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Gut microbiota: Changes throughout the lifespan from infancy to elderly

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Abstract

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.

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... From lifespan experiments in animals [109,110] to the analysis of the microbiome over the human lifespan (for an overview, see [111,112]) and of centenarians [113,114], a plethora of evidence shows that the microbiome is not only associated with diseases, e.g., gastrointestinal diseases such as IBS (for an overview, see [115]) and IBD (for an overview, see [116]), diabetes, metabolic liver disease [117], and allergies (for an overview, see [118]), but also aging (for an overview, see [119]) and inflammaging (for an overview, see [8]). ...
... When evaluating the microbiome, two factors are commonly considered that have a substantial impact on health and disease: stability and diversity, with a more stable and diverse microbiome generally being associated with better health (for an overview, see [120]). Starting with birth [121], the individual microbiome is subject to change throughout life [111,122]. The greatest alterations occur during our infancy when the personal microbiome is in its developing stage. ...
... This stage is followed by the adult microbiome, which has the highest stability. With further aging, the microbiome becomes again less stable (Figure 3) [123] (and for an overview, see [111,124,125]). . Stability of microbiota composition over the lifetime. ...
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Article
The intestinal barrier, composed of the luminal microbiota, the mucus layer, and the physical barrier consisting of epithelial cells and immune cells, the latter residing underneath and within the epithelial cells, plays a special role in health and disease. While there is growing knowledge on the changes to the different layers associated with disease development, the barrier function also plays an important role during aging. Besides changes in the composition and function of cellular junctions, the entire gastrointestinal physiology contributes to essential age-related changes. This is also reflected by substantial differences in the microbial composition throughout the life span. Even though it remains difficult to define physiological age-related changes and to distinguish them from early signs of pathologies, studies in centenarians provide insights into the intestinal barrier features associated with longevity. The knowledge reviewed in this narrative review article might contribute to the definition of strategies to prevent the development of diseases in the elderly. Thus, targeted interventions to improve overall barrier function will be important disease prevention strategies for healthy aging in the future.
... Changes in the butyrate-producing bacteria belonging to, for example, the families Lachnospiraceae and Ruminococcaceae are of special importance in overall gut health and in the development of numerous inflammatory conditions [37][38][39]. The elderly gut microbiota profile differs from the healthy adult one, and studies have reported a decrease in the overall diversity and species diversity for Bacteroides, Prevotella, Bifidobacterium, and Lactobacillus along with an increase in the species number within the Enterobacteriaceae, Clostridium, Proteobacteria, staphylococci, and streptococci [40][41][42][43]. ...
... This is even more true in the case of the elderly, whose gut micro-biota display greater inter-individual variability than that of younger adults [92]. This variability is caused by many factors, such as changes in digestion, bowel function, medication, everyday living environment, mobility, and, perhaps most importantly, diet [41][42][43]92]. Patterns in the microbiota composition also differ between geographical regions, which highlights the danger of generalizing health-related observations in the elderly gut microbiota [42,43,93]. ...
... This variability is caused by many factors, such as changes in digestion, bowel function, medication, everyday living environment, mobility, and, perhaps most importantly, diet [41][42][43]92]. Patterns in the microbiota composition also differ between geographical regions, which highlights the danger of generalizing health-related observations in the elderly gut microbiota [42,43,93]. Because defining a healthy elderly gut microbiota is challenging, it cannot be concluded that the lower gut microbiota diversity of rural-second-home users is a sign of gut dysbiosis, especially since the community composition did not differ between the studied groups. ...
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Article
According to the hygiene and biodiversity hypotheses, increased hygiene levels and reduced contact with biodiversity can partially explain the high prevalence of immune-mediated diseases in developed countries. A disturbed commensal microbiota, especially in the gut, has been linked to multiple immune-mediated diseases. Previous studies imply that gut microbiota composition is associated with the everyday living environment and can be modified by increasing direct physical exposure to biodiverse materials. In this pilot study, the effects of rural-second-home tourism were investigated on the gut microbiota for the first time. Rural-second-home tourism, a popular form of outdoor recreation in Northern Europe, North America, and Russia, has the potential to alter the human microbiota by increasing exposure to nature and environmental microbes. The hypotheses were that the use of rural second homes is associated with differences in the gut microbiota and that the microbiota related to health benefits are more diverse or common among the rural-second-home users. Based on 16S rRNA Illumina MiSeq sequencing of stool samples from 10 urban elderly having access and 15 lacking access to a rural second home, the first hypothesis was supported: the use of rural second homes was found to be associated with lower gut microbiota diversity and RIG-I-like receptor signaling pathway levels. The second hypothesis was not supported: health-related microbiota were not more diverse or common among the second-home users. The current study encourages further research on the possible health outcomes or causes of the observed microbiological differences. Activities and diet during second-home visits, standard of equipment, surrounding environment, and length of the visits are all postulated to play a role in determining the effects of rural-second-home tourism on the gut microbiota.
... In general, lower levels of Firmicutes (mainly Clostridium cluster XIVa and Faecalibacterium prausnitzii) and Actinobacteria (mainly bifidobacteria), together with increased populations of Proteobacteria, have been found when comparing with adults (Salazar et al., 2017). Elderly people may also have reduced dentition and chewing strength, together with a loss of appetite, which can lead to a limited variety of food ingredients that support the limited microbial diversity (O'Toole and Claesson, 2010). These changes are responsible for a decrease in short chain fatty acids (SCFA) production and shift from a predominantly saccharolytic metabolism (normally observed in adults) toward a predominantly putrefactive metabolism (Woodmansey et al., 2004). ...
... In this context, considering that the inflammatory status of this group is highly modulated by the gut microbiota (Guigoz et al., 2008) and that external factors such as diet and lifestyle are crucial for this modulation (O'Toole and Claesson, 2010), functional food turns to be an attractive target to study. ...
... Another characteristic widely observed for this part of the population is a decline in the levels and diversity of bifidobacteria (Woodmansey et al., 2004;Arboleya et al., 2016), possibly leading to a reduced immune responsiveness and an increased susceptibility to gastrointestinal infections (Woodmansey, 2007). In some cases, reduced levels of Clostridium cluster XIVa and Faecalibacterium were described (O'Toole and Claesson, 2010;Salazar et al., 2013Salazar et al., , 2019. ...
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Article
Elderly people are an important part of the global population who suffer from the natural processes of senescence, which lead to changes in the gut microbiota composition. These modifications have a great impact on their quality of life, bringing a general putrefactive and inflammatory status as a consequence. Some of the most frequent conditions related to this status are constipation, undernutrition, neurodegenerative diseases, susceptibility to opportunistic pathogens, and metabolic disbalance, among others. For these reasons, there is an increasing interest in improving their quality of life by non-invasive treatments such as the consumption of probiotics, prebiotics, and synbiotics. The aim of the present mini-review is to describe the benefits of these functional supplements/food according to the most recent clinical and pre-clinical studies published during the last decade. In addition, insights into several aspects we consider relevant to improve the quality of future studies are provided.
... It is accompanied by a reduction in gastrointestinal functions including intestinal motility, digestive and absorptive functions, as well as immune responses [3][4][5][6][7][8][9], in addition to changes in diet and lifestyle in the elderly [10,11]. Moreover, many recent studies have shown that compositional and functional abnormalities of the human gut microbiota (dysbiosis) are correlated with in ammatory disorders and metabolic syndrome, including in ammatory bowel disease [6], irritable bowel syndrome [12], type 2 diabetes (T2D) [13,14] and obesity [15][16][17]. ...
... Indeed, fecal microbiota transplantation from middle-age SPF mice into young GF mice resulted in enhanced weight gain and impaired glucose tolerance compared to mice colonized with microbiota from young SPF mice, suggesting that the middle-age gut microbiota has the potential to induce an obese-type phenotype. The ability of the host to degrade and absorb proteins, lipids and polysaccharides declines with age [3][4][5]. This results in non-digested nutrients owing into the lower intestine [3,4]. ...
... The ability of the host to degrade and absorb proteins, lipids and polysaccharides declines with age [3][4][5]. This results in non-digested nutrients owing into the lower intestine [3,4]. In fact, the concentration of soluble starch in feces was signi cantly increased in middleage GF mice compared to young GF mice, as were food-derived sugars such as sucrose, maltose and maltotriose in middle-age SPF mice (Fig. 2h). ...
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Preprint
Background: Aging is a progressive decline of cellular functions that ultimately affects whole-body homeostasis. Alterations in the gut microbiota associated with aging have been reported, however the molecular basis of the relationships between host aging and the gut microbiota is poorly understood. Result: By using longitudinal microbiome and metabolome characterization, we show that the aging-related alterations in the intestinal environment lead to gut dysbiosis with a potential to induce obesity in mice. In middle-age mice, we observed more than a 2-fold increase in fecal carbohydrates derived from dietary polysaccharides and a significant reduction of gut microbial diversity resembling the microbiota characteristic of obese mice. Consistently, fecal microbiota transplantation from middle-age specific pathogen-free (SPF) mice into young germ-free (GF) mice resulted in increased weight gain and impaired glucose tolerance. Conclusion: Our findings provide new insights into the relationships between host aging and gut dysbiosis and may contribute to the development of a possible solution to aging-related obesity.
... Внутриутробный и неонатальный периоды жизни -критические этапы формирования микробиома плода, от которых во многом зависит состояние здоровья человека в течение всей жизни [6,10]. Начиная с возраста 2-3 лет МК детей практически полностью повторяет по составу МК взрослых, а окончательно формируется к концу пубертатного периода [11]. Первоначальное становление и формирование неонатального микробиома является мультифакторным процессом и во многом зависит от способа родоразрешения, типа вскармливания ребенка, лекарственной терапии, условий окружающей среды [12]. ...
... МК детей, рожденных естественным путем, преимущественно представлена вагинальной флорой матери (Prevotella, Sneathia и Lactobacillus) [13]. Во время естественных родов факультативные анаэробы колонизируют кишечник младенца, создавая анаэробную среду в течение первых нескольких дней жизни для роста облигатных анаэробов (таких как Bacteroides и Bifidobacterium) [11,14,15]. У детей, рожденных путем кесарева сечения, МК характеризуется скудным видовым разнообразием, низким содержанием Bifidobacterium и Bacteroides, а также наличием бактерий, присутствующих на кожных покровах матери (Staphylococcus, Acinetobacter, Corynebacterium и Propionibacterium) [16]. ...
Article
At the beginning of the XXI century, with the advent of technical capabilities and new methods of genes sequencing, the attention of researchers to the study of the human metagenome has significantly increased. The interaction between changes in the qualitative and quantitative composition of the gut microbiota (GM) and various diseases is being actively studied, a search for specific metabolites and genes of microorganisms that may be associated with the development, in particular, of immune-mediated diseases is underway. In recent years, a lot of new data have been published on the possible contribution of gut flora dysbiosis to the development of Type 1 Diabetes Mellitus (T1DM), while the first assumptions were put forward as far back as 1970s. The search for pathogenetic mechanisms of GM influence on the development and progression of T1DM is becoming an increasingly relevant objective, since in recent years the incidence of T1DM is rapidly increasing, which is a serious health problem throughout the world. This review discusses the current ideas about the role of GM in the immunopathogenesis of T1DM, new data on the near-term prospects in the study of the human macrogenome, current ideas about the role of GM in the immunopathogenesis of T1DM, and the possibility of applying this knowledge by the practitioner.
