImageJ and statistical analysis suggested that mussel gonad surface area (μm 2) was significantly larger when exposed to pollutants in Chichester Harbour, and light microscopy also observed higher rates of gametogenesis. Our results suggested a prevalence of endocrine disrupting chemicals in the harbour, originating from a variety of sources which interfered with the hypothalamic-pituitary-gonadal axis, by mimicking or providing steroid hormones such as oestrogen.
Word Count: 8986 Highlights • Chichester Harbour is exposed to a variety of pollutants from agriculture and sewage • Mussels were exposed to Chichester harbour via transplantation as a bioindicator • After 14 days mussels had increased gonad size and gametogenesis • It can be inferred that endocrine disrupting pollutants triggered these effects Layperson's summary Water around the world is becoming ever more polluted due to its economical relevance in a variety of industries, often being the site where waste products build up or are disposed. This affects not only on humans, but over 1 million aquatic species. It has been known for a long time that pollution is dangerous for the environment, however, only recently have studies identified their adverse impacts. Our aim was to observe the potential effect of pollutants on mussels in Chichester Harbour to aid our understanding of how pollutants work, their effect on mussels and their wider impact on aquatic populations. To measure this, mussels were exposed to the polluted Chichester Harbour for 14 days and compared to mussels kept in pollution free containers. The group exposed to Chichester Harbour was shown to have increased sexual tissue growth, which was most likely due to the pollutant levels. Discussion of the specific pollutants which could cause these effects are presented. This impacts research by showing the effects of a specific habitat on mussels, proposing several studies which could be used for further research. Abstract (150-word journal limit) Water pollution poses a major threat to aquatic life in the UK, with anthropogenic agricultural runoff and sewage waste being major contributors. Exogenous pollutants have potential to persist inside aquatic environments and build up inside organisms' tissues, however, localised area specific effects are still relatively unknown. Here we utilised a transplantation study to evaluate the impact of pollution in Chichester Harbour, UK, on blue mussel gonads. The exposure group was maintained in Chichester Harbour for 14 days whilst the control group was kept in sterile seawater. ImageJ and statistical analysis suggested that mussel gonad surface area (μm 2) was significantly larger when exposed to pollutants in Chichester Harbour, and light microscopy also observed higher rates of gametogenesis. Our results suggested a prevalence of endocrine disrupting chemicals in the harbour, originating from a variety of sources which interfered with the hypothalamic-pituitary-gonadal axis, by mimicking or providing steroid hormones such as oestrogen.
The importance of bacterial microbiota on host metabolism and obesity risk is well documented. However, the role of fungal microbiota on host storage metabolite pools is largely unexplored. We aimed to investigate the role of microbiota on D . melanogaster fat metabolism, and examine interrelatedness between fungal and bacterial microbiota, and major metabolic pools. Fungal and bacterial microbiota profiles, fat, glycogen, and trehalose metabolic pools are measured in a context of genetic variation represented by whole genome sequenced inbred Drosophila Genetic Reference Panel (DGRP) samples. Increasing Basidiomycota, Acetobacter persici , Acetobacter pomorum , and Lactobacillus brevis levels correlated with decreasing triglyceride levels. Host genes and biological pathways, identified via genome-wide scans, associated with Basidiomycota and triglyceride levels were different suggesting the effect of Basidiomycota on fat metabolism is independent of host biological pathways that control fungal microbiota or host fat metabolism. Although triglyceride, glycogen and trehalose levels were highly correlated, microorganisms’ effect on triglyceride pool were independent of glycogen and trehalose levels. Multivariate analyses suggested positive interactions between Basidiomycota, A. persici , and L . brevis that collectively correlated negatively with fat and glycogen pools. In conclusion, fungal microbiota can be a major player in host fat metabolism. Interactions between fungal and bacterial microbiota may exert substantial control over host storage metabolite pools and influence obesity risk.
