Concept of human bowel flora as a
It is useful to compare the human faecal flora to a living organ because its major component is a complex mass of living cells. Furthermore, it interacts with the human body and the human body interacts with it. Given that the human body is made up of approximately 1014 cells - while 1 x 1013 are body cells, about 9 x 1013 cells are bacteria contained within the bowel. Hence, purely on cell count we are 10% human and 90% stool! 1
The body is large in size because it contains much connective tissue, whereas the human flora exists as a small, tightly packed mass of bacterial cells. If we conceptualise human bowel flora as an organ it helps us understand how it can function as a normal, healthy organ or as an organ that can undergo various illness states. Such a concept is not far removed from the standard medical concepts of healthy or diseased organs such as liver (hepatitis, alcohol-induced disease etc), lung (pneumonia, asthma, emphysema etc), heart (coronary artery disease, rheumatic fever etc). Generally, each organ develops disorders peculiar to the structure and function of that organ.
The human flora is considered to be healthy if clinically the patient is not suffering any disorders that might be related to it and generally has painless, soft daily bowel movements without any bleeding, and a normal amount of flatus. Furthermore, on examination the normal components of the flora should be in their usual, accepted qualitative/quantitative numbers and there should be no detectable pathogens present. With such a working definition we can then move to the description of what constitutes an unhealthy bowel flora.
Each body organ responds to various disease processes in a limited number of ways. The disease process affects the organ in question which in turn may affect surrounding organs and the rest of the body. For example obstruction of small blood vessels in the heart may lead to an arrhythmia and perhaps death. Yet such vessel obstruction in the lung or the brain will not cause arrhythmia but will have a different pathological and clinical effect. Some organs develop inflammatory responses (eg. dermatitis). The bowel flora can also respond in a limited number of ways to disease processes. The bowel flora is incapable of having a blood vessel obstructed or being inflamed - albeit inflammatory cells can be detected in the flora. Most organs can develop neoplastic changes. The bowel flora is not capable of developing a benign or a malignant change in bacterial cells as far as we know. However, the bowel flora is quite capable of becoming infected by a variety of pathogens. Hence, its response is generally limited to the proliferation of pathogenic bacterial (and other) cells, toxin production, production of various bio-active (or pro-inflammatory) molecules, gas production, as well as the suppression of normal bacterial components and even loss of bacterial components. As the result of infection the flora can directly affect its immediate human tissues - the bowel - and at times other parts of the body. The bowel may respond with excessive fluid secretion (cholera), inflammation (colitis), pain or cramping (IBS), trapping gas (bloating), partial paralysis (constipation as in botulism and idiopathic constipation) among other responses. Various combinations of these responses may also co-exist. The infected flora therefore affects primarily the muscular container (bowel) in which the bowel flora resides, but through the production of toxins and pro-inflammatory products and the associated bowel inflammation it is easier to understand how other parts of body may be affected. Having understood how known infective bacteria (e.g. shigella) can bring about inflammation of the mucosal lining resulting in infective colitis, it is easier for us to comprehend how 'idiopathic colitis' could possibly be caused by a chronic faecal infection whose pathogens are still to be discovered. Furthermore, infected bowel flora can transmit infective agents that can then invade the bowel wall e.g. Mycobacterium tuberculosis causing TB of the distal small bowel or the colon. In a similar fashion Mycobacterium avium subspecies paratuberculosis can be transmitted by infected bowel flora to the distal small bowel and colon resulting in Crohn's disease. (see www.crohns.org)
Other parts of the body may suffer from the effects of flora infection because of the severe nature of local colonic changes or absorbed toxins. If there is colonic bleeding, frequency, mucus production, and fluid loss for example, the entire body may be affected by anaemia, tiredness, malaise or dehydration effects. Some infective agents may secrete molecules which when absorbed may result in anorexia, nausea, vomiting as well as profound weakness and even death (botulism), called 'para-infective' phenomena.