... However, various external factors may influence the in vivo colonization ability of GEBs. The key influencing factor is the location of GEBs in the body because each bacterium in our body has a corresponding colonization area in which the microenvironment formed by longperiod interactions with other bacteria and mammalian cells provides a safe place for them to proliferate with high genetic stability (O'Toole and Claesson, 2010;Zou et al., 2019;Tochitani, 2021). Therefore, the disease location in the body determines the species of chassis bacterium, thus enhancing their colonization and reducing the off-target effects of their secreted substances (Dosoky et al., 2020). ...
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Advances in synthetic biology and the clinical application of bacteriotherapy enable the use of genetically engineered bacteria (GEB) to combat various diseases. GEB act as a small ‘machine factory’ in the intestine or other tissues to continuously produce heterologous proteins or molecular compounds and, thus, diagnose or cure disease or work as an adjuvant reagent for disease treatment by regulating the immune system. Although the achievements of GEBs in the treatment or adjuvant therapy of diseases are promising, the practical implementation of this new therapeutic modality remains a grand challenge, especially at the initial stage. In this review, we introduce the development of GEBs and their advantages in disease management, summarize the latest research advances in microbial genetic techniques, and discuss their administration routes, performance indicators and the limitations of GEBs used as platforms for disease management. We also present several examples of GEB applications in the treatment of cancers and metabolic diseases and further highlight their great potential for clinical application in the near future.
... However, since CVA shows a circadian rhythm, 24-h measurements could provide more precise insights into microbiota-brain communication (Valladares et al. 2008). Moreover, HRV and microbiota patterns seem to be age-dependent and change throughout the lifespan (Umetani et al. 1998;Lehofer et al. 1999;O'Toole and Claesson 2010). Additionally, both, gut microbiota and vagal nerve function seem to be closely interconnected with inflammation (Pavlov and Tracey 2012;Soares-Miranda et al. 2012;Al Bander et al. 2020). ...
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Article
Introduction: A functional reciprocity between the gut microbiome and vagal nerve activity has been suggested, however, human studies addressing this phenomenon are limited. Methods: Twenty-four-hour cardiac vagal activity (CVA) was assessed from 73 female participants (aged 24.5 ± 4.3 years). Additionally, stool samples were subjected to 16SrRNA gene analysis (V1-V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyse microbiome data. Additionally, inflammatory parameters (such as CRP and IL-6) were derived from serum samples. Results: Daytime CVA correlated significantly with gut microbiota diversity (r sp = 0.254, p = 0.030), CRP (r sp = -0.348, p = 0.003), and IL-6 (r sp = -0.320, p = 0.006). When the group was divided at the median of 24 h CVA (Mdn = 1.322), the following features were more abundant in the high CVA group: Clostridia (Linear discriminant analysis effect size (LDA) = 4.195, p = 0.029), Clostridiales (LDA = 4.195, p = 0.029), Lachnospira (LDA = 3.489, p = 0.004), Ruminococcaceae (LDA = 4.073, p = 0.010), Faecalibacterium (LDA = 3.982, p = 0.042), Lactobacillales (LDA = 3.317, p = 0.029), Bacilli (LDA = 3.294, p = 0.0350), Streptococcaceae (LDA = 3.353, p = 0.006), Streptococcus (LDA = 3.332, p = 0.011). Based on Dirichlet multinomial mixtures two enterotypes could be detected, which differed significantly in CVA, age, BMI, CRP, IL-6, and diversity. Conclusions: As an indicator of gut-brain communication, gut microbiome analysis could be extended by measurements of CVA to enhance our understanding of signalling via microbiota-gut-brain-axis and its alterations through psychobiotics.
... Human gut microbiota is unique, stable, and change-resistant [13] . Despite this, their composition changes over time [14] . Birth method [15,16] , host age, lifestyle, medications, and diet all affect the gut microbiota [17][18][19][20] . ...
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Article
Malabsorption is a very important topic that impacts the health of people all over the world. The main objective of the present study is to review the literature regarding malabsorption and the role of microbes in malabsorption. Malabsorption can be attributed by several factors such as bacteria, vitamins, and disturbance of intestinal mucosa. The present study focused on microbial reasons due to their species diversity including bacteria and parasites. It seems that microbial origin has become hidden with time and not well considered in clinical practice. In some parts of the world, parasites are still existing and their role in malabsorption can not be ignored.
... It is well-known that the pro-inflammatory response shows a progressive increase with an increase in age [48,49]. During inflammatory aging, the balance of the gut microbiota is gradually lost, and the composition and diversity of the gut microbiota are altered, causing chronic systemic low-level inflammation [50][51][52] and resulting in the deterioration of intestinal tissue function and an intensified inflammatory response of the body [53]. After dietary intervention, APF, APS, and APRS significantly downregulated the relative mRNA expression of the p53 aging gene in aging mice and significantly upregulated expression of anti-aging gene SIRT1, suggesting that RS dietary intervention had potential anti-aging effects and APRS had the best effect, followed by APS and APF. ...
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Article
This study aimed to compare the regulatory effects of Arenga pinnata retrograded starch (APRS), Arenga pinnata starch (APS), and whole Arenga pinnata flour (APF) on gut microbiota and improvement of intestinal inflammation in aged mice. APF, APS, and APRS altered gut microbiota composition and exhibited different prebiotic effects. Bifidobacterium showed the greatest increase in feces of aged mice fed APF. The abundance of genus Lachnospiraceae_NK4A136 was highest in the APS group. APRS supplementation led to a greatest increasement in abundance of Lactobacillus, Roseburia, and Faecalibacterium prausnitzii. APRS induced significantly more short-chain fatty acid (SCFAs) production than APF and APS. APF, APS, and APRS treatments improved intestinal inflammation in aged mice and the order of ameliorative effect was APRS > APS > APF. APRS significantly decreased relative mRNA expression of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and increased anti-inflammatory cytokines (IL-10). In addition, APF, APS, and APRS significantly downregulated the relative mRNA expression of senescence-associated gene p53 and upregulated the expression of anti-aging gene Sirt1. These results provide potentially useful information about the beneficial effects of Arenga pinnata products on human health.
... Furthermore, gut microbiota composition is often imbalanced (i.e., dysbiosis) in older adults, especially in those who are frail and/or who have been institutionalized (13,14). Compared to healthier individuals, these populations frequently have lower microbial diversity, larger numbers of opportunistic pathogens, and lower levels of species that produce anti-inflammatory and insulinsensitizing metabolites (e.g., Faecalibacterium prausnitzii) (14,15). Recent studies have found that the gut microbiota and skeletal muscle engage in cross-talk (5,(16)(17)(18)(19)(20), which leads us to hypothesize that strategies targeting gut community composition and function could help frail elderly individuals improve their skeletal muscle health. ...
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Article
The aim of this study was to identify a probiotic-based strategy for maintaining muscle anabolism in the elderly. In previous research, we found that individuals experiencing short bowel syndrome (SBS) after an intestinal resection displayed beneficial metabolic adjustments that were mediated by their gut microbes. Thus, these bacteria could potentially be used to elicit similar positive effects in elderly people, who often have low food intake and thus develop sarcopenia. Gut bacterial strains from an SBS patient were evaluated for their ability to (1) maintain Caenorhabditis elegans survival and muscle structure and (2) promote protein anabolism in a model of frail rodents (18-month-old rats on a food-restricted diet: 75% of ad libitum consumption). We screened a first set of bacteria in C. elegans and selected two Lacticaseibacillus casei strains (62 and 63) for further testing in the rat model. We had four experimental groups: control rats on an ad libitum diet (AL); non-supplemented rats on the food-restricted diet (R); and two sets of food-restricted rats that received a daily supplement of one of the strains (∼10 ⁹ CFU; R+62 and R+63). We measured lean mass, protein metabolism, insulin resistance, cecal short-chain fatty acids (SCFAs), and SCFA receptor expression in the gut. Food restriction led to decreased muscle mass [−10% vs. AL ( p < 0.05)]. Supplementation with strain 63 tempered this effect [−2% vs. AL ( p > 0.1)]. The mechanism appeared to be the stimulation of the insulin-sensitive p-S6/S6 and p-eIF2α/eIF2α ratios, which were similar in the R+63 and AL groups ( p > 0.1) but lower in the R group ( p < 0.05). We hypothesize that greater SCFA receptor sensitivity in the R+63 group promoted gut-muscle cross talk [GPR41: +40% and GPR43: +47% vs. R ( p < 0.05)]. Hence, strain 63 could be used in association with other nutritional strategies and exercise regimes to limit sarcopenia in frail elderly people.
... The experimental study of gut microbiota requires culturing methods that are adapted to their specific requirements. The gut microbiota is mainly comprised of strict and facultative anaerobic members with complex nutritional demands, making these micro-organisms difficult to cultivate with common microbiological techniques (O'Tool & Claesson, 2010;Vacca, 2017). Initially, an anaerobic environment is required, which is generally created by oxygen replacement with anoxic gases, such as nitrogen (N 2 ), hydrogen (H 2 ) and carbon dioxide (CO 2 ). ...
Article
Aims: This research aimed to develop and validate a cultivation and monitoring protocol that is suitable for a surrogate microbial community that accounts for the gut microbiota of the ileum of the small intestine. Methods and results: Five bacterial species have been selected as representatives of the ileal gut microbiota and a general anaerobic medium (MS-BHI, as minimally supplemented BHI) has been constructed and validated against BCCM/LGM recommended and commercial media. Moreover, appropriate selective/differential media have been investigated for monitoring each ileal gut microbiota surrogate. Results showed that MS-BHI was highly efficient in displaying individual and collective behavior of the ileal gut microbiota species, when compared with other types of media. Likewise, the selective/differential media managed to identify and describe the behavior of their targeted species. Conclusions: MS-BHI renders a highly efficient, inexpensive and easy-to-prepare cultivation and enumeration alternative for the surrogate ileal microbiota species. Additionally, the selective/differential media can identify and quantify the bacteria of the surrogate ileal microbial community. Significance and impact of study: The selected gut microbiota species can represent an in vitro ileal community, forming the basis for future studies on small intestinal microbiota. MS-BHI and the proposed monitoring protocol can be used as a standard for gut microbiota studies that utilize conventional microbiological techniques.
... Ageing and age-related diseases are frequently associated to a modification of the overall number and species diversity of the complex ecosystem of bacteria, fungal, and viral species living as symbiotic companions in our body from birth to death. 16 Moreover, there is increasing awareness of the association between gut microbiota and brain functions, which has come to be known as the gut-brain axis, 17,18 affecting cognitive outcomes and decline. 19 All these physiological changes, which are associated with possible concomitant presence of chronic diseases (e.g. ...