Colorectal cancer (CRC) is one of the leading causes of death in the United States and worldwide. Recent evidence has corroborated a strong correlation between poor diet and the development of CRC, and further research is being conducted to investigate the association between intestinal microbiome and the development of cancer. New studies have established links with certain foods and synthetic food compounds that may be effective in reducing the risk for carcinogenesis by providing protection against cancer cell proliferation and antagonizing oncogenic pathways. Prebiotics are gaining popularity as studies have demonstrated chemo-preventive as well as anticancer potential of prebiotics. This paper aims to discuss the wide definition and scope of prebiotics by reviewing the studies that provide insights into their effects on human health in the context of colorectal cancer.
Antibiotic-induced gut microbiome dysbiosis (AID) is known to be influenced by host dietary composition. However, how and when diet modulates gut dysbiosis remains poorly characterized. Thus, here, we utilize a multi-omics approach to characterize how a diet supplemented with oats, a rich source of microbiota-accessible carbohydrates, or dextrose impacts amoxicillin-induced changes to gut microbiome structure and transcriptional activity. We demonstrate that oat administration during amoxicillin challenge provides greater protection from AID than the always oats or recovery oats diet groups. In particular, the group in which oats were provided at the time of antibiotic exposure induced the greatest protection against AID while the other oat diets saw greater effects after amoxicillin challenge. The oat diets likewise reduced amoxicillin-driven elimination of Firmicutes compared to the dextrose diet. Functionally, gut communities fed dextrose were carbohydrate starved and favored respiratory metabolism and consequent metabolic stress management while oat-fed communities shifted their transcriptomic profile and emphasized antibiotic stress management. The metabolic trends were exemplified when assessing transcriptional activity of the following two common gut commensal bacteria: Akkermansia muciniphila and Bacteroides thetaiotaomicron. These findings demonstrate that while host diet is important in shaping how antibiotics effect the gut microbiome composition and function, diet timing may play an even greater role in dietary intervention-based therapeutics. IMPORTANCE We utilize a multi-omics approach to demonstrate that diets supplemented with oats, a rich source of microbiota-accessible carbohydrates, are able to confer protection against antibiotic-induced dysbiosis (AID). Our findings affirm that not only is host diet important in shaping antibiotics effects on gut microbiome composition and function but also that the timing of these diets may play an even greater role in managing AID. This work provides a nuanced perspective on dietary intervention against AID and may be informative on preventing AID during routine antibiotic treatment.
In recent years increasing evidence suggests that commensal microbiota may play an important role in health and disease, including cerebrovascular disease. Gut microbes impact physiology, at least in part by metabolizing dietary factors and also host-derived substrates and then generating active compounds including toxins. The purpose of the current review is to highlight the complex interplay between microbiota, their metabolites and essential functions for human health ranging from regulation of the metabolism and the immune system to modulation of brain development and function. We also discuss the role of gut dysbiosis in cerebrovascular disease, specifically in acute and chronic stroke phases and the possible implication of intestinal microbiota in post-stroke cognitive impairment and dementia, and we identify potential therapeutic opportunities of targeting microbiota in this context.
This part of the review focuses on the proposed involvement of the gut microbiota in the realization of the genetic risk of multiple sclerosis, the formation of the intestinal microbiome in early life, and provides data supporting the hypothesis that aberrant formation of the intestinal microbiota in early life may be a predisposing factor to multiple sclerosis.
Introduction:
As a chronic encephalopathy, drug addiction is responsible for millions of deaths per year around the world. The gut microbiome is a crucial component of the human microbiome. Through dynamic bidirectional communication along the 'gut-brain axis,' gut bacteria cooperate with their hosts to regulate the development and function of the immune, metabolic, and nervous systems.
Method:
These processes may affect human health because some brain diseases are related to the composition of gut bacteria, and disruptions in microbial communities have been implicated in neurological disorders.
Result:
We review the compositional and functional diversity of the gut microbiome in drug addiction. We discuss intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems and possible contributions by the gut microbiota to neurological disorders.
