key: cord-272547-ld1bux2h
authors: Eslick, Guy D.
title: Future Perspectives on Infections Associated with Gastrointestinal Tract Diseases
date: 2010-10-09
journal: Infect Dis Clin North Am
DOI: 10.1016/j.idc.2010.08.002
sha: 
doc_id: 272547
cord_uid: ld1bux2h

There are a vast number of infectious agents that are associated with gastrointestinal (GI) tract diseases. The epidemiology of GI diseases is changing, with a greater number of conditions increasing in incidence. Challenges exist with establishing cause-and-effect relationships because of the ubiquitous nature of these organisms and the milieu in which they exist. Advances in technology should provide novel methods for identifying and diagnosing these organisms and the relationship they have with a specific digestive disease.

prevalence were observed for certain GI tract diseases, including gastroesophageal reflux disease (GERD) with an increase of 376 per 100,000 population, hepatitis C with 79 per 100,000 population, chronic constipation with 62 per 100,000 population, intestinal infections with 41 per 100,000 population, and pancreatitis with 23 per 100,000 population. 1 The prevalence of digestive diseases around the world is enormous and varies from country to country ( Table 2) . Worldwide there has been a dynamic shift in the epidemiology of GI tract diseases, with some diseases such as peptic ulcer decreasing dramatically since the discovery of Helicobacter pylori infection and a larger number of conditions increasing, such as GERD, nonalcoholic fatty liver disease, diverticular disease, Barrett esophagus, cholelithiasis, alcoholic liver disease, hepatitis C, chronic pancreatitis, esophageal cancer and colorectal cancer. [3] [4] [5] [6] [7] [8] In conjunction with this increasing incidence of digestive diseases are the re-emergence of certain infectious agents (Box 1) (eg, cholera) and the identification of new agents (eg, H pylori, Laribacter, Campylobacter concisus), which are associated with GI tract diseases. 9 Since the discovery of H pylori there has been an enormous interest in the relationship between microorganisms and GI tract diseases, including cancers.

One of the main issues associated with infections and disease is determining the relationship of the cause and effect. The landmark article by Sir Austin Bradford Hill in 1965 titled The environment and disease: association or causation? became widely known as the Bradford Hill's criteria. 10 There were 8 criteria that were required to be met to determine a cause-and-effect relationship (Box 2). It is usually difficult to meet all these criteria, particularly when trying to find the cause-and-effect relationships between organisms in the small intestine or colon because of the large number of organisms living in these environments. Even for H pylori infection and the relationship with gastric cancer, although it is currently the only bacterium classified as a class I carcinogen, the evidence supporting this relationship is not complete in terms of Bradford Hill's criteria.

There are a large number of organisms believed to be responsible for diseases of the digestive system. Some of these organisms are true pathogens, whereas others are merely commensal in nature and are unlikely to ever produce any pathologic condition. Table 3 shows the various types of microbes that are associated with diseases of the GI tract covered in this issue; it is by no means all-inclusive but provides the current magnitude of an ever-increasing field of research. At present, some of these diseases are only associated with a single group of organisms (eg, irritable bowel syndrome), whereas other diseases are affected by all groups of organisms (eg, appendicitis).

There are a variety of methodological and technical issues related to infectious agents and their role in digestive diseases. For diseases of the colon, the major limitation remains the inability to completely identify these organisms. Identification of bacteria was mainly conducted using culture-based methods. Now, the focus in identification of bacteria is increasingly based on using molecular techniques. Many of these techniques allow the detection and identification of viable but nonculturable cells that are metabolically active but not reproducing. Gene sequencing using single-stranded RNA has been a key method in being able to elucidate multitudes of organisms that remain unknown. At present, there are approximately 9000 bacterial species, and this number is estimated as just the tip of the iceberg. The development of molecular Studies of the emergence and/or spread of antimicrobial resistance genes within pathogen populations methods offers great promise not only in research and development but also in the diagnostic setting (eg, stool samples) ( Table 4) . 11, 12 Clearly, metagenomics, in which genetic material is directly retrieved from environmental sources, will play a critical role in the future development of determining infectious agents of the GI tract. The use of high-throughput technology has already produced important findings in relation to the GI tract microflora, including the differences between adults and children, with numerous uncultured organisms being the crux of the normal human adult gut flora which remain stable but other organisms change depending on environmental and genetic factors, whereas in infants there appear to be a constant transformation of organisms over time (Figs. 3 and 4) . 11 There have been several new detection methods developed, with some of these using nanoscale electrochemical detectors and others using DNA sensors (extrachromosomal DNA). 13 The use of stable-isotope probing is also being investigated, but even this technique has limitations. 14 Although these technologies are increasing the understanding of the gut microflora, there remains large gaps of knowledge regarding the metabolic functions of these organisms and the relationship they have with human GI disease. These will be extremely fruitful areas of research and development in the coming years.

Research on therapeutic approaches that target resistance mechanisms Modification of existing antimicrobials to overcome emergent resistance Antimicrobial research, as related to engineered threats and naturally occurring drugresistant pathogens, focused on the development of broad-spectrum antimicrobials 

The burden of digestive diseases in the United States. US Department of Health and Human Services

Cancer statistics

Changing trends in gastrointestinal disease in the Asia-Pacific region

The burden of gastrointestinal and liver diseases

Burden of digestive diseases in the United States part I: overall and upper gastrointestinal diseases

Burden of digestive diseases in the United States part II: lower gastrointestinal diseases

Burden of digestive diseases in the United States part III: liver, biliary tract, and pancreas

The burden of gastrointestinal disease: implications for the provision of care in the UK

Emerging infections of the gastrointestinal tract

The environment and disease: association or causation?

High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota

Advances in nucleic acid-based diagnostics of bacterial infections

Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection of DNA3

Tools for the tract: understanding the functionality of the gastrointestinal tract