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Article
Ageing is an unavoidable progressive process causing many changes of the individual life. However, if faced in an efficient way, living longer in a healthy status could be an opportunity for all. In this context, food consumption and dietary patterns are pivotal factors in promoting active and healthy ageing. The development of food products tailored for the specific needs of the elderly might favour the fulfilment of nutritionally balanced diets, while reducing the consequences of malnutrition. To this aim, the application of a food structure design approach could be particularly profitable, being food structure responsible to the final functionalities of food products. In this narrative review, the physiological changes associated to food consumption occurring during ageing were firstly discussed. Then, the focus shifted to the possible role of food structure in delivering target functionalities, considering food acceptability, digestion of the nutrients, bioactive molecules and probiotic bacteria.
... The human gut microbiota is unique and relatively stable, and thus highly resilient to change [14]. In spite of this, they are also dynamic, and their composition is remodelled during different stages of our lifespan [15]. Several factors, such as the birth method of a child [16,17]; the age of the host [18]; lifestyle; medications; and, most importantly, diet [19][20][21], significantly modulate the composition of the gut microbiota. ...
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Article
B vitamins act as coenzymes in a myriad of cellular reactions. These include energy production, methyl donor generation, neurotransmitter synthesis, and immune functions. Due to the ubiquitous roles of these vitamins, their deficiencies significantly affect the host's metabolism. Recently, novel roles of B vitamins in the homeostasis of gut microbial ecology and intestinal health continue to be unravelled. This review focuses on the functional roles and biosynthesis of B vitamins and how these vitamins influence the growth and proliferation of the gut microbiota. We have identified the gut bacteria that can produce vitamins, and their biosynthetic mechanisms are presented. The effects of B vitamin deficiencies on intestinal morphology, inflammation, and its effects on intestinal disorders are also discussed.
... Intestinal microbiota plays a vital role in maintaining intestinal homeostasis of humans and animals (Ma et al., 2017;Shi et al., 2017). However, the gastrointestinal tract of the fetus is sterile; therefore, early colonization of the infant gastrointestinal tract is crucial for the overall health of the infant (Wall et al., 2009;O'Toole and Claesson, 2010). Besides, intestinal microbiota is dynamic and easily affected by various factors (physiological and environmental); dietary strategies are effective approaches to modulate the composition of the intestinal microbiota for maintaining host health (Wan et al., 2020). ...
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Article
Manno-oligosaccharide (MOS) is a prebiotic derived from natural plants or yeasts. Here, we explored the response of intestinal microbiota and epithelial functions after ingestion of MOS in a porcine model. Sixteen pigs were randomly assigned into two treatments and fed with basal or MOS-containing (0.3% MOS) diet for 21 days. Results showed that MOS supplementation increased the cecal acetate content and ileal 16S rRNA gene copies ( p < 0.05). Importantly, MOS decreased the abundance of phylum Proteobacteria in cecal digesta ( p < 0.05). Moreover, MOS elevated the expression level of SCL5A8 and GPR109A but decreased the expression levels of HDAC1 and TNF-α in the ileal and cecal mucosa ( p < 0.05). MOS upregulated the expression levels of tight-junction protein (ZO-1, claudin-1, and occludin) and IGF-1 in the ileum and cecum ( p < 0.05). This study presents the alteration of intestinal microbiota composition and intestinal barrier function after MOS administration, and facilitates our understanding of the mechanisms behind the dietary MOS-modulated intestinal microbiota and health.
... Gut microbiota is abundant in complexity and diversity, and several different microorganisms such as archaea, bacteria, fungi, and viruses reside in the human gastrointestinal tract [9]. The microbiota is maternally acquired at birth [10] and changes throughout the lifespan dominated by dietary habits and environmental signals [11]. Gut microbial heterogeneity amongst communities has also been observed with implications in health and disease [12,13]. ...
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Article
The significance of diversity, composition, and functional attributes of the gut microbiota in shaping human health is well recognized. Studies have shown that gut microbiota is closely linked to human aging, and changes in the gut microbiome can predict human survival and longevity. In addition, a causal relationship between gut microbiota dysbiosis and chronic age-related disorders is also becoming apparent. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between the gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the evolving relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis and diseases, have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship between the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity-promoting therapies. Graphical abstract
... Although R. gnavus was found to increase in pathological conditions, such as inflammatory bowel disease [46], it can be predominant in the infant's gut as bifidobacteria, independently by the type of feeding or delivering. As a matter of fact, ruminococci belonging to Lachnospiraceae family have the same pathway of bifidobacteria for complex sugar and mucin degradation and they release metabolites that could be important for the evolution of a more mature microbiota [32,47]. At a functional level, it has been suggested that R. gnavus might promote protein synthesis and lean body mass formation, preventing amino acid oxidation; furthermore, data obtained from murine models indicated this organism could improve malnutrition and metabolic abnormalities [48]. ...
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Article
Propionic Acidemia (PA) is a rare inherited metabolic disorder caused by the enzymatic block of propionyl-CoA carboxylase with the consequent accumulation of propionic acid, which is toxic for the brain and cardiac cells. Since a considerable amount of propionate is produced by intestinal bacteria, interest arose in the attempt to reduce propionate-producing bacteria through a monthly antibiotic treatment of metronidazole. In the present study, we investigated the gut microbiota structure of an infant diagnosed at 4 days of life through Expanded Newborn Screening (NBS) and treated the child following international guidelines with a special low-protein diet, specific medications and strict biochemical monitoring. Microbiota composition was assessed during the first month of life, and the presence of Bacteroides fragilis, known to be associated with propionate production, was effectively decreased by metronidazole treatment. After five antibiotic therapy cycles, at 4 months of age, the infant was supplemented with a daily mixture of three bifidobacterial strains, known not to be propionate producers. The supplementation increased the population of bifidobacteria, with Bifidobacterium breve as the dominating species; Ruminococcus gnavus, an acetate and formate producer, was also identified. Metabarcoding analysis, compared with low coverage whole metagenome sequencing, proved to capture all the microbial biodiversity and could be the elected tool for fast and cost-effective monitoring protocols to be implemented in the follow up of rare metabolic disorders such as PA. Data obtained could be a possible starting point to set up tailored microbiota modification treatment studies in the attempt to improve the quality of life of people affected by propionic acidemia.
... The OTUs from the above analysis were reconfirmed by the RDP classifier to determine the critical microbial markers at the genus/species levels. Age is one of the crucial factors that need to be considered with regard to gut microbiota profiles, and gut microbiota patterns will change with age (i.e., from infants to elderly patients) 9,26 . Age differs between premenopausal and postmenopausal women, which is accompanied by different patterns of gut microbiota 24,25 . ...
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In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.
... Accumulating evidence indicates that the host microbiota regulates the maternal and fetal immune interaction as well as the birth outcome [19][20][21]. In addition, current lines of evidence also indicate that the host microbiota-generated metabolites control various metabolic mechanisms and inflammatory processes including PTB ( Figure 1) [22,23]. ...
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Article
Preterm birth (PTB) refers to the birth of infants before 37 weeks of gestation and is a challenging issue worldwide. Evidence reveals that PTB is a multifactorial dysregulation mediated by a complex molecular mechanism. Thus, a better understanding of the complex molecular mechanisms underlying PTB is a prerequisite to explore effective therapeutic approaches. During early pregnancy, various physiological and metabolic changes occur as a result of endocrine and immune metabolism. The microbiota controls the physiological and metabolic mechanism of the host homeostasis, and dysbiosis of maternal microbial homeostasis dysregulates the mechanistic of fetal developmental processes and directly affects the birth outcome. Accumulating evidence indicates that metabolic dysregulation in the maternal or fetal membranes stimulates the inflammatory cytokines, which may positively progress the PTB. Although labour is regarded as an inflammatory process, it is still unclear how microbial dysbiosis could regulate the molecular mechanism of PTB. In this review based on recent research, we focused on both the pathological and therapeutic contribution of microbiota-generated metabolites to PTB and the possible molecular mechanisms.
... Several studies have demonstrated that aging is associated with a shift in microbial composition and decreased diversity [25,26]. Characterization of the fecal microbiota composition of 161 elderly from the ELDERMET project revealed that the microbiota composition of elderly is rather distinct compared to younger adults [13]. ...
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Article
Increasing evidence suggests that probiotic supplementation may be efficacious in counteracting age-related shifts in gut microbiota composition and diversity, thereby impacting health outcomes and promoting healthy aging. However, randomized controlled trials (RCTs) with probiotics in healthy older adults have utilized a wide variety of strains and focused on several different outcomes with conflicting results. Therefore, a systematic review was conducted to determine which outcomes have been investigated in randomized controlled trials with probiotic supplementation in healthy older adults and what has been the effect of these interventions. For inclusion, studies reporting on randomized controlled trials with probiotic and synbiotic supplements in healthy older adults (defined as minimum age of 60 years) were considered. Studies reporting clinical trials in specific patient groups or unhealthy participants were excluded. In addition to assessment of eligibility and data extraction, each study was examined for risk of bias and quality assessment was performed by two independent reviewers. Due to the heterogeneity of outcomes, strains, study design, duration, and methodology, we did not perform any meta-analyses and instead provided a narrative overview of the outcomes examined. Of 1997 potentially eligible publications, 17 studies were included in this review. The risk of bias was low, although several studies failed to adequately describe random sequence generation, allocation concealment, and blinding. The overall study quality was high; however, many studies did not include sample calculations, and the majority of studies had a small sample size. The main outcomes examined in the trials included microbiota composition, immune-related measurements, digestive health, general well-being, cognitive function, and lipid and other biomarkers. The most commonly assessed outcome with the most consistent effect was microbiota composition; all but one study with this outcome showed significant effects on gut microbiota composition in healthy older adults. Overall, probiotic supplementation had modest effects on markers of humoral immunity, immune cell population levels and activity, as well as the incidence and duration of the common cold and other infections with some conflicting results. Digestive health, general-well-being, cognitive function, and lipid and other biomarkers were investigated in a very small number of studies; therefore, the impact on these outcomes remains inconclusive. Probiotics appear to be efficacious in modifying gut microbiota composition in healthy older adults and have moderate effects on immune function. However, the effect of probiotic supplementation on other health outcomes remains inconclusive, highlighting the need for more well-designed, sufficiently-powered studies to investigate if and the mechanisms by which probiotics impact healthy aging.
... Gut microbiota is abundant in complexity and diversity, and a number of different microorganisms such as archaea, bacteria, fungi, and viruses reside in human gastrointestinal tract (Ferreiro et al., 2018). The microbiota is maternally acquired at birth (Dominguez-Bello et al., 2010) and undergoes changes throughout the lifespan dominated by dietary habits and environmental signals (O'Toole and Claesson, 2010). Gut microbial heterogeneity amongst communities has also been observed with implications in health and disease (Das et al., 2018;Priya and Blekhman, 2019). ...