Conclusion:
Finally, the treatment of probiotics and fecal transplantation was summarized. This was done to further understand the role of intestinal microecology in the pathogenesis of drug addiction and to explore new methods for the treatment of drug addiction.
The microbiota-gut-brain axis (MGBA) has been the subject of much research over the past decade, offering an exciting new paradigm for the treatment of psychiatric disorders. In this review, the MGBA is extended to include skeletal muscle and the potential role of an expanded "muscle-gut-brain axis" (MuGBA) in conditions such as anxiety and depression is discussed. There is evidence, from both preclinical and human studies, of bidirectional links between the gut microbiome and skeletal muscle function and structure. The therapeutic role of exercise in reducing depressive and anxiety symptoms is widely recognised, and the potential role of the gut microbiota-skeletal muscle link is discussed within this context. Potential pathways of communication involved in the MuGBA including the tryptophan-kynurenine pathway, intestinal permeability, immune modulation, and bacterial metabolites such as short-chain-fatty-acids are explored.
Introduction: Billions of microorganisms reside in gut altering its homeostasis and leading to various diseases. The initial days of life are crucial for developing gut flora that helps in gut maturation and neonatal health. This review summarizes the evidence on seeding of neonatal gut microbiota, modulation of gut microbiota in neonatal sepsis, antimicrobial resistance, and role of probiotics or other therapies to re-establish altered microbiota. Conclusion: Gut microbiota regulates host physiological homeostasis mediators, including the gut barrier function, and disease susceptibility pathways. Maintenance or restoration of microbiota and metabolite composition may be a therapeutic or preventative target against critical illness.
One hypothesis for the etiology of inflammatory bowel disease is that an altered or pathogenic microbiota causes inflammation in a genetically susceptible individual. Understanding the microbiota's role in the pathogenesis of the disease could lead to new IBD treatments aimed at shifting the bacteria in the gut back to eubiosis. Probiotics have some efficacy in the treatment of ulcerative colitis (UC), but our current repertoire is limited in potency. Fecal microbiota therapy (FMT) is an emerging treatment for several gastrointestinal and metabolic disorders. It has demonstrated efficacy in treating refractory Clostridium difficile infection, and there are case reports of FMT successfully treating UC. Further clinical studies are justified, and could be complemented by mouse models of fecal transplantation, in which variables can be controlled and manipulated.
The literature on post-infectious irritable bowel syndrome (IBS) is reviewed with special emphasis on recent new data. Further accounts of this phenomenon continue to be reported following a range of infections including giardiasis as well as viral and bacterial gastroenteritis. Risk factors such as severity of initial illness, female gender together with adverse psychological factors have been confirmed. Recent evidence of a genetic predisposition needs replication. Animal studies suggest activation of mast cells and inflammation driven impairment of serotonin transporter may be important, which are findings supported by some recent human studies in IBS with diarrhoea. Experimentally induced inflammation leads to damage and remodelling of enteric nerves. Similar changes have been reported in IBS patients with increase in nerves expressing transient receptor potential cation channel V1. While changes in microbiota are very likely this area has yet to be explored using modern techniques. Since the prognosis is for slow improvement, treatments should currently target the key symptoms of diarrhoea and abdominal pain. Future therapies aimed at correcting underlying mechanisms including immune activation and serotonin excess are currently being explored and may provide better treatments in the future.
Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing.
Progress in the understanding of the pathophysiology of irritable bowel syndrome (IBS), once thought to be a purely psychosomatic disease, has advanced considerably and low-grade inflammation and changes in the gut microbiota now feature as potentially important. The human gut harbours a huge microbial ecosystem, which is equipped to perform a variety of functions such as digestion of food, metabolism of drugs, detoxification of toxic compounds, production of essential vitamins, prevention of attachment of pathogenic bacteria to the gut wall, and maintenance of homeostasis in the gastrointestinal tract. A subset of patients with IBS may have a quantitative increase in bacteria in the small bowel (small intestinal bacterial overgrowth). Qualitative changes in gut microbiota have also been associated with IBS. Targeting the gut microbiota using probiotics and antibiotics has emerged as a potentially effective approach to the treatment of this, hitherto enigmatic, functional bowel disorder. The gut microbiota in health, quantitative and qualitative microbiota changes, and therapeutic manipulations targeting the microbiota in patients with IBS are reviewed in this paper.
