Gut Online First, published on September 2, 2015 as 10.1136/gutjnl-2015-309990 Recent advances in basic science The gut microbiota and host health: a new clinical Gut: first published as 10.1136/gutjnl-2015-309990 on 2 September 2015. Downloaded from frontier Julian R Marchesi,1,2 David H Adams,3 Francesca Fava,4 Gerben D A Hermes,5,6 Gideon M Hirschfield,3 Georgina Hold,7 Mohammed Nabil Quraishi,3 James Kinross,8 Hauke Smidt,5 Kieran M Tuohy,4 Linda V Thomas,9 Erwin G Zoetendal,5,6 Ailsa Hart10 1School of Biosciences, ABSTRACT integrate an individual’s microbiota into some form Museum Avenue, Cardiff Over the last 10–15 years, our understanding of the of personalised healthcare and, by better under- University, Cardiff, UK ’ 2Centre for Digestive and Gut composition and functions of the human gut microbiota standing its role, treat an individual s diseases more Health, Imperial College has increased exponentially. To a large extent, this has efficiently and in a more targeted fashion. With a London, London, UK been due to new ‘omic’ technologies that have more complete understanding of the disease 3 NIHR Biomedical Research facilitated large-scale analysis of the genetic and process, we will be able to more accurately stratify Unit, Centre for Liver Research, metabolic profile of this microbial community, revealing different disease states and determine whether or University of Birmingham, fl Birmingham, UK it to be comparable in in uence to a new organ in the not the gut microbiota is a potential therapeutic 4Nutrition and Nutrigenomics body and offering the possibility of a new route for target which we can modulate in order to treat spe- Group, Department of Food therapeutic intervention. Moreover, it might be more cific diseases. Quality and Nutrition, Research accurate to think of it like an immune system: a This review gives a much needed update on and Innovation Centre, Trento, Italy collection of cells that work in unison with the host and current understanding of the gut microbiota in GI 5Laboratory of Microbiology, that can promote health but sometimes initiate disease. diseases and metabolic disorders, and gives an Wageningen University, This review gives an update on the current knowledge in insight into how this might impact on clinical prac- Wageningen, The Netherlands 6 the area of gut disorders, in particular metabolic tice. The evidence for the preventive and thera- Top Institute Food and syndrome and obesity-related disease, liver disease, IBD peutic benefit of different ways of modulating the Nutrition (TIFN), Wageningen, The Netherlands and colorectal cancer. The potential of manipulating the gut microbiota, such as probiotics, prebiotics, anti- 7Division of Applied Medicine, gut microbiota in these disorders is assessed, with an biotics and faecal microbiota transplantation (FMT) School of Medicine and examination of the latest and most relevant evidence (see box 2), is reviewed. Dentistry, University of relating to antibiotics, probiotics, prebiotics, polyphenols Aberdeen, Institute of Medical and faecal microbiota transplantation. Sciences, Aberdeen, UK CURRENT UNDERSTANDING OF THE GUT 8Section of Computational and Systems Medicine, Faculty of MICROBIOTA Medicine, Imperial College In the last decade, several large-scale projects, for London, London, UK INTRODUCTION example, the human microbiome project, have http://gut.bmj.com/ 9 Yakult UK Limited, Imagine the scenario: a scientist at a conference investigated the microbiota of a variety of bodily Middlesex, UK 10 ’ claims to have found a new organ in the human niches, including the skin as well as the oral, vaginal IBD Unit, St Mark s Hospital 2 and Imperial College London, body. It is comparable to the immune system in as and nasal cavities. While some of these are rela- London, UK much as it is made up of a collection of cells, it tively easy to access, the GI tract remains a challen- contains a 100 times more genes than the host, is ging environment to sample, and to describe. Correspondence to host-specific, contains heritable components, can be Currently the majority of research is focused on the Dr Ailsa Hart, IBD Unit, fi on September 27, 2021 by guest. Protected copyright. St Mark’s Hospital and modi ed by diet, surgery or antibiotics, and in its gut microbiota, since this is where the greatest Imperial College London, absence nearly all aspects of host physiology are density and numbers of bacteria are found, with Watford Road, London affected. While this may seem far-fetched, it is the most data being derived from faecal samples and, to HA13UJ, UK; current situation in which we find ourselves. We a lesser extent, mucosal biopsies. While it is rela- [email protected] now realise that the human microbiota is an over- tively easy to obtain fresh faecal samples, the infor- fi Received 20 May 2015 looked system that makes a signi cant contribution mation obtained from them does not represent the Revised 14 July 2015 to human biology and development. Moreover, complete picture within the gut. From a number of