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The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.
... It is hypothesized that approximately 3.3 million microbial genes are encoded in the entire genetic repertoire of the gut microbiota [1]. In humans, one of the major influences on the microbial signatures of individuals is diet [2,3], while antibiotic use [4], exercise [5] and age [6] also have significant effects. Furthermore, the gut microbiota profiles of humans are altered in metabolic disease states such as obesity [7], type II diabetes mellitus (T2DM) [8] and cardiovascular disease (CVD) [9]. ...
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Article
Dietary fibre has long been established as a nutritionally important, health-promoting food ingredient. Modern dietary practices have seen a significant reduction in fibre consumption compared with ancestral habits. This is related to the emergence of low-fibre “Western diets” associated with industrialised nations, and is linked to an increased prevalence of gut diseases such as inflammatory bowel disease, obesity, type II diabetes mellitus and metabolic syndrome. The characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as high plasma cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Gut microbial signatures are also altered significantly in these cohorts, suggesting a causative link between diet, microbes and disease. Dietary fibre consumption has been hypothesised to reverse these changes through microbial fermentation and the subsequent production of short-chain fatty acids (SCFA), which improves glucose and lipid parameters in individuals who harbour diseases associated with dysfunctional metabolism. This review article examines how different types of dietary fibre can differentially alter glucose and lipid metabolism through changes in gut microbiota composition and function.
... As to the limitations; first, it should be noted that significant heterogeneity was present between included studies which might be due to the use of distinct protocols regarding probiotic dose and strains, study duration, and sample size. The effects of probiotics intake could also be confounded by diet [59], age [60] body mass index (BMI) [61], drugs [62], and stress [63]. As a result of these factors, the gut microbiome could be variable in terms of functioning and constituents. ...
Article
The possible effect of probiotic interventions on immunological markers in athletes is inconclusive. Therefore, to synthesize and quantitatively analyze the existing evidence on this topic, systematic literature searches of online databases PubMed, Scopus, Cochrane Library, and ISI Web of Sciences was carried out up to February 2021 to find all randomized controlled trials (RCTs) concerning the immunological effects of probiotics in athletes. In the random-effects model, weighted mean difference (WMD) and 95% confidence interval (CI) explained the net effect. The authors assessed the likelihood of publication bias via Egger's and Begg's statistics. A total of 13 RCTs (836 participants) were retrieved. Probiotic consumption reduced lymphocyte T cytotoxic count significantly (WMD=-0.08 cells×109/L; 95% CI: -0.15 to -0.01; p=0.022) with evidence of moderate heterogeneity (I2=59.1%, p=0.044) and monocyte count when intervention duration was ≤ 4 weeks (WMD=-0.08 cells×109/L; 95% CI: -0.16 to -0.001; I2=0.0%). Furthermore, leukocyte count was significantly elevated (WMD=0.48 cells×109/L; 95% CI: 0.02 to 0.93; I2=0.0%) when multi-strain probiotics were used. Probiotic supplements may improve immunological markers, including lymphocyte T cytotoxic, monocyte, and leukocyte in athletes. Further randomized controlled trials using diverse strains of probiotics and consistent outcome measures are necessary to allow for evidence-based recommendations.
... Microbial diversity in the oral cavity was stable across all age groups (Fig. 1a, Fig. S1), suggesting perhaps a limited impact of shifting from milk to solid foods on microbial species diversity in the mouth. In contrast to results of both human and mouse studies [32,37,121], we did not observe a decrease in alpha-diversity for any of the body sites in aged macaques. Interestingly, infant genitals, both penile and vaginal, had higher alpha-diversity, and young male but not female macaques had a different community structure than adults. ...
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Article
Background An individual’s microbiome changes over the course of its lifetime, especially during infancy, and again in old age. Confounding factors such as diet and healthcare make it difficult to disentangle the interactions between age, health, and microbial changes in humans. Animal models present an excellent opportunity to study age- and sex-linked variation in the microbiome, but captivity is known to influence animal microbial abundance and composition, while studies of free-ranging animals are typically limited to studies of the fecal microbiome using samples collected non-invasively. Here, we analyze a large dataset of oral, rectal, and genital swabs collected from 105 free-ranging rhesus macaques ( Macaca mulatta , aged 1 month-26 years), comprising one entire social group, from the island of Cayo Santiago, Puerto Rico. We sequenced 16S V4 rRNA amplicons for all samples. Results Infant gut microbial communities had significantly higher relative abundances of Bifidobacterium and Bacteroides and lower abundances of Ruminococcus , Fibrobacter , and Treponema compared to older age groups, consistent with a diet high in milk rather than solid foods. The genital microbiome varied widely between males and females in beta-diversity, taxonomic composition, and predicted functional profiles. Interestingly, only penile, but not vaginal, microbiomes exhibited distinct age-related changes in microbial beta-diversity, taxonomic composition, and predicted functions. Oral microbiome composition was associated with age, and was most distinctive between infants and other age classes. Conclusions Across all three body regions, with notable exceptions in the penile microbiome, while infants were distinctly different from other age groups, microbiomes of adults were relatively invariant, even in advanced age. While vaginal microbiomes were exceptionally stable, penile microbiomes were quite variable, especially at the onset of reproductive age. Relative invariance among adults, including elderly individuals, is contrary to findings in humans and mice. We discuss potential explanations for this observation, including that age-related microbiome variation seen in humans may be related to changes in diet and lifestyle.
... La variabilité inter-individus reflète principalement des facteurs environnementaux ou comportementaux, qui structurent fortement les flores microbiennes, notamment : le régime alimentaire (David et al., 2014), l'âge (O'Toole & Claesson, 2010 ;Yatsunenko et al., 2012) mais aussi la prise d'antibiotiques (Bokulich et al., 2016 ;Palleja et al., 2018), la présence d'un animal de compagnie (Kates et al., 2020), etc. ...
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Thesis
Cette thèse porte sur l'inclusion d'informations hiérarchiques dans des procédures de détection d'abondance différentielle sur des données métagénomiques. Les différents taxons qui composent le microbiote sont généralement accompagnés d'un arbre, comme la taxonomie ou la phylogénie, qui traduit une proximité biologique entre eux. Il est alors naturel de vouloir tirer parti de cette information hiérarchique afin d'augmenter la puissance des tests de détection de taxons différentiellement abondants. Dans un premier temps, nous nous sommes intéressés aux performances des procédures hiérarchiques existantes et à l'impact du choix de l'arbre sur celles-ci. Dans un second temps, nous avons développé notre propre méthode hiérarchique de détection d'abondance différentielle. Celle-ci modélise les z-scores associés à chaque taxon comme la réalisation d'un processus d'Ornstein-Uhlenbeck sur arbre avec sauts dans la valeur optimale du processus puis effectue une régression de type lasso pour déterminer les positions et intensités optimales des sauts.
... Scientific evidence has demonstrated that probiotics have the potential to relieve a variety of diseases, including inhibition of diarrhoea (Lye, Kuan, Ewe, Fung, & Liong, 2009), a reduction in lactose intolerance and irritable bowel symptoms (Pelletier, Laure-Boussuge, & Donazzolo, 2001;Moayyedi et al., 2010), and prevention of intestinal inflammatory diseases and colorectal cancer (Golowczyc, Mobili, Garrote, Abraham, & De Antoni, 2007;Rafter et al., 2007;Liong, 2008) etc. However, the diversity of the intestinal flora could be significantly reduced with an unbalanced diet and antibiotic abuse (O'Toole & Claesson, 2010), exhibiting a decrease in the number of lactic acid bacteria (LAB) and Bifidobacteria and an increase in Enterobacter and certain proteus species (Woodmansey, 2007). An imbalance in the distribution, diversity, species composition and metabolic output of gut microflora may cause a variety of intestinal diseases (Roberts et al., 2010). ...
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Article
The purpose of this study was to investigate whether soybean protein isolates (SPIs²) and soybean peptides (PEPs), as well as their hydrolysates after simulated gastrointestinal digestion (dSPIs and dPEPs), can promote the growth and short chain fatty acid (SCFA) production of Lactobacillus rhamnosus (L. rhamnosus) in vitro under mono-culture and co-culture with Escherichia coli (E. coli). We found that all the treatment groups could enhance the viable cell numbers, while the effects of PEP and dPEP occurred earlier than those of SPI and dSPI, and the production of SCFAs was improved mainly by the dPEP and dSPI groups in mono-culture. In the co-culture system, dPEP weakened the competitiveness of E. coli and improved the competitive capacity of L. rhamnosus, and the viable cell numbers of L. rhamnosus were higher than the numbers in the treated mono-culture after 8 h and 12h of cultivation.
... Developing preventive nutritional strategies to maintain or improve the quality of life of an aging population is essential and timely [45][46][47][48]. Several groups are studying diet control in the elderly, and recent reports have focused on the positive relationship between human health and the microbial flora of the human gut [49][50][51][52]. ...
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Article
Synbiotics intake can alter the composition of intestinal microbes beneficially. We aimed to detect the changes in the intestinal microbiomes of 37 healthy elderly Korean women after the intake of a synbiotic drink. This was a longitudinal study controlled with a temporal series, including a control period of 3 weeks before intake, synbiotic intake for 3 weeks, and a washout period of 3 weeks. Fecal microbiota composition was analyzed by sequencing the V3-V4 hypervariable regions of 16S rRNA. Physical fecal activity increased with improvement in fecal shape. Thirty intestinal bacterial taxa were observed to change only after the intake period. In particular, Ellagibacter appeared only after ingestion. In addition, the abundance of Terrisporobacter showed a positive correlation with C-reactive protein, triglyceride. Lachnospiraceae_uc, Eubacterium_g5, and Blautia had a positive correlation with creatinine, whereas PAC001100_g had a negative correlation with creatinine. Short-term (3 weeks) intake of symbiotic organisms changes the composition of the gut microbiota in healthy elderly Korean women.
... Bacteria that form the gut microbiota of warm-blooded animals belong to numerous phyla, but representatives of two phyla-Gram-negative Bacteroidetes and Gram-positive Firmicutescommonly form over 90% of all microbiota in healthy adults [1][2][3][4][5][6]. Bacteroidetes have a higher potential to interact with their host and degrade complex polysaccharides [7][8][9], and their metabolism commonly produces acetate, propionate and succinate [10,11]. ...