The colonization, development and maturation of the newborn gastrointestinal tract that begins immediately at birth and continues for two years, is modulated by numerous factors including mode of delivery, feeding regime, maternal diet/weight, probiotic and prebiotic use and antibiotic exposure pre-, peri- and post-natally. While in the past, culture-based approaches were used to assess the impact of these factors on the gut microbiota, these have now largely been replaced by culture-independent DNA-based approaches and most recently, high-throughput sequencing-based forms thereof. The aim of this review is to summarize recent research into the modulatory factors that impact on the acquisition and development of the infant gut microbiota, to outline the knowledge recently gained through the use of culture-independent techniques and, in particular, highlight advances in high-throughput sequencing and how these technologies have, and will continue to, fill gaps in our knowledge with respect to the human intestinal microbiota.
There is increasing interest in the administration of microbes or microbial metabolites for the prevention and treatment of aberrant inflammatory activity. The protective effects associated with these microbes are mediated by multiple mechanisms involving epithelial cells, DCs and T cells, but most data are derived from animal models. In this addendum, we summarize our recent data, showing that oral consumption of Bifidobacterium infantis 35624 is associated with enhanced IL-10 secretion and Foxp3 expression in human peripheral blood. In addition, we discuss the potential DC subset-specific mechanisms, which could contribute to DC(REG) and T(REG) programming by specific gut microbes.
The gut microbiota is a complex ecosystem that has a symbiotic relationship with its host. An association between the gut microbiota and disease was first postulated in the early 20(th) century. However, until the 1990s, knowledge of the gut microbiota was limited because bacteriological culture was the only technique available to characterize its composition. Only a fraction (estimated at <30%) of the gut microbiota has been cultured to date. Since the 1990s, advances in culture-independent techniques have spearheaded our knowledge of the complexity of this ecosystem. These techniques have elucidated the microbial diversity of the gut microbiota and have shown that alterations in the gut microbiota composition and function are associated with certain disease states, such as IBD and obesity. These new techniques are fast, facilitate high throughput, identify organisms that are uncultured to date and enable enumeration of organisms present in the gut microbiota. This Review discusses the techniques that can used to characterize the gut microbiota, when they can be applied to human studies and their relative advantages and limitations.
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.
Intestinal homoeostasis is dependent on immunological tolerance to the microbiota.
To (1) determine if a probiotic could induce Foxp3 T cells in humans; (2) to elucidate the molecular mechanisms, which are involved in the induction of Foxp3 T cells by human dendritic cells.
Cytokine secretion and Foxp3 expression were assessed in human volunteers following Bifidobacterium infantis feeding. Monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) were incubated in vitro with B. infantis and autologous lymphocytes. Transcription factor expression, costimulatory molecule expression, cytokine secretion, retinoic acid and tryptophan metabolism were analysed.
Volunteers fed B. infantis displayed a selective increase in secretion of interleukin (IL)-10 and enhanced Foxp3 expression in peripheral blood. In vitro, MDDCs, mDCs and pDCs expressed indoleamine 2,3-dioxygenase and secreted IL-10, but not IL-12p70, in response to B. infantis. MDDC and mDC IL-10 secretion was Toll-like receptor (TLR)-2/6 dependent, while pDC IL-10 secretion was TLR-9 dependent. In addition, MDDCs and mDCs expressed RALDH2, which was TLR-2 and DC-SIGN dependent. B. infantis-stimulated MDDCs, mDCs and pDCs induced T cell Foxp3 expression. TLR-2, DC-SIGN and retinoic acid were required for MDDC and mDC induction of Foxp3 T cells, while pDCs required indoleamine 2,3-dioxygenase.
