Introduction
Irritable bowel syndrome (IBS) is a common condition reported to affect up to 30% of some populations 1. It is a chronic functional and sometimes debilitating disorder of the gastrointestinal tract that can impact quality of life.
IBS has no known cause, however there is an association between the development of IBS symptoms and gastrointestinal inflammation, inflammatory bowel disease, following acute bacterial or viral gastroenteritis, genetic factors, and small intestinal bacterial overgrowth (SIBO). Diagnosis is made in a clinical setting and the criteria for IBS include abdominal pain or discomfort, and an alteration in bowel habit 2.
Studies have reported a strong association between SIBO and IBS. In some cases, the incidence of SIBO in those diagnosed with IBS is 78% 1. In most studies, the presence of SIBO was higher in IBS patients when compared to controls, concluding that SIBO is associated with IBS 1.
Symptoms of IBS are very similar to those experienced by SIBO and can consist of abdominal pain or discomfort, bloating, diarrhoea and/or constipation, and quite commonly fatigue 3. A number of conditions are reported to occur more often in those with IBS and include oesophageal reflux, fibromyalgia, headaches, backaches, and psychological symptoms 3.
IBS is classified into four categories; IBS-D (IBS with diarrhoea), IBS-C (IBS with constipation), IBS-M (mixed diarrhoea and constipation), IBS-A (Alternating diarrhoea and constipation) 4.
Small Intestinal Bacterial Overgrowth
Small intestinal bacterial overgrowth (SIBO) occurs when there is an excessive amount of bacteria in the small intestine. Bacteria are normally present throughout the gastrointestinal tract with the highest concentrations in the colon. When there is too much bacteria in the small intestine, the bacteria interfere with the normal digestion and absorption process within the small intestine and impair intestinal function.
SIBO is usually defined as the presence of >105 colony forming units (CFU)/mL of bacteria in the small intestine. It has been suggested however, that a lower colony count (e.g. >103 cfu/mL) may be enough to cause symptoms in an individual 6. An excessive amount of bacteria in the small intestine disrupts the normal function of the gut. The bacteria ferment food entering the small intestine from the stomach and produce gases such as hydrogen, methane and carbon dioxide. Hydrogen and methane diffuse out into the blood stream and travel in the blood to the lungs. Exhaled concentrations of hydrogen and methane are measured by having a Hydrogen & Methane breath test performed.
When SIBO is present, it may significantly affect the absorption of nutrients and damage the lining of the small intestine which may lead to leaky gut. Leaky gut is associated with immune reactions, autoimmune diseases, and generalised inflammation. There is a strong association between SIBO and Irritable bowel syndrome, Fibromyalgia, Acne Rosacea, Celiac Disease, Crohn’s Disease, Diabetes. Other factors and conditions associated with SIBO include; low stomach acid, reduced intestinal motility, reduced bile and immunoglobulin secretions, weak valve that separates small and large intestine, gastric/intestinal surgery, bowel strictures, diverticuli/outpouchings of the small intestine, certain neurological and muscular diseases, cirrhosis of the liver, alcohol abuse, scleroderma, restless leg syndrome, chemotherapy and pelvic radiotherapy.
The Hydrogen and Methane Breath Test is non-invasive and can be carried out at either one of our clinics, or it can be performed at home using our breath testing kits. Testing and analysis is performed by a fully accredited GI Physiologist.
Causes, benefits, and consequences of SIBO and Gut bacteria
In healthy individuals, it is normal for small numbers of bacteria to be present in the stomach and small intestine. In the distal part of the small intestine, the bacteria more commonly resemble that of the colon. These are mostly gram negative aerobes but with a minor contribution from anaerobes present. This region is separated by the ileo-cecal valve, which acts like a barrier. At the ileocecal valve, the intestinal transit of luminal contents is slowed, allowing some colonic bacteria to move into the terminal ileum 7. Distal to this valve, the bacteria increase in number and consist mainly of anaerobes 8. Bacteria that reside in the proximal colon grow at a fast rate because they have a plentiful supply of dietary nutrients. This results in a decrease in pH because of the vast short chain fatty acid production. In the distal colon, bacteria are more slow growing as substrate availability is lower and the pH is more neutral 9.
It must be considered that the total growth rate may consist of an overgrowth of gram positive bacteria. This is mainly due to upper respiratory flora and this is a common finding in the small intestine of healthy elderly people. It is thought that this type of gram positive bacteria is not associated with symptoms of SIBO. In contrast, the gram negative, anaerobes and enterocci bacteria correlate with such symptoms. They also deconjugate bile acids, affect the binding capacity of intrinsic factor, and reduce the absorptive function of enterocytes 8. It is thought that each individual person has their own distinctive composition of colonic bacteria which appears to be affected by dietary patterns, intake of various nutrients and geographical region. However, it is also suggested that even in those patients with the same diet, the effects of ingested food on individual microflora composition may be very different 10.
There are numerous factors and ‘defence’ mechanisms involved to prevent SIBO, and control the bacterial population in the small intestine. The two major features include; gastric acid secretion which inactivates and destroys many organisms before they enter the proximal segment of the small intestine and, normal intestinal motility (especially Migrating Motor Complexes) which prevents stagnant activity to prohibit the attachment of ingested organisms within the intestinal lumen. Other factors include; immunoglobulins which provides adequate mucosal immunity, the ileocecal valve, and the secretion of digestive enzymes by the pancreatic and billiary systems 6,11.
Migrating Motor Complexes (MMC’S) usually occur between meals, i.e. they are interdigestive. For obvious reasons, MMC’s more often occur at night. They result from migrating electrical complexes which cause regular pressure changes within the wall of the stomach and small intestine. The Myenteric plexus generate the MMC’s, however many hormones including motilin also play an important role in MMC initiation and propagation. MMC’s are replaced by peristalsis and segmenting waves during a meal but may persist if a meal is light. They can start anywhere in the small intestine and travel distally down the GI tract. Their role is important in preventing SIBO by mechanically moving debris and bacteria distally, and lubricating the stomach and small intestine. This is particular to phase III of the MMC cycle which comprises of an uninterrupted band of regular contractions which occurs in the small intestine at a rate of 10-12 min. These are forceful contractions which move the intestinal contents distally. This phase lasts between 2-12 minutes and occurs every 90-120 minutes between meals 12.