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Article
Bacteroidaceae are common gut microbiota members in all warm-blooded animals. However, if Bacteroidaceae are to be used as probiotics, the species selected for different hosts should reflect the natural distribution. In this study, we therefore evaluated host adaptation of bacterial species belonging to the family Bacteroidaceae. B. dorei, B. uniformis, B. xylanisolvens, B. ovatus, B. clarus, B. thetaiotaomicron and B. vulgatus represented human-adapted species while B. gallinaceum, B. caecigallinarum, B. mediterraneensis, B. caecicola, M. massiliensis, B. plebeius and B. coprocola were commonly detected in chicken but not human gut microbiota. There were 29 genes which were present in all human-adapted Bacteroides but absent from the genomes of all chicken isolates, and these included genes required for the pentose cycle and glutamate or histidine metabolism. These genes were expressed during an in vitro competitive assay, in which human-adapted Bacteroides species overgrew the chicken-adapted isolates. Not a single gene specific for the chicken-adapted species was found. Instead, chicken-adapted species exhibited signs of frequent horizontal gene transfer, of KUP, linA and sugE genes in particular. The differences in host adaptation should be considered when the new generation of probiotics for humans or chickens is designed.
... Previously, an Irish study based on the Eldermet Project: Dentition, Nutrition & Cognition-Community Versus Long Term Care Population (ELDERMET) cohort of 178 elderly subjects showed the relationship between diet, GM, and health status [35]. A decline in GM composition is repeatedly described in the elderly [39], with the trajectory transition from healthy to frailty observed with the significant abundances of Prevotella and Ruminococcus among healthy community dwelling elderly and Alistipes and Oscillibacter among more frail groups, respectively [35]. In addition, the GM perturbations are associated with health issues, medication usage, lifestyle factors and associated dietary changes, exercise, cohabitation patterns, and mobility [35], [40]- [42]. ...
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Thesis
The human gut is home for plethora of microbes including prokaryotic and eukaryotic organisms across all domains of the tree of life. This complex community is known as the gut microbiome (GM). Nowadays, the advances in high-throughput sequencing technology allow for studies not limited to bacteria, but also fungi, archaea, viruses and parasites in various settings across age groups, life-styles, diets, and geographical regions have been studied. Gut microbial dysbiosis have been linked to frailty in elderly, but their possible association with host health is little understood. During the course of life, imbalances in the GM is associated with significant phenotypic effects for the host such as development of metabolic disorders like obesity, elevated blood pressure, changes in serum lipids and sugar metabolism, infections, overall losses of muscle mass and functional and general physiological decline. Understanding how these disorders have been orchestrated by the interplay between prokaryotic and eukaryotic communities is of great interest with the aim of elucidating mechanistic approaches to prevent frailty and improve quality of life through healthy ageing. Generally, our work involves high throughput sequencing and conventional microbiology-based approaches for GM characterization, with special focus on prokaryote and eukaryote communities in association with dietary, metabolome, life-styles and clinical characteristics at baseline and during a 1-year intervention study investigating the effect of whey supplementation and physical training activity.
... Alteration of the co-metabolism of bile acids and vitamins has been associated with the development of metabolic diseases, such as obesity and type 2 diabetes [57]. A catalogue of the functional capacity of the human gut microbiome identified 9,879,896 genes wherein country-specific microbial signatures were found suggesting that gut microbiota composition is affected by multiple factors, such as host genetics, diet, health status, aging [58][59][60], and antibiotic administration [61]. ...
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Article
The continuous population increase of older adults with metabolic diseases may contribute to increased prevalence of sarcopenia and obesity and requires advocacy of optimal nutrition treatments to combat their deleterious outcomes. Sarcopenic obesity, characterized by age-induced skeletal-muscle atrophy and increased adiposity, may accelerate functional decline and increase the risk of disability and mortality. In this review, we explore the influence of dietary protein on the gut microbiome and its impact on sarcopenia and obesity. Given the associations between red meat proteins and altered gut microbiota, a combination of plant and animal-based proteins are deemed favorable for gut microbiota eubiosis and muscle-protein synthesis. Additionally, high-protein diets with elevated essential amino-acid concentrations, alongside increased dietary fiber intake, may promote gut microbiota eubiosis, given the metabolic effects derived from short-chain fatty-acid and branched-chain fatty-acid production. In conclusion, a greater abundance of specific gut bacteria associated with increased satiation, protein synthesis, and overall metabolic health may be driven by protein and fiber consumption. This could counteract the development of sarcopenia and obesity and, therefore, represent a novel approach for dietary recommendations based on the gut microbiota profile. However, more human trials utilizing advanced metabolomic techniques to investigate the microbiome and its relationship with macronutrient intake, especially protein, are warranted.
... Growing studies have documented microbiota of newborn meconium which influenced immune and metabolic development in early-life and might, therefore, have short and long-term health consequences (Marie-Claire et al., 2014;Tamburini et al., 2016;Milani et al., 2017). Aberrant bacterial communities can lead to disease through an altered development of the immune system (O'Toole and Claesson, 2010;Wilczynska et al., 2019). Based on results from large-scale human population and mouse studies under controlled conditions, genetics is an indispensable shaper of microbial diversity and composition related to diet, innate immunity, and energy metabolism etc. (Dicksved et al., 2008;Smith et al., 2013;Li et al., 2014). ...
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Article
The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05). The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.
... Furthermore, it plays an important role in digestion (Boulang e et al. 2016;Karst 2016), vitamin synthesis (Rowland et al. 2017;Wang et al. 2017a), safeguards against pathogens (Dupaul-Chicoine et al. 2013;Jones and Neish 2016;Gaufin et al. 2017;Hillman et al. 2017), increases fat storage efficiency, central nervous system (CNS) modulation, immune system development and maturation (Ekmekciu et al. 2017;Proctor 2019), differentiation and proliferation of intestinal epithelium (O'Hara and Shanahan 2006) and intestinal angiogenesis (Baumgart and Carding 2007) with an influence on human behaviour, thereby making it a 'vital-organ' (Amon and Sanderson 2017). Now, it is well known that the GI tract of a foetus is sterile until birth and its colonization by microbes begins at birth (Rodr ıguez et al. 2015), which is found to change throughout the life, that is, from infancy to old age (O'Toole and Claesson 2010). After vaginal delivery, the GI tract of an infant is rapidly colonized by the mother's microbes and the environment. ...
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Article
Human gut microbiota (GM) includes a complex and dynamic population of microorganisms that are crucial for well‐being and survival of the organism. It has been reported as diverse and relatively stable with shared core microbiota, including Bacteroidetes and Firmicutes as the major dominants. They are the key regulators of body homeostasis, involving both intestinal and extra‐intestinal effects by influencing many physiological functions such as metabolism, maintenance of barrier homeostasis, inflammation, and hematopoiesis. Any alteration in GM community structures not only trigger gut disorders, but also influence other organs and cause associated diseases. In recent past, the GM has been defined as a “vital organ” with its involvement with other organs; thus, establishing a link or a bi‐ or multi‐directional communication axis between the organs via neural, endocrine, immune, humoral, and metabolic pathways. Alterations in GM have been linked to several diseases known to humans; although the exact interaction mechanism between the gut and the organs is yet to be defined. In this review, the bi‐directional relationship between the gut and the vital human organs was envisaged and discussed under several headings. Furthermore, several disease symptoms were also re‐visited to re‐define the communication network between the gut microbes and the associated organs.
Article
Dietary fiber intake by humans is nowadays substantially decreasing as compared to the communities of ancestral populations. Accompanying that, the incidences of inflammatory bowel disease (IBD), allergy, and other autoimmune diseases are steadily increasing over the past 60 years, especially in high-income countries, which is partly attributed to the changing dietary habit in modern societies. Chronic inflammation triggered by Immune disorders is the central part of the pathophysiology of various non-communicable diseases. Dietary fiber intake is inexorably linked to the gut microbiome leading to the reduction of inflammation. This review explores how dietary fiber modulates the gut microbiota composition and function leading to the alteration of host physiology. High-fiber dietary regime has been consistently shown to increase the microbiome alpha diversity and short-chain fatty acids (SCFAs)-producing bacteria in the human gut. SCFAs are the main players in the interplay between diet, microbiota, and host health. In clinical settings, therapies with high fiber or SCFAs supplementations are proposed for inflammatory diseases. However, due to greater variations in the dosage, types, and durations of dietary fiber intervention in different clinical trials, the effect is controversial. Unraveling the mechanisms exerted by dietary fiber in synergy with the gut microbiome in human pathophysiology holds a promising prospect in guiding next-generation precision therapies.
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Background Statins have been widely used to prevent cardiovascular disease in middle-aged and elderly populations; however, the effect of long-term treatment on cognitive function is controversial. To simulate clinical conditions, middle-aged rats were given atorvastatin for 9 consecutive months to investigate the effect on natural cognitive decline and the possible mechanisms. Results The results showed that compared with the control group, long-term atorvastatin treatment naturally improved cognitive decline. Furthermore, long-term treatment regulated intestinal retinoic acid (RA) metabolism and storage by altering retinol dehydrogenase 7 (Rdh7) expression in the intestine, while RA metabolism affected the proliferation of intestinal T reg cells and inhibited IL-17 ⁺ γδ T-cell function. In addition, long-term atorvastatin increased intestinal flora richness and decreased IL-17 expression in hippocampal tissue. Conclusion Collectively, these findings provide the first evidence that long-term atorvastatin intervention may prevent cognitive decline in naturally ageing rats by inhibiting neuroinflammation via the gut-brain axis.
Article
The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.
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Combined oral contraceptives (containing synthetic forms of estradiol and progestins) are one of the most commonly used drugs among females. However, their effects on the gut-brain axis have not been investigated to a great extent despite clear evidence that suggest bi-directional interactions between the gut microbiome and endogenous sex hormones. Moreover, oral contraceptives are prescribed during adolescence, a critical period of development during which several brain structures and systems, such as hypothalamic-pituitary-gonadal axis, undergo maturation. Considering that oral contraceptives could impact the developing adolescent brain and that these effects may be mediated by the gut-brain axis, further research investigating the effects of oral contraceptives on the gut-brain axis is imperative. This article briefly reviews evidence from animal and human studies on the effects of combined oral contraceptives on the brain and the gut microbiota particularly during adolescence.
Chapter
The most popular approach to measure key functions of any living entity is to remove it and then study the consequences of its removal. Microorganisms influence their host in several manners and their role can be studied by eliminating them from their host and observe the host’s response, in their absence. Numerous studies have justified the vital role of microbiota in human health and disease development. Germ-free (GF) animal models are useful tools to improve our understanding of the host–microbiota relationship in vivo. Although different animal models, lacking microbiota (partially or completely) have been extensively used in research but germ-free (GF) mice are the most widely used rodent model in human research due to its close proximity to humans. In modern research, GF technology is one of the most attractive and informative tools for getting insights into host’s microbial community. Each body part harbors unique microorganisms with unique functions. Because of the advancement of microbial characterization techniques, the human microbiota community is expanding day by day. GF mice model can efficiently reveal the role of these valuable partners of humans. In spite of its high cost and obligation of skilled experts, GF research is a hot field for investigators and has a huge possibility for future applications. The present book chapter is a summary of the basics of GF technology and its main applications with future prospects.
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Early-life stress (ELS) leads to increased vulnerability to develop mental and metabolic disorders; however, the biological mechanisms leading to such programming are not fully clear. Increased attention has been given to the importance of the gut microbiota as a determinant of long-term health and as a potential target for noninvasive nutritional strategies to protect against the negative impact of ELS.