B. infantis administration to humans selectively promotes immunoregulatory responses, suggesting that this microbe may have therapeutic utility in patients with inflammatory disease. Cross-talk between multiple pattern-recognition receptors and metabolic pathways determines the innate and subsequent T regulatory cell response to B. infantis. These findings link nutrition, microbiota and the induction of tolerance within the gastrointestinal mucosa.
There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
The genomes of four Lactobacillus reuteri strains isolated from human breast milk and the gastrointestinal tract have been recently sequenced as part of the Human Microbiome Project. Preliminary genome comparisons suggested that these strains belong to two different clades, previously shown to differ with respect to antimicrobial production, biofilm formation, and immunomodulation. To explain possible mechanisms of survival in the host and probiosis, we completed a detailed genomic comparison of two breast milk-derived isolates representative of each group: an established probiotic strain (L. reuteri ATCC 55730) and a strain with promising probiotic features (L. reuteri ATCC PTA 6475). Transcriptomes of L. reuteri strains in different growth phases were monitored using strain-specific microarrays, and compared using a pan-metabolic model representing all known metabolic reactions present in these strains. Both strains contained candidate genes involved in the survival and persistence in the gut such as mucus-binding proteins and enzymes scavenging reactive oxygen species. A large operon predicted to encode the synthesis of an exopolysaccharide was identified in strain 55730. Both strains were predicted to produce health-promoting factors, including antimicrobial agents and vitamins (folate, vitamin B(12)). Additionally, a complete pathway for thiamine biosynthesis was predicted in strain 55730 for the first time in this species. Candidate genes responsible for immunomodulatory properties of each strain were identified by transcriptomic comparisons. The production of bioactive metabolites by human-derived probiotics may be predicted using metabolic modeling and transcriptomics. Such strategies may facilitate selection and optimization of probiotics for health promotion, disease prevention and amelioration.
Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.
Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
While our current knowledge of probiotic interaction in the developing gut remains poorly understood, emerging science is providing greater biological insight into their mechanism of action and therapeutic potential for human disease. Given their beneficial effects, probiotics remain promising agents in neonatal gastrointestinal disorders. Probiotics may restore or supply essential bacterial strains needed for gut maturation and homeostasis, particularly in hosts where this process has been disrupted. Here we highlight the unique characteristics of developing intestinal epithelia with a focus on gut development and colonization as well as the inflammatory propensity of immature epithelia. Additionally, we review potential mechanisms of beneficial probiotic interaction with immature intestinal epithelia including immunomodulation, upregulation of cytoprotective genes, prevention and regulation of apoptosis and maintenance of barrier function. Improved knowledge of gut-probiotic interaction in developing epithelia will allow for a better understanding of how probiotics exert their beneficial effects and help guide their therapeutic use.
The intestinal microbiota includes a diverse group of functional microorganisms, including candidate probiotics or viable microorganisms that benefit the host. Beneficial effects of probiotics include enhancing intestinal epithelial cell function, protecting against physiologic stress, modulating cytokine secretion profiles, influencing T-lymphocyte populations, and enhancing antibody secretion. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects remain to be fully elucidated. Accumulating evidence demonstrates that probiotics communicate with the host by modulating key signaling pathways, such as NFκB and MAPK, to either enhance or suppress activation and influence downstream pathways. Beneficial microbes can profoundly alter the physiology of the gastrointestinal tract, and understanding these mechanisms may result in new diagnostic and therapeutic strategies.
Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
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.).