Accepted 16 July 2015 there is good evidence that humans co-evolved a limited studies, we know that the small intestine requirement for their microbiota.1 contains a very different abundance and compos- In the past decade, partly because of high reso- ition of bacteria, with much more dynamic variation lution observational studies using next-generation compared with the colon.3 The colonic microbiota sequencing technologies and metabolite profiling is largely driven by the efficient degradation of (see box 1), the gut microbiota has become asso- complex indigestible carbohydrates but that of the ciated with promotion of health and the initiation small intestine is shaped by its capacity for the fast or maintenance of different GI and non-GI dis- import and conversion of relatively small carbohy- eases. As we enter the postmetagenomic era, we drates, and rapid adaptation to overall nutrient need to move away from simple observations to availability. While faeces are not an ideal proxy for determine what are merely correlations and what the GI tract, they do give a snapshot of the diversity To cite: Marchesi JR, are causal links—and focus efforts and resources on within the large intestine. Furthermore, the majority Adams DH, Fava F, et al. Gut Published Online First: the latter. This postmetagenomic era is starting to of the data comes from North American and [please include Day Month provide new therapeutic targets based on a better European studies with very few studies in Asia, Year] doi:10.1136/gutjnl- understanding of how the microbiota interacts with Africa or South America. Hence we have a some- 2015-309990 the host’s physiology. Ultimately, we aim to what biased view of the gut microbiota. Marchesi JR, et al. Gut 2015;0:1–10. doi:10.1136/gutjnl-2015-309990 1 Copyright Article author (or their employer) 2015. Produced by BMJ Publishing Group Ltd (& BSG) under licence. Recent advances in basic science Box 1 A short primer of microbiology (see also Lepage Box 2 Potential therapies aimed at modulation of the Gut: first published as 10.1136/gutjnl-2015-309990 on 2 September 2015. Downloaded from et al)4 gut microbiota Dysbiosis Probiotics: Live microorganisms that, when administered in A disturbance or imbalance in a biological system, for example, adequate amounts, confer a health benefit on the host.107 108 changes in the types and numbers of bacteria in the gut which Examples include strains of the genera Bifidobacterium and may lead to developing different diseases, such as IBD. Lactobacillus. Probiotics can have multiple interactions with the Inflammasomes host,109 including competitive inhibition of other microbes, Recently discovered multiprotein complexes that are involved in effects on mucosal barrier function and interaction with antigen a wide range of inflammatory processes including programmed presenting dendritic cells.72 cell death (pyroptosis), in response to the recognition of Prebiotics: A selectively fermented ingredient that results in microbial and danger signals. specific changes in the composition and/or activity of the GI Lipopolysaccharide (LPS) microbiota, thus conferring benefit(s) upon host health.110 A major component of the outer membrane of Gram-negative Prebiotics are usually non-digestible carbohydrates, bacteria; an endotoxin. Now implicated as a driver of oligosaccharides or short polysaccharides, with inulin, inflammation and associated with onset of certain diseases. oligofructose, galactofructose, galacto-oligosaccharides and Lipoteichoic acid xylo-oligosaccharides being some of the most intensively A major component of the outer membrane of Gram-positive studied. bacteria; an endotoxin. Now implicated as a driver of Faecal microbiota transplantation: The introduction of gut inflammation and associated with onset of certain diseases. bacteria from a healthy donor into a patient, through transfer of Metabonome/metabolome an infusion of a faecal sample via nasogastric tube, Aprofile of the chemicals in a tissue or sample, for example the nasoduodenal tube, rectal enema or the biopsy channel of a urine metabonome. This profile represents a snapshot in time of colonoscope.111 what chemicals are present in the sample. Metagenomics A method which allows us to create catalogues of what the that the ratio of the Firmicutes:Bacteroidetes is not the same in bacteria can do based on the genes that they have. all individuals. Currently we do not know the significance of Microbiome being at either end of this continuum, especially as a large shift A collection of different microbes and their functions or genes in the relative abundance of a group of organisms translates to a found in an environmental habitat. Different parts of the body modest change in bacterial numbers. Yet there is evidence that have different microbiomes, for example, the skin microbiome is depletion of a single species, for example, Faecalibacterium different to the gut microbiome, but they are all part of the prausnitzii, belonging to the Firmicutes phylum, has been asso- human microbiome.