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Widespread contamination of soil, dust, and food with toxic metal(loid)s pose a significant public health concern. Only a portion of orally ingested metal(loid) contaminants are bioavailable, which is defined as the fraction of ingested metal(loid)s absorbed across the gastrointestinal barrier and into systemic circulation. Bioaccessibility tools are a class of in vitro assays used as a surrogate to estimate risk of oral exposure and bioavailability. Although development and use of bioaccessibility tools have contributed to our understanding of the factors influencing oral bioavailability of metal(loid)s, some of these assays may lack data that support their use in decisions concerning adverse health risks and soil remediation. This review discusses the factors known to influence bioaccessibility of metal(loid) contaminants and evaluates experimental approaches and key findings of SW-846 Test Method 1340, Unified BARGE Method, Simulated Human Intestinal Microbial Ecosystem, Solubility Bioaccessibility Research Consortium assay, In Vitro Gastrointestinal model, TNO-Gastrointestinal Model, and Dutch National Institute for Public Health and the Environment bioaccessibility models which are used to assess oral absolute bioavailability and relative bioavailability in solid matrices. The aim of this review was to identify emerging knowledge gaps and research needs with an emphasis on research required to evaluate these models on (1) standardization of assay techniques and methodology, and (2) use of common criteria for assessing the performance of bioaccessibility models.
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This review provides an overview of the interrelationships among the diet, gut microbiota and health status, and then focuses specifically on published research assessing the relationship of low/no-calorie sweeteners (LNCS) to selected aspects of the gut microbiota. Microbiome research is expanding as new data on its role in health and disease vulnerability emerge. The gut microbiome affects health, digestion, and susceptibility to disease. In the last 10 years, investigations of LNCS effects on the gut microbiota have proliferated, though results are conflicting and are often confounded by differences in study design such as study diet, the form of the test article, dosage, and study population. Staying current on microbiome research and the role of dietary inputs, like LNCS, will allow healthcare and nutrition practitioners to provide evidenced-based guidance to the individuals they serve.
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Background Human gut microbiota dysbiosis has been linked to a higher risk of non-communicable diseases (NCDs) such us inflammatory disorders, allergy and obesity. Specific dietary strategies, including the use of specific food supplements targeted to microbiota modulation, have been suggested to be especially relevant in reducing the risk of NCDs. In this regard, marine environment is considered as a pivotal source of nutrients and bioactive compounds such as polyunsaturated fatty acids, polysaccharides and active peptides. These compounds, including algae- (alginate, fucoidan) and animal-derived polysaccharides (chitin, chitosan), among others, have been widely studied. The use of these active substances from marine organisms as a food supplements has been reported to affect human health. Scope and approach This review provides the evidence-base information on the potential effects of various active substances from marine organisms, including fatty acids, proteins and polysaccharides, on the structure of gut microbiota and their effects on host health. Key findings and conclusions These compounds could regulate the gut microbiota structure and thus, intestinal and systemic level with potential human health benefits. The exploration and evaluation of the relationship between these substances and gut microbiota may provide a new direction for further exploration of the influence of high-added-value components on gut microbiota with potential health effects. These high-added-value compounds have been explored to not only improve the utilization rate of aquatic products, but also reduce waste and contribute to the environment and economy sustainability. Meanwhile, it is possible to expand the commercial applications of these products by the industry.
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Stroke is a multifactorial pathological condition caused by the formation of a clot, which decreases blood flow to the brain. The pathophysiology of stroke involves overstimulation of NMDA receptors, influx of calcium, and activation of PLA2, COX-2, iNOS, and various protein kinases leading to induction of excitotoxicity, oxidative stress, acute inflammation, and disruption of blood-brain and intestinal barriers. In addition, stroke-mediated brain injury is accompanied by alterations in gut microbiota, intestinal dysfunction, and disruption of the brain-gut axis leading to dysbiosis, leaky gut, and metabolic and immunological changes.
Article
Background and aims Many forms of immune dysregulation, which lead to inflammaging and senescence, have been demonstrated in patients with systemic lupus erythematosus (SLE; lupus) and in the aging population. The discovery of the microbiome and its association with human health and pathology has led it to be the center of investigation as a major contributor to the pathogenesis of immunosenescence in both populations. Similar alterations to the microbiome in the form of dysbiosis, that are demonstrated in both aging and in lupus patients, may help explain the significant overlap in clinical manifestations seen in these groups. Methods We performed an extensive literature review, utilizing the Pubmed search engine and Google Scholar for studies evaluating the microbiome in two groups, elderly populations and lupus patients (both murine and human models), between the years 2000–2019. We searched for the terms: microbiome, dysbiosis, lupus, elderly, aging and inflammaging, which yielded hundreds of articles, of which 114 were used for preparation of this paper. We compared the similarities between the populations. Results We found that the similar processes of immune dysregulation, in both aging populations and lupus patients, extend to the microbiome, in the form of dysbiosis. Some of these similarities include loss of microbiota biodiversity, increased representation of microbes that are associated with inflammation and disease (i.e Proteobacteria, Bacteroidetes), a relative decrease in protective microbes with “anti-inflammatory” properties (i.e Firmicutes) and a subsequent compromise to the intestinal barrier, leading to leakage of proinflammatory microbial components in both groups. Conclusions We conclude that there are several similar alterations in the composition and function of the microbiome of lupus patients and aging individuals, leading to immunosenescence, which may also be a contributing mechanism in lupus. It seems in fact that the microbiome of SLE may actually be analogous to immunosenescence. This knowledge may help the continuous efforts in finding a solution for both conditions.
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In the last few years, researchers are going beyond the conventional theories behind neuropsychiatric diseases, and the role of neuroinflammation is being increasingly recognized. It is known that microbiota plays a key role on human health and that there is a reciprocal communication between brain and gut. Also, it has been proved that altered microbiota can lead to systemic and central inflammation by several ways. For all these reasons, it has been hypothesized that alterations in the gut microbiota and the subsequent malfunction of the microbiota-gut-brain axis (MGBA) may be involved in the pathogenesis of various neuropsychiatric diseases including bipolar disorder. In this chapter, we aim to (1) summarize the different mechanisms by which the gut microbiota may modulate brain functions, (2) expose the consequences of leaky gut and dysbiosis, (3) illustrate the impact of MGBA in bipolar disorder patients and their relatives, and (4) present future therapeutic approaches targeting this axis.
The symbiosis between the gut microbiota and the host has been identified as an integral part of normal human physiology and physiological development. Research in germ-free or gnotobiotic animals has demonstrated the importance of this symbiosis in immune, vascular, hepatic, respiratory and metabolic systems. Disruption of the microbiota can also contribute to disease, and the microbiota has been implicated in numerous intestinal and extra-intestinal pathologies including colorectal cancer. Interactions between host and microbiota can occur either directly or indirectly, via microbial-derived metabolites. In this chapter, we focus on two major products of microbial metabolism, short-chain fatty acids and bile acids, and their role in colorectal cancer. Short-chain fatty acids are the products of microbial fermentation of complex carbohydrates and confer protection against cancer risk, while bile acids are compounds which are endogenous to the host, but undergo microbial modification in the large intestine leading to alterations in their bioactivity. Lastly, we discuss the ability of microbial modulation to mediate cancer risk and the potential to harness this ability as a prophylactic or therapeutic treatment in colorectal cancer.
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Interspecies transmissions of viruses between animals and humans may result in unpredictable pathogenic potential and new transmissible diseases. This mechanism has recently been exemplified by the discovery of new pathogenic viruses, such as the novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic, Middle-East respiratory syndrome-coronavirus epidemic in Saudi Arabia, and the deadly outbreak of Ebola in West Africa. The. SARS-CoV-2 causes coronavirus disease-19 (COVID-19), which is having a massive global impact in terms of economic disruption, and, above all, human health. The disease is characterized by dry cough, fever, fatigue, myalgia, and dyspnea. Other symptoms include headache, sore throat, rhinorrhea, and gastrointestinal disorders. Pneumonia appears to be the most common and severe manifestation of the infection. Currently, there is no vaccine or specific drug for COVID-19. Further, the development of new antiviral requires a considerable length of time and effort for drug design and validation. Therefore, repurposing the use of natural compounds can provide alternatives and can support therapy against COVID-19. In this review, we comprehensively discuss the prophylactic and supportive therapeutic role of probiotics for the management of COVID-19. In addition, the unique role of probiotics to modulate the gut microbe and assert gut homeostasis and production of interferon as an antiviral mechanism is described. Further, the regulatory role of probiotics on gut-lung axis and mucosal immune system for the potential antiviral mechanisms is reviewed and discussed. Key points • Gut microbiota role in antiviral diseases • Factors influencing the antiviral mechanism • Probiotics and Covid-19
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Background The microbiota, essential oils, and diet have been shown to interact with one another in ways that influence weight control. Scope and approach The review focus on gut microbiota, essential oils, and diet for weight control, (1) specifically addressing the role of diet on gut microbiota in weight control, (2) to assess the effectiveness of essential oils in the diet in weight control, (3) discussing the interconnections and implications of gut microbiota, essential oils, and diet in weight control. Key findings and conclusions The effects of essential oils on gut microbiota and weight management are rather complex similar to the case with many other natural products. Essential oils are effective in weight control by affecting microbiota and various molecular targets. Changing the gut microbiota by diet and inclusion of essential oils to balance its composition can be a promising approach for weight control.
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Diarrhea caused by Enterotoxigenic Escherichia coli (ETEC) is one of the most common clinical diseases observed in captive wild boars, is usually caused by an imbalance in the gut microbiome, and is responsible for piglets significant mortality. However, little research has been undertaken into the structure and function of the intestinal microbial communities in wild boar with diarrhea influenced by enterotoxigenic E. coli. In this study, fecal samples were collected and 16S-rRNA gene sequencing was used to compare the intestinal microbiome of healthy captive wild boar and wild boar with diarrhea on the same farm. We found that the intestinal microbial diversity of healthy wild boar (HWB) was relatively high, while that of diarrheic wild boar (DWB) was significantly lower. Line Discriminant Analysis Effect Size showed that at the genus level, the abundance of Escherichia-Shigella and Fusobacterium was significantly higher in DWB. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that the expression of genes in pathways including infectious diseases: bacterial, metabolism of amino acids, membrane transport, and signal transduction was significantly higher in DWB. In summary, this study provides a theoretical basis for the design of appropriate means of diarrhea treatment in captive wild boar.
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Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.