Important metabolic functions have been identified for the gut microbiota in health and disease. Several lines of evidence suggest a role for the gut microbiota in both the etiology of nonalcoholic fatty liver disease (NAFLD) and progression to its more advanced state, nonalcoholic steatohepatitis (NASH). Both NAFLD and NASH are strongly linked to obesity, type 2 diabetes mellitus and the metabolic syndrome and, accordingly, have become common worldwide problems. Small intestinal bacterial overgrowth of Gram-negative organisms could promote insulin resistance, increase endogenous ethanol production and induce choline deficiency, all factors implicated in NAFLD. Among the potential mediators of this association, lipopolysaccharide (a component of Gram-negative bacterial cell walls) exerts relevant metabolic and proinflammatory effects. Although the best evidence to support a role for the gut microbiota in NAFLD and NASH comes largely from animal models, data from studies in humans (albeit at times contradictory) is accumulating and could lead to new therapeutic avenues for these highly prevalent conditions.
We recently demonstrated that antibiotic administration has a reproducible effect on the community structure of the indigenous gastrointestinal microbiota of mice. In this addendum we report on additional experimentation using the antibiotic vancomycin. In accord with our previous findings, vancomycin administration results in consistent alteration of the microbiota of the cecal contents and the cecal mucosa. These alterations are largely reversed by a three-week period of recovery without antibiotics. In contrast to our previous results using other antibiotics, the alterations in community structure associated with vancomycin occured without a significant decrease in the overall bacterial biomass. These results indicate that different antibiotics have specific effects on the gut microbiota. This points the way towards targeted, therapeutic alteration of the gut bacterial community as a whole.
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.
Gut commensals modulate host immune, endocrine, and metabolic functions. They also affect peripheral and central neural reflexes and function. We have previously shown that daily ingestion of Lactobacillus reuteri (LR) for 9 d inhibits the pseudoaffective cardiac response and spinal single-fiber discharge evoked by visceral distension, and decreases intestinal motility and myenteric AH cell slow afterhyperpolarization (sAHP) by inhibiting a Ca-activated K (IK(Ca)) channel. We tested whether luminal LR could acutely decrease motility in an ex vivo perfusion model of naive Balb/c jejunum. Live LR dose dependently decreased motor complex pressure wave amplitudes with 9- to 16-min onset latency and an IC(50) of 5 × 10(7) cells/ml Krebs. Heat-killed LR or another live commensal, Lactobacillus salivarius, were without effect. The IK(Ca) channel blocker TRAM-34, but neither the opener (DCEBIO) nor the hyperpolarization-activated cationic channel inhibitor ZD7288 (5 μM) (or TTX 1 μM), mimicked the LR effect on motility acutely ex vivo. We provide evidence for a rapid, strain-specific, dose-dependent action of a live Lactobacillus on small intestinal motility reflexes that recapitulates the long-term effects of LR ingestion. These observations may be useful as a first step to unraveling the pathways involved in bacteria to the nervous system communication.
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease, represent the heterogeneous outcome of three colliding influences: genetic risk factors, environmental modifiers, and immune effector mechanisms of tissue injury. The nature of these inputs is complex, with each having distinct and overlapping contributions to ulcerative colitis and Crohn's disease. Identification of specific genetic risk factors has improved the understanding of specific pathways to disease, but the primacy of environmental or lifestyle factors linked to changes in the gut microbiota, particularly in early life, is increasingly evident. Clarification of the molecular basis of host-microbe interactions in health and in susceptible individuals promises novel therapeutic strategies.
Aberrant immune responses toward commensal gut bacteria can result in the onset and perpetuation of inflammatory bowel diseases (IBD). Reduced microbiota diversity in conjunction with lower proportion of Gram positive and higher proportion of Gram negative bacteria than in healthy subjects is frequently reported in IBD patients. In a subset of IBD patients, E. coli strains with specific features trigger disease. Important molecular mechanisms underlying this effect have been identified. However, in the majority of patients the exact nature of host-microbe interactions that contribute to IBD development has so far not been defined. The application of metagenomic techniques may help to identify bacterial functions that are involved in the aggravation or alleviation of IBD. Subsequently, the relevance for disease development of bacterial candidate genes may be tested taking advantage of reductionist animal models of chronic gut inflammation. This approach may help to identify bacterial functions that can be targeted in future concepts of IBD therapy.
