Prepare a technical article that describes how the particular “gut health promoting” food/supplement you ate for three days could have affected your gut microbiome. Prepare this article as if it is intended for a chapter in a review book for the RD exam (or for your own review), or a reading assignment in a review/refresher course for health care professionals who took A&P long time ago. Divide your article into sections with headings. Provide a short and interesting title.
untitled Review Article Introduction to the human gut microbiota Elizabeth Thursby and Nathalie Juge The Gut Health and Food Safety Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, U.K. Correspondence: Nathalie Juge (
[email protected]) The human gastrointestinal (GI) tract harbours a complex and dynamic population of microorganisms, the gut microbiota, which exert a marked influence on the host during homeostasis and disease. Multiple factors contribute to the establishment of the human gut microbiota during infancy. Diet is considered as one of the main drivers in shaping the gut microbiota across the life time. Intestinal bacteria play a crucial role in maintaining immune and metabolic homeostasis and protecting against pathogens. Altered gut bac- terial composition (dysbiosis) has been associated with the pathogenesis of many inflam- matory diseases and infections. The interpretation of these studies relies on a better understanding of inter-individual variations, heterogeneity of bacterial communities along and across the GI tract, functional redundancy and the need to distinguish cause from effect in states of dysbiosis. This review summarises our current understanding of the development and composition of the human GI microbiota, and its impact on gut integrity and host health, underlying the need for mechanistic studies focusing on host–microbe interactions. Introduction The human gastrointestinal (GI) tract represents one of the largest interfaces (250–400 m2) between the host, environmental factors and antigens in the human body. In an average life time, around 60 tonnes of food pass through the human GI tract, along with an abundance of microorganisms from the environment which impose a huge threat on gut integrity [1]. The collection of bacteria, archaea and eukarya colonising the GI tract is termed the ‘gut microbiota’ and has co-evolved with the host over thousands of years to form an intricate and mutually beneficial relationship [2,3]. The number of microorganisms inhabiting the GI tract has been estimated to exceed 1014, which encom- passes ∼10 times more bacterial cells than the number of human cells and over 100 times the amount of genomic content (microbiome) as the human genome [2,4]. However, a recently revised estimate has suggested that the ratio of human:bacterial cells is actually closer to 1:1 [5]. As a result of the vast number of bacterial cells in the body, the host and the microorganisms inhabiting it are often referred to as a ‘superorganism’ [4,6]. The microbiota offers many benefits to the host, through a range of physiological functions such as strengthening gut integrity or shaping the intestinal epithelium [7], harvesting energy [8], protecting against pathogens [9] and regulating host immunity [10]. However, there is potential for these mechanisms to be disrupted as a result of an altered microbial composition, known as dysbiosis. With increasingly sophisticated methods to profile and characterise complex ecosystems being developed, a role for the microbiota in a large number of intestinal and extra-intestinal diseases has become steadily apparent [11,12]. This review summarises our current understanding of the development and compos- ition of the human GI microbiota, and its impact on gut integrity and host health. Composition and structure of the human GI microbiota Around a decade ago, most knowledge about the adult human gut microbiota stemmed from labour- intensive culture-based methods [13]. Recently, our ability to survey the breadth of the gut microbiota has greatly improved due to the advent of culture-independent approaches such as high-throughput and low-cost sequencing methods. Targeting of the bacterial 16S ribosomal RNA (rRNA) gene is a Version of Record published: 16 May 2017 Received: 24 October 2016 Revised: 3 March 2017 Accepted: 6 March 2017 © 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). 1823 Biochemical Journal (2017) 474 1823–1836 DOI: 10.1042/BCJ20160510 https://creativecommons.org/licenses/by/4.0 https://creativecommons.org/licenses/by/4.0 popular approach [14,15], since this gene is present in all bacteria and archaea and contains nine highly variable regions (V1–V9), which allows species to be easily distinguished. Former techniques concentrated on sequencing the entire 16S rRNA gene. In an early study using this method, the extreme insensitivity and bias of culturing methods were highlighted, since 76% of the rRNA sequences obtained from an adult male faecal sample belonged to novel and uncharacterised species [16]. Recently, the focus of 16S rRNA sequencing has shifted to analysing shorter subregions of the gene in greater depth [15]; however, the utilisation of shorter read lengths can introduce errors [14]. More reliable estimates of microbiota composition and diversity may be provided by whole-genome shotgun metagenomics due to the higher resolution and sensitivity of these techniques [14]. Combined data from the MetaHit and the Human Microbiome Project have provided the most comprehensive view of the human-associated microbial repertoire to date [17,18]. Compiled data from these studies identified 2172 species isolated from human beings, classified into 12 different phyla, of which 93.5% belonged to Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes. Three of the 12 identified phyla contained only one species isolated from humans, including an intestinal species, Akkermansia muciniphila, the only known repre- sentative of the Verrucomicrobia phyla. In humans, 386 of the identified species are strictly anaerobic and hence will generally be found in mucosal regions such as the oral cavity and the GI tract [17]. The gut microbiota is not as diverse