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Abstract The bacterial species diversity of three colonic tissue samples from elderly people was investigated by sequence analysis of randomly cloned eubacterial 16S rDNA. The majority of sequences (87%) clustered within three bacterial groups: (1) Bacteroides; (2) low G+C content Gram-positives related to Clostridium coccoides (cluster XIVa); (3) Gram-positives related to Clostridium leptum (cluster IV). These groups have been shown to dominate the human faecal flora. Only 25% of sequences were closely related (>97%) to current species type strains, and 28% were less than 97% related to any database entry. 19% of sequences were most closely related to recently isolated butyrate-producing bacteria belonging to clusters XIVa and IV, with a further 18% of the sequences most closely related to Ruminococcus obeum and Ruminococcus torques (members of cluster XIVa). These results provide the first molecular information on the microbial diversity present in human colonic samples.
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Ageing has been suggested to cause changes in the intestinal microbial community. In the present study, the microbiota of a previously well-defined group of elderly subjects aged between 70 and 85 years, both non-steroidal anti-inflammatory drugs (NSAID) users (n 9) and non-users (n 9), were further compared with young adults (n 14) with a mean age of 28 years, by two DNA-based techniques: percentage guanine+cytosine (%G+C) profiling and 16S rDNA sequencing. Remarkable changes in microbiota were described with both methods: compared with young adults a significant reduction in overall numbers of microbes in both elderly groups was measured. Moreover, the total number of microbes in elderly NSAID users was higher than in elderly without NSAID. In 16S rDNA sequencing, shifts in all major microbial phyla, such as lower numbers of Firmicutes and an increase in numbers of Bacteroidetes in the elderly were monitored. On the genus level an interesting link between reductions in the proportion of known butyrate producers belonging to Clostridium cluster XIVa, such as Roseburia and Ruminococcus, could be demonstrated in the elderly. Moreover, in the Actinobacteria group, lower numbers of Collinsella spp. were evident in the elderly subjects with NSAID compared both with young adults and the elderly without NSAID, suggesting that the use of NSAID along with age may also influence the composition of intestinal microbiota. Furthermore, relatively high numbers of Lactobacillus appeared only in the elderly subjects without NSAID. In general, the lowered numbers of microbial members in the major phyla, Firmicutes, together with changes in the epithelial layer functions can have a significant effect on the colon health of the elderly.
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Variations in the composition of the human intestinal microbiota are linked to diverse health conditions. High-throughput molecular technologies have recently elucidated microbial community structure at much higher resolution than was previously possible. Here we compare two such methods, pyrosequencing and a phylogenetic array, and evaluate classifications based on two variable 16S rRNA gene regions. Over 1.75 million amplicon sequences were generated from the V4 and V6 regions of 16S rRNA genes in bacterial DNA extracted from four fecal samples of elderly individuals. The phylotype richness, for individual samples, was 1,400-1,800 for V4 reads and 12,500 for V6 reads, and 5,200 unique phylotypes when combining V4 reads from all samples. The RDP-classifier was more efficient for the V4 than for the far less conserved and shorter V6 region, but differences in community structure also affected efficiency. Even when analyzing only 20% of the reads, the majority of the microbial diversity was captured in two samples tested. DNA from the four samples was hybridized against the Human Intestinal Tract (HIT) Chip, a phylogenetic microarray for community profiling. Comparison of clustering of genus counts from pyrosequencing and HITChip data revealed highly similar profiles. Furthermore, correlations of sequence abundance and hybridization signal intensities were very high for lower-order ranks, but lower at family-level, which was probably due to ambiguous taxonomic groupings. The RDP-classifier consistently assigned most V4 sequences from human intestinal samples down to genus-level with good accuracy and speed. This is the deepest sequencing of single gastrointestinal samples reported to date, but microbial richness levels have still not leveled out. A majority of these diversities can also be captured with five times lower sampling-depth. HITChip hybridizations and resulting community profiles correlate well with pyrosequencing-based compositions, especially for lower-order ranks, indicating high robustness of both approaches. However, incompatible grouping schemes make exact comparison difficult.
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The paradox of a host specificity of the human faecal microbiota otherwise acknowledged as characterized by global functionalities conserved between humans led us to explore the existence of a phylogenetic core. We investigated the presence of a set of bacterial molecular species that would be altogether dominant and prevalent within the faecal microbiota of healthy humans. A total of 10 456 non-chimeric bacterial 16S rRNA sequences were obtained after cloning of PCR-amplified rDNA from 17 human faecal DNA samples. Using alignment or tetranucleotide frequency-based methods, 3180 operational taxonomic units (OTUs) were detected. The 16S rRNA sequences mainly belonged to the phyla Firmicutes (79.4%), Bacteroidetes (16.9%), Actinobacteria (2.5%), Proteobacteria (1%) and Verrumicrobia (0.1%). Interestingly, while most of OTUs appeared individual-specific, 2.1% were present in more than 50% of the samples and accounted for 35.8% of the total sequences. These 66 dominant and prevalent OTUs included members of the genera Faecalibacterium, Ruminococcus, Eubacterium, Dorea, Bacteroides, Alistipes and Bifidobacterium. Furthermore, 24 OTUs had cultured type strains representatives which should be subjected to genome sequence with a high degree of priority. Strikingly, 52 of these 66 OTUs were detected in at least three out of four recently published human faecal microbiota data sets, obtained with very different experimental procedures. A statistical model confirmed these OTUs prevalence. Despite the species richness and a high individual specificity, a limited number of OTUs is shared among individuals and might represent the phylogenetic core of the human intestinal microbiota. Its role in human health deserves further study.
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In humans, the intestinal microbiota plays an important role in the maintenance of host health by providing energy, nutrients, and immunological protection. Applying current molecular methods is necessary to surmount the limitations of classical culturing techniques in order to obtain an accurate description of the microbiota composition. Here we report on the comparative assessment of human fecal microbiota from three age-groups: infants, adults and the elderly. We demonstrate that the human intestinal microbiota undergoes maturation from birth to adulthood and is further altered with ageing. The counts of major bacterial groups Clostridium leptum, Clostridium coccoides, Bacteroidetes, Bifidobacterium, Lactobacillus and Escherichia coli were assessed by quantitative PCR (qPCR). By comparing species diversity profiles, we observed age-related changes in the human fecal microbiota. The microbiota of infants was generally characterized by low levels of total bacteria. C. leptum and C. coccoides species were highly represented in the microbiota of infants, while elderly subjects exhibited high levels of E. coli and Bacteroidetes. We observed that the ratio of Firmicutes to Bacteroidetes evolves during different life stages. For infants, adults and elderly individuals we measured ratios of 0.4, 10.9 and 0.6, respectively. In this work we have confirmed that qPCR is a powerful technique in studying the diverse and complex fecal microbiota. Our work demonstrates that the fecal microbiota composition evolves throughout life, from early childhood to old age.
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In this paper we present the in silico assessment of the diversity of variable regions of the small subunit ribosomal RNA (SSU rRNA) gene based on an ecosystem-specific curated database, describe a probe design procedure based on two hypervariable regions with minimal redundancy and test the potential of such probe design strategy for the design of a flexible microarray platform. This resulted in the development and application of a phylogenetic microarray for studying the human gastrointestinal microbiota--referred as the human intestinal tract chip (HITChip). Over 4800 dedicated tiling oligonucleotide probes were designed based on two hypervariable regions of the SSU rRNA gene of 1140 unique microbial phylotypes (< 98% identity) following analysis of over 16,000 human intestinal SSU rRNA sequences. These HITChip probes were hybridized to a diverse set of human intestinal samples and SSU rRNA clones to validate its fingerprinting and quantification potential. Excellent reproducibility (median Pearson's correlation of 0.99) was obtained following hybridization with T7 polymerase transcripts generated in vitro from SSU rRNA gene amplicons. A linear dose-response was observed with artificial mixtures of 40 different representative amplicons with relative abundances as low as 0.1% of total microbiota. Analysis of three consecutively collected faecal samples from ten individuals (five young and five elderly adults) revealed temporal dynamics and confirmed that the adult intestinal microbiota is an individual-specific and relatively stable ecosystem. Further analysis of the stable part allowed for the identification of a universal microbiota core at the approximate genus level (90% sequence similarity). This core consists of members of Actinobacteria, Bacteroidetes and Firmicutes. Used as a phylogenetic fingerprinting tool with the possibility for relative quantification, the HITChip has the potential to bridge the gaps in our knowledge in the quantitative and qualitative description of the human gastrointestinal microbiota composition.
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The human intestinal tract harbors a complex microbial ecosystem which plays a key role in nutrition and health. Although this microbiota has been studied in great detail by culture techniques, microscopic counts on human feces suggest that 60 to 80% of the observable bacteria cannot be cultivated. Using comparative analysis of cloned 16S rRNA gene (rDNA) sequences, we have investigated the bacterial diversity (both cultivated and noncultivated bacteria) within an adult-male fecal sample. The 284 clones obtained from 10-cycle PCR were classified into 82 molecular species (at least 98% similarity). Three phylogenetic groups contained 95% of the clones: the Bacteroides group, the Clostridium coccoides group, and the Clostridium leptum subgroup. The remaining clones were distributed among a variety of phylogenetic clusters. Only 24% of the molecular species recovered corresponded to described organisms (those whose sequences were available in public databases), and all of these were established members of the dominant human fecal flora (e.g., Bacteroides thetaiotaomicron, Fusobacterium prausnitzii, and Eubacterium rectale). However, the majority of generated rDNA sequences (76%) did not correspond to known organisms and clearly derived from hitherto unknown species within this human gut microflora.
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This study aimed at determining ageing-related shifts in diversity and composition of key members of the fecal microbiota by comparing institutionalized elderly (n = 17, 78-94 years) and young volunteers (n = 17, 18-31 years). A combination of molecular methods was used to characterize the diversity and relative abundance of total gastro-intestinal flora, along with relevant subsets within the genera Bacteroides, bifidobacteria and Clostridium cluster IV. The institutionalized elderly harbored significantly higher numbers of Bacteroides cells than control (28.5 +/- 8.6%; 21.4 +/- 7.7%; p = 0.016) but contained less bifidobacteria (1.3 +/- 0.9, 2.7 +/- 3.2%, p = 0.026) and Clostridium cluster IV (26.9 +/- 11.7%, 36.36 +/- 11.26%, p = 0.036). The elderly also displayed less total Bacteria diversity and less diversity with the Clostridium cluster IV (p < 0.016) and Bacteroides. Despite high individual variations, our analyses indicate the composition of microbiota in the elderly comprises a less diverse subset of young healthy microbiota. A better understanding of the individual composition of the human microbiota and the effects of ageing might result in the development of specifically targeted supplementation for elderly citizens in order to support healthy ageing.