Just as other body organs suffer infectious diseases and can be treated with anti-microbial drugs, so infection of the bowel flora is frequently treated for parasites or bacterial infections. In situations of serious diseases of body organs, topping up of a missing organ (eg. blood transfusion or skin graft) is resorted to. At times, transplantation of the entire organ is necessary (e.g. heart, liver or bone marrow transplant). The bowel flora may also be 'topped up' (probiotic use) and at times it can be fully transplanted (Human Probiotic flora Infusion - HPI).
The most common disease state which affects the bowel flora is infection. In this condition, human stool or faecal flora becomes infected with a pathogen or pathogens. Numerous pathogens can infect the human flora. They can be viral, bacterial, fungal or helminthic. Furthermore, such infections can be classified as acute, sub-acute or chronic (persistent). From yet another angle, bowel flora infections can be viewed as being detectable or undetectable. For example, in adults many acute diarrhoeal episodes are clearly infective in nature, yet in most situations we do not detect any pathogens. Many chronic diarrhoeal states carry a similar infective mechanism. It is the 'undetectable' group that holds much promise as an area where research and the elimination of 'not-yet-described' infective agents could bring about much change in the way we view the human flora. Disorders we have not yet considered to be caused by the human flora e.g. IBS, constipation or inflammatory bowel disease (IBD) may indeed be linked to flora imbalances.
There is an ever-expanding list of pathogens that have been thought to cause acute infection of the flora. These generally cause diarrhoea. Nonetheless it has to be remembered that the GI flora can become acutely infected causing no symptoms - simply carrier status, eg. Clostridium difficile or certain worms - and in some situations can cause constipation, flatulence, anorexia and weight loss. Such infections are well known. Examples of acute infections include viral pathogens eg. rotavirus, Norwalk virus, enteric adenovirus, calcivirus, astrovirus; bacterial pathogens eg. salmonella, shigella, campylobacter, enterotoxigenic E. coli, Clostridium perfringens, yersinia, vibrio, bacillus cereus and protozoa e.g. cryptosporidium.
Patients with persistent infection may present to the doctor with many weeks to years of diarrhoea, bloating, flatulence, cramps and incontinence as well as constipation. Apart from local bowel effects of such chronic flora infections, distant symptoms outside the bowel can be caused by pathogens and are called 'para-infective phenomena'. They can include nausea and vomiting, tiredness, joint pains, headaches, malaise, fevers, reflux and pain on swallowing among others. Symptoms may be mild in some patients yet severe in others for various reasons. Multiple infections can co-exist in some patients. Examples of known persistent infections of the flora are listed below. However, it has to be remembered that the overwhelming majority of persistent bowel flora infections, perhaps 80%, are still to be named and diagnosed because science has not yet identified and described all pathogens.
Some examples of persistent bowel flora infections include C. difficile, C. perfringens, Aeromonas sp., Entamoeba histolytica, Dientamoeba fragilis, Giardia lamblia, Yersinia enterocolitica and many other parasites. Candida albicans rarely plays a pathogenic infective role in the bowel except in some situations of severe immunodeficiency e.g. AIDS.
The normal human bowel flora is made up of a large number of different bacterial components including the Bacteroides species, eubacteria, clostridia, bifidobacteria, E. coli and others. Unlike the composition of blood which is well studied and known the composition of the bowel flora has received comparatively little research attention and remains poorly understood. At best no more than 50% of the bacterial components have actually been cultured or named and research is now heading towards DNA characterisation of components to better describe the human flora. It has recently become clear that some species of bacteria can be completely absent in the bowel flora of some individuals. This has been especially documented in those patients who, after antibiotic treatment, had complete absence of Bacteroides species in association with chronic infection with C. difficile.2 Bacteroides and E. coli deficiency has also been observed in patients with irritable bowel syndrome and chronic fatigue syndrome.3 Generally, deficient flora appears to be infected or replaced with other pathogenic bacteria that fill the gap left by the absent normal flora components.