Table of Contents  

Quigley: The microbiome revolution – how can we translate the science into clinical practice?

The gut microbiome – the basics

If the microbiome revolution is truly upon us, we can attribute much of this progress to the rapid evolution of the technologies that allow us to document in detail the components of the microbiome (through high-throughput sequencing) and their genetic make-up (through metagenomics) and metabolic potential (through metabolomics).1,2 These techniques have identified symbiotic relationships between our bacterial fellow-travellers and our immune, metabolic and neuroendocrine systems, and the consequences of a breakdown in this mutual interdependence in terms of disease causation is being increasingly revealed.

With every new field of biological endeavour comes a new vocabulary that, as in many other instances, can be confusing and even confused. Thus, although the term ‘microbiota’ should refer to the totality of micro-organisms in a given environment and ‘microbiome’ to the entire habitat (i.e. the totality of micro-organisms in a given environment together with their collective genetic material and the surrounding environmental conditions), these terms are often used interchangeably, even by experts. The term ‘metagenome’ refers to the collection of genomes and genes from the members of a microbiota and the metabolome to its metabolic products.

The gut microbiota in health

The gut microbiota will inevitably be influenced by the microenvironment in which it lives, the hypoxic climate of the colon favouring the domination of strict anaerobes and facultative anaerobes. Not surprisingly, the diet of the host is being increasingly recognized, in both the short and the long term, as a powerful modulator of microbiota composition and function.3 Antibiotic exposure, whether in typical therapeutic doses or in much smaller amounts, such as those that reach us through the food chain, may have impacts that persist well beyond the actual duration of exposure.4 Bacteria–host interactions are bidirectional and host genetics and, as well as the presence of inflammation or disease, are now recognized to influence the gut microbiota – observations that complicate the interpretation of microbial signals in disease states.5 Although variability in microbiota composition between individuals is the order of the day, we do share a common (‘core’) gut microbiome6 and further groupings, probably driven by dietary preferences, are evident at higher levels of organization.3

At birth, the human gut is relatively sterile and acquires its microbial population during birth and based on its environmental exposures over the first few months of life.7,8 Thereafter, the gut microbiota rapidly evolves in terms of both bacterial numbers and diversity, and achieves its ‘adult’ composition at about the age of 2 years.7 Unless disrupted by external influences or host disease, the microbiota remains relatively stable until old age, when changes, driven in part by diet and the inflammatory state that occurs in later life (‘inflammaging’), take place.9 Given how rapidly the microbiota of each individual develops through early childhood, it is likely that this same period is highly sensitive to disruption, impacts that could well lay the basis for the appearance of diseases, such as obesity and inflammatory bowel disease, much later in life. At a very basic level it is now evident that the composition of the infant’s microbiota is directly affected by mode of delivery (vaginal birth vs. caesarean section), diet (breast milk vs. formula), level of sanitation, exposure to vaccinations and other contacts.8

Recent decades have witnessed not just an appreciation of the fundamental and enduring contributions of the microbiome to the development of the gastrointestinal tract, in the first instance, but also to the maintenance of gastrointestinal health thereafter.10,11 Key homeostatic gut functions such as immunological tolerance, the development of the mucosal, or gut-associated, immune system, epithelial and gut barrier integrity, as well as motility and vascularity are profoundly influenced by interactions with the microbiota.10,11 The influence of the gut microbiome extends well beyond the gut wall, as evidenced by the emergence of such concepts as the microbiota–gut–liver axis12,13 and the microbiota–gut–brain axis.14

The metabolic functions of the microbiota have engendered a major focus on the potential role of an altered or ‘dysfunctional’ microbiota in obesity and the metabolic syndrome, especially as they relate to the salvage of calories from dietary components inaccessible to the human enzymatic repertoire. The contributions of the microbiota to drug metabolism were recognized many decades ago through pioneering work on sulphasalazine;15 it is now evident that several commonly used drugs may also be subject to bacterial enzymatic modulation.16

The microbiome in disease

Some of the disorders related to a disturbed microbiome, such as antibiotic-associated diarrhoea, necrotizing enterocolitis and hepatic encephalopathy, have been recognized for some time and the role of microbe–host interactions in their pathogenesis well delineated.17,18 Not a day goes by but some disease or disorder is linked to an ‘abnormal’ microbiota. Many of these linkages are, at best, speculative; in others, available data describe association and at this time no conclusions can be drawn with respect to causation.1822

References

1. 