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Recent reports suggest that the metabolic activity of the gut microbiota may contribute to the pathogenesis of obesity and hepatic steatosis. The objective was to determine whether the fat composition of host tissues might be influenced by oral administration of commensal bifidobacteria previously shown by us to produce bioactive isomers of conjugated linoleic acid (CLA). Murine trials were conducted in which linoleic acid-supplemented diets were fed with or without Bifidobacterium breve NCIMB 702258 (daily dose of 10(9) microorganisms) to healthy BALB/c mice and to severe combined immunodeficient mice for 8-10 wk. To ensure that the observations were not peculiar to mice, a similar trial was conducted in weanling pigs over 21 d. Tissue fatty acid composition was assessed by gas-liquid chromatography. In comparison with controls, there was an increase in cis-9, trans-11 CLA in the livers of the mice and pigs after feeding with linoleic acid in combination with B. breve NCIMB 702258 (P < 0.05). In addition, an altered profile of polyunsaturated fatty acid composition was observed, including higher concentrations of the omega-3 (n-3) fatty acids eicosapentaenoic acid and docosahexaenoic acid in adipose tissue (P < 0.05). These changes were associated with reductions in the proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma (P < 0.05). These results are consistent with the concept that the metabolome is a composite of host and microbe metabolic activity and that the influence of the microbiota on host fatty acid composition can be manipulated by oral administration of CLA-producing microorganisms.
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Probiotics have a range of proposed health benefits for the consumer, which may include modulating the levels of beneficial elements in the microbiota. Recent investigations using molecular approaches have revealed a human intestinal microbiota comprising over 1000 phylotypes. Mechanisms whereby probiotics impact on the intestinal microbiota include competition for substrates, direct antagonism by inhibitory substances, competitive exclusion, and potentially host-mediated effects such as improved barrier function and altered immune response. We now have the microbial inventories and genetic blueprints to begin tackling intestinal microbial ecology at an unprecedented level of detail, aided by the understanding that dietary components may be utilized differentially by individual phylotypes. Controlled intervention studies in humans, utilizing latest molecular technologies, are required to consolidate evidence for bacterial species that impact on the microbiota. Mechanistic insights should be provided by metabolomics and other analytical techniques for small molecules. Rigorous characterization of interactions between the diet, microbiota, and probiotic bacteria will provide new opportunities for modulating the microbiota towards improving human health.
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Gut Bifidobacterium microbiota of the elderly has been suggested to differ from that of adults, possibly promoting the risk of infections and gut barrier dysfunction. Specific probiotics may improve the gut barrier. In this randomized, placebo-controlled intervention study, 66 elders consumed a fermented oat drink containing probiotic Bifidobacterium longum 46 and B. longum 2C or a non-fermented placebo oat drink for 6 months. Faecal samples were collected before, during and after the intervention. Levels of faecal bifidobacteria were determined using species-specific quantitative PCR and plate counting. The Bifidobacterium levels in the elderly were high and the species composition diverse. Probiotic intervention increased the levels bifidobacteria significantly. Specifically, the levels of B. catenulatum, B. bifidum and B. breve were enhanced. Consumption of the fermented oat drink itself was also associated with certain changes in microbiota. In conclusion, Bifidobacterium microbiota of elderly subjects may be modulated by probiotic administration. In some healthy elderly populations, Bifidobacterium microbiota may be more abundant and diverse than previously suggested.
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Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the Bacteria in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically, Firmicutes were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of Gammaproteobacteria. Numbers of the H(2)-producing Prevotellaceae were highly enriched in the obese individuals. Unlike the highly diverse Bacteria, the Archaea comprised mainly members of the order Methanobacteriales, which are H(2)-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H(2)-utilizing methanogenic Archaea in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H(2)-producing bacteria with relatively high numbers of H(2)-utilizing methanogenic Archaea in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H(2) transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.
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The objective of this work was to elucidate if breast milk contains bifidobacteria and whether they can be transmitted to the infant gut through breastfeeding. Twenty-three women and their respective infants provided samples of breast milk and feces, respectively, at days 4 to 7 after birth. Gram-positive and catalase-negative isolates from specific media with typical bifidobacterial shapes were identified to the genus level by F6PPK (fructose-6-phosphate phosphoketolase) assays and to the species level by 16S rRNA gene sequencing. Bifidobacterial communities in breast milk were assessed by PCR-denaturing gradient gel electrophoresis (PCR-DGGE), and their levels were estimated by quantitative real-time PCR (qRTi-PCR). Bifidobacteria were present in 8 milk samples and 21 fecal samples. Bifidobacterium breve, B. adolescentis, and B. bifidum were isolated from milk samples, while infant feces also contained B. longum and B. pseudocatenulatum. PCR-DGGE revealed the presence of one to four dominant bifidobacterial bands in 22 milk samples. Sequences with similarities above 98% were identified as Bifidobacterium breve, B. adolescentis, B. longum, B. bifidum, and B. dentium. Bifidobacterial DNA was detected by qRTi-PCR in the same 22 milk samples at a range between 40 and 10,000 16S rRNA gene copies per ml. In conclusion, human milk seems to be a source of living bifidobacteria for the infant gut.
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The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).
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Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. Accordingly, the complete genome sequence of Bifidobacterium longum subsp. infantis ATCC15697 reflects a competitive nutrient-utilization strategy targeting milk-borne molecules which lack a nutritive value to the neonate. Several chromosomal loci reflect potential adaptation to the infant host including a 43 kbp cluster encoding catabolic genes, extracellular solute binding proteins and permeases predicted to be active on milk oligosaccharides. An examination of in vivo metabolism has detected the hallmarks of milk oligosaccharide utilization via the central fermentative pathway using metabolomic and proteomic approaches. Finally, conservation of gene clusters in multiple isolates corroborates the genomic mechanism underlying milk utilization for this infant-associated phylotype. • carbohydrate metabolism • co-evolution • genomics • human milk oligosaccharides
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The human body is colonized by an enormous population of bacteria (microbiota) that provides the host with coding capacity and metabolic activities. Among the human gut microbiota are health-promoting indigenous species (probiotic bacteria) that are commonly consumed as live dietary supplements. Recent genomics-based studies (probiogenomics) are starting to provide insights into how probiotic bacteria sense and adapt to the gastrointestinal tract environment. In this Review, we discuss the application of probiogenomics in the elucidation of the molecular basis of probiosis using the well-recognized model probiotic bacteria genera Bifidobacterium and Lactobacillus as examples.
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The human intestinal microbiota is essential to the health of the host and plays a role in nutrition, development, metabolism, pathogen resistance, and regulation of immune responses. Antibiotics may disrupt these coevolved interactions, leading to acute or chronic disease in some individuals. Our understanding of antibiotic-associated disturbance of the microbiota has been limited by the poor sensitivity, inadequate resolution, and significant cost of current research methods. The use of pyrosequencing technology to generate large numbers of 16S rDNA sequence tags circumvents these limitations and has been shown to reveal previously unexplored aspects of the "rare biosphere." We investigated the distal gut bacterial communities of three healthy humans before and after treatment with ciprofloxacin, obtaining more than 7,000 full-length rRNA sequences and over 900,000 pyrosequencing reads from two hypervariable regions of the rRNA gene. A companion paper in PLoS Genetics (see Huse et al., doi: 10.1371/journal.pgen.1000255) shows that the taxonomic information obtained with these methods is concordant. Pyrosequencing of the V6 and V3 variable regions identified 3,300-5,700 taxa that collectively accounted for over 99% of the variable region sequence tags that could be obtained from these samples. Ciprofloxacin treatment influenced the abundance of about a third of the bacterial taxa in the gut, decreasing the taxonomic richness, diversity, and evenness of the community. However, the magnitude of this effect varied among individuals, and some taxa showed interindividual variation in the response to ciprofloxacin. While differences of community composition between individuals were the largest source of variability between samples, we found that two unrelated individuals shared a surprising degree of community similarity. In all three individuals, the taxonomic composition of the community closely resembled its pretreatment state by 4 weeks after the end of treatment, but several taxa failed to recover within 6 months. These pervasive effects of ciprofloxacin on community composition contrast with the reports by participants of normal intestinal function and with prior assumptions of only modest effects of ciprofloxacin on the intestinal microbiota. These observations support the hypothesis of functional redundancy in the human gut microbiota. The rapid return to the pretreatment community composition is indicative of factors promoting community resilience, the nature of which deserves future investigation.
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A decrease in the abundance and biodiversity of intestinal bacteria within the dominant phylum Firmicutes has been observed repeatedly in Crohn disease (CD) patients. In this study, we determined the composition of the mucosa-associated microbiota of CD patients at the time of surgical resection and 6 months later using FISH analysis. We found that a reduction of a major member of Firmicutes, Faecalibacterium prausnitzii, is associated with a higher risk of postoperative recurrence of ileal CD. A lower proportion of F. prausnitzii on resected ileal Crohn mucosa also was associated with endoscopic recurrence at 6 months. To evaluate the immunomodulatory properties of F. prausnitzii we analyzed the anti-inflammatory effects of F. prausnitzii in both in vitro (cellular models) and in vivo [2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced] colitis in mice. In Caco-2 cells transfected with a reporter gene for NF-κB activity, F. prausnitzii had no effect on IL-1β-induced NF-κB activity, whereas the supernatant abolished it. In vitro peripheral blood mononuclear cell stimulation by F. prausnitzii led to significantly lower IL-12 and IFN-γ production levels and higher secretion of IL-10. Oral administration of either live F. prausnitzii or its supernatant markedly reduced the severity of TNBS colitis and tended to correct the dysbiosis associated with TNBS colitis, as demonstrated by real-time quantitative PCR (qPCR) analysis. F. prausnitzii exhibits anti-inflammatory effects on cellular and TNBS colitis models, partly due to secreted metabolites able to block NF-κB activation and IL-8 production. These results suggest that counterbalancing dysbiosis using F. prausnitzii as a probiotic is a promising strategy in CD treatment. • IBD • microbiota • probiotic
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The frequent discrepancy between direct microscopic counts and numbers of culturable bacteria from environmental samples is just one of several indications that we currently know only a minor part of the diversity of microorganisms in nature. A combination of direct retrieval of rRNA sequences and whole-cell oligonucleotide probing can be used to detect specific rRNA sequences of uncultured bacteria in natural samples and to microscopically identify individual cells. Studies have been performed with microbial assemblages of various complexities ranging from simple two-component bacterial endosymbiotic associations to multispecies enrichments containing magnetotactic bacteria to highly complex marine and soil communities. Phylogenetic analysis of the retrieved rRNA sequence of an uncultured microorganism reveals its closest culturable relatives and may, together with information on the physicochemical conditions of its natural habitat, facilitate more directed cultivation attempts. For the analysis of complex communities such as multispecies biofilms and activated-sludge flocs, a different approach has proven advantageous. Sets of probes specific to different taxonomic levels are applied consecutively beginning with the more general and ending with the more specific (a hierarchical top-to-bottom approach), thereby generating increasingly precise information on the structure of the community. Not only do rRNA-targeted whole-cell hybridizations yield data on cell morphology, specific cell counts, and in situ distributions of defined phylogenetic groups, but also the strength of the hybridization signal reflects the cellular rRNA content of individual cells. From the signal strength conferred by a specific probe, in situ growth rates and activities of individual cells might be estimated for known species. In many ecosystems, low cellular rRNA content and/or limited cell permeability, combined with background fluorescence, hinders in situ identification of autochthonous populations. Approaches to circumvent these problems are discussed in detail.