as the microbial communities from some other bodily sites and reveals a high degree of functional redundancy [19–21]. An extensive catalogue of the functional capacity of the human gut microbiome was recently obtained, where 9 879 896 genes were identified through a combination of 249 newly sequenced and 1018 published samples [18]. The study identified the presence of country-specific microbial signatures, suggesting that gut microbiota composition is shaped by environmental factors, such as diet, and possibly also by host genetics [18]. However, it should also be noted that microbiotas that differ in terms of composition may share some degree of functional redundancy, yielding similar protein or metabolite profiles [22]. This information is crucial for developing therapeutic strategies to modify and shape the microbial community in disease. Development of the human GI microbiota The development of the microbiota is generally believed to begin from birth, although this dogma is challenged by a limited number of studies in which microbes were detected in womb tissues, such as the placenta [23,24]. After birth, the GI tract is rapidly colonised, with life events such as illness, antibiotic treatment and changes in diet causing chaotic shifts in the microbiota [24,25]. The mode of delivery also appears to affect the microbiota composition, with vaginally delivered infants’ microbiota containing a high abundance of lactobacilli during the first few days, a reflection of the high load of lactobacilli in the vaginal flora [26,27]. In contrast, the micro- biota of infants delivered by C-section is depleted and delayed in the colonisation of the Bacteroides genus, but colonised by facultative anaerobes such as Clostridium species [28,29]. Whilst the faecal microbiota of 72% of vaginally delivered infants resembles that of their mothers’ faecal microbiota, in babies delivered by C-section, this percentage is reduced to only 41% [30]. In early stages of development, the microbiota is generally low in diversity and is dominated by two main phyla, Actinobacteria and Proteobacteria [24,31]. During the first year of life, the microbial diversity increases and the microbiota composition converges towards a distinct adult-like microbial profile with temporal patterns that are unique to each infant [32]. By around 2.5 years of age, the composition, diversity and functional capabilities of the infant microbiota resemble those of adult microbiota [24,25]. Although, in adulthood, the composition of the gut microbiota is relatively stable, it is still subject to perturbation by life events [33]. In individuals over the age of 65, the microbial community shifts, with an increased abundance of Bacteroidetes phyla and Clostridium cluster IV, in contrast with younger subjects where cluster XIVa is more prevalent [34]. In contrast, a separate study observed that the microbiota of a young cohort and an elderly population (70 years) were relatively comparable, whilst the diversity of the microbiota from a cohort of centenarians was significantly reduced [35]. The centenarian microbiota also exhibited group- specific differences such as an increase in the abundance of facultative anaerobes (e.g. Escherichia coli) and rearrangement of the profile of butyrate producers (e.g. decrease in Faecalibacterium prausnitzii) [35]. In the elderly population, a significant relationship has been identified between diversity and living arrangements, such as community dwelling or long-term residential care [36]. Overall, the capacity of the microbiota to carry out metabolic processes such as short-chain fatty acid (SCFA) production and amylolysis is reduced in the elderly, whilst proteolytic activity is increased [37]. Given the increasing evidence for the role of SCFAs as key metabolic and immune mediators (as reviewed below), it was postulated that the decrease in SCFAs may nurture the inflamm-ageing process in the intestine of aged people [38]. 1824 © 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Biochemical Journal (2017) 474 1823–1836 DOI: 10.1042/BCJ20160510 https://creativecommons.org/licenses/by/4.0 Biogeography of the human microbiota in the GI tract Microbiota composition in the GI tract is reflective of the physiological properties in a given region and is stratified on both a transverse and longitudinal axis [39]. The density and composition of the microbiota are affected by chemical, nutritional and immunological gradients along the gut. In the small intestine, there are typically high levels of acids, oxygen and antimicrobials, and a short transit time [40]. These properties limit bacterial growth, such that only rapidly growing, facultative anaerobes with the ability to adhere to epithelia/ mucus are thought to survive [40]. In mice, the small-intestine microbial community is largely dominated by Lactobacillaceae [41]. In contrast, colonic conditions support a dense and diverse community of bacteria, mainly anaerobes with the ability to utilise complex carbohydrates which are undigested in the small intestine. In the colon Prevotellaceae, Lachnospiraceae and Rikenellaceae have been shown to dominate [40,41]. In contrast with the differing microbiota composition between varying GI organs, the microbiota of different colorectal mucosal regions within the same individual is spatially conserved in terms of both composition and diversity [42,43]. This feature is apparent even during periods of localised inflammation [43]. On the other hand, the faecal/luminal and mucosal compositions are significantly different [42,43]. For example, the abun- dance of Bacteroidetes appears to be higher in faecal/luminal samples than in the mucosa [42,44]. In contrast, Firmicutes, specifically Clostridium cluster XIVa, are enriched in the mucus layer compared with the lumen [44]. Interestingly, recent experiments in mice colonised with a diverse specific pathogen-free microbiota showed that the outer mucus of the large intestine forms a unique microbial niche and that bacterial species present in the mucus show differential proliferation and resource utilisation compared with the same species in the intestinal lumen [45]. These observations