Irritable Bowel Syndrome (IBS) is a clinically heterogeneous disorder which is likely to involve a number of causative factors. The contribution of altered intestinal microbiota composition or function to this disorder is controversial, and is the subject of much current research. Until recently, the technical limitations of the methodologies available have not permitted an adequate survey of low-abundance microbial species. Recent technological developments have enabled the analysis of the global population of the microbiome using high through-put, culture independent, 16S rRNA amplicon pyrosequencing. Using these new methodologies, we are able to gain important biological insights into the link between functional bowel disorders and the microbiome. This addendum contextualizes and summarizes the results of these studies, and defines the future challenges and opportunities in the field.
Probiotic bacteria exhibit a variety of properties, which are unique to a particular strain. Lactobacillus acidophilus-SDC 2012, 2013 are new strains isolated from Korean infants’ feces. The potential utility of Lactobacillus acidophilus-SDC 2012, 2013 in irritable bowel syndrome (IBS) was studied. Forty IBS patients were randomized into a placebo (n=20) and probiotics group (n=20). Four weeks of treatment with L. acidophilus-SDC 2012, 2013 was associated with a reduced score for abdominal pain or discomfort compared to the baseline (P=0.011). The percent reduction in abdominal pain or discomfort exceeded the placebo scores by more than 20% (23.8 and 0.2%
for probiotics and placebo, respectively, P=0.003). There was a significant difference in the proportion of responders between the probiotics and placebo groups (P=0.011). There was no drop out or adverse events for either group during the study period. Lactobacillus acidophilus-SDC 2012, 2013 appeared to have a beneficial effect in patients with IBS. Further studies are warranted.
Our understanding of the composition and function of the human gut microbiota has improved dramatically in recent years. In this review, major milestones along this path will be reviewed. The methodological developments that underpinned this acceleration of scientific progress are discussed. We review the infant microbiota with special reference to colonization, succession and stabilization events. The healthy adult microbiota is then described, including reference to selected conditions that perturb the microbiota such as antibiotic treatment, bowel dysfunction and obesity. We put special emphasis on the special issues that characterize elderly subjects, including the challenges provided by “inflamm-aging”, with reference to how the microbiota might interact with these processes. Lastly, the elderly intestinal metagenomics project ELDERMET is described, which aims to establish the composition and function of the gut microbiota in several hundred Irish subjects.
Management of recurrent Clostridium difficile-associated disease (CDAD), particularly in elderly patients, remains clinically challenging. Faecal transplantation (FT) may restore normal microbiota and break the cycle of recurrent CDAD.
To critically appraise the clinical research evidence on the safety and effectiveness of FT compared with standard care in the treatment of patients with CDAD.
A comprehensive literature search was conducted by a research librarian to identify relevant studies published between 2000 and 2011. The Cochrane Library, PubMed, EMBASE, CINAHL, Biological Abstracts, BIOSIS Previews and Web of Science were searched using the following Medical Subject Headings (MeSH) terms and keywords, alone or in combination: Clostridium infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon flora/gastrointestinal/nasogastric tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion. Methodological quality of the included case series studies was assessed in terms of patient selection criteria, consecutive recruitment, prospective data collection, reporting of lost to follow-up, and follow-up rates.
No controlled studies were found. Based on the weak evidence from seven full-text case series studies of 124 patients with recurrent/refractory CDAD, FT appears to be a safe and effective procedure. In most cases (83%) symptoms improved immediately after the first FT procedure, and some patients stayed diarrhoea free for several months or years.
Although these results appear to be promising, the treatment effects of faecal transplantation cannot be determined definitively in the absence of a control group. Results from randomised controlled trials that compare faecal transplantation to oral vancomycin without or with a taper regimen will help to better define the role of faecal transplantation in the management of recurrent CDAD.
The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. The constituents of the microbiota--bacteria, viruses, and eukaryotes--have been shown to interact with one another and with the host immune system in ways that influence the development of disease. We review these interactions and suggest that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in our microbiota.