Fraher MH, O’Toole PW, Quigley EMM. Techniques used to characterise the intestinal microbiota: a guide for the clinician. Nat Rev Gastroenterol 2012; 9:312–22. http://dx.doi.org/10.1038/nrgastro.2012.44

2. 

Lepage P, Leclerc MC, Joossens M, et al. A metagenomic insight into our gut’s microbiome. Gut 2013; 62:146–58. http://dx.doi.org/10.1136/gutjnl-2011-301805

3. 

Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature 2011; 473:174–80. http://dx.doi.org/10.1038/nature09944

4. 

Blaser MJ. Antibiotic use and its consequences for the normal microbiome. Science 2016; 352:544–5. http://dx.doi.org/10.1126/science.aad9358

5. 

Quigley EM. Gut bacteria in health and disease. Gastroenterol Hepatol 2013; 9:560–9.

6. 

Karlsson FH, Nookaew I, Nielsen J. Metagenomic data utilization and analysis (MEDUSA) and construction of a global gut microbial gene catalogue. PLoS Comput Biol 2014; 10:e1003706. http://dx.doi.org/10.1371/journal.pcbi.1003706

7. 

Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature 2012; 486:222–7. http://dx.doi.org/10.1038/nature11053

8. 

Fouhy F, Ross RP, Fitzgerald GF, et al. Composition of the early intestinal microbiota – knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes 2012; 4:1–18.

9. 

Claesson MJ, Jeffery IB, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 2012; 488:178–84.

10. 

Sekirov I, Russell SL, Antunes LC, et al. Gut microbiota in health and disease. Physiol Rev 2010; 90:859–904. http://dx.doi.org/10.1152/physrev.00045.2009

11. 

Elson CO, Alexander KL. Host–microbiota interactions in the intestine. Dig Dis 2015; 33:131–6. http://dx.doi.org/10.1159/000369534

12. 

Quigley EM, Stanton C, Murphy EF. The gut microbiota and the liver. Pathophysiological and clinical implications. J Hepatol 2013; 58:1020–7. http://dx.doi.org/10.1016/j.jhep.2012.11.023

13. 

Victor DW 3rd, Quigley EM. Microbial therapy in liver disease: probiotics probe the microbiome–gut–liver–brain axis. Gastroenterology 2014; 147:1216–18. http://dx.doi.org/10.1053/j.gastro.2014.10.023

14. 

Cryan JF, O’Mahony SM. The microbiome–gut–brain axis: from bowel to behaviour. Neurogastroenterol Motil 2011; 23:187–92. http://dx.doi.org/10.1111/j.1365-2982.2010.01664.x

15. 

Azad Khan AK, Truelove SC, Aronson JK. The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man. Br J Clin Pharmacol 1982; 13:523–8. http://dx.doi.org/10.1111/j.1365-2125.1982.tb01415.x

16. 

Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013; 342:971–6. http://dx.doi.org/10.1126/science.1240537

17. 

Martin JS, Monaghan TM, Wilcox MH. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission. Nat Rev Gastroenterol Hepatol 2016; 13:206–16. http://dx.doi.org/10.1038/nrgastro.2016.25

18. 

Quigley EM, Monsour HP. The gut microbiota and the liver: implications for clinical practice. Expert Rev Gastroenterol Hepatol 2013; 7:723–32. http://dx.doi.org/10.1586/17474124.2013.848167

19. 

Shanahan F, Quigley EM. Manipulation of the microbiota for treatment of IBS and IBD-challenges and controversies. Gastroenterology 2014; 146:1554–63. http://dx.doi.org/10.1053/j.gastro.2014.01.050

20. 

Quigley EM, Spiller RC. Constipation and the microbiome: lumen versus mucosal. Gastroenterology 2016; 150:300–3. http://dx.doi.org/10.1053/j.gastro.2015.12.023

21. 

Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun 2015; 6:6528. http://dx.doi.org/10.1038/ncomms7528

22. 

Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 2015; 30:350–8. http://dx.doi.org/10.1002/mds.26069




Add comment 





Home  Editorial Board  Search  Current Issue  Archive Issues  Announcements  Aims & Scope  About the Journal  How to Submit  Contact Us
Find out how to become a part of the HMJ  |   CLICK HERE >>
© Copyright 2012 - 2013 HMJ - HAMDAN Medical Journal. All Rights Reserved         Website Developed By Cedar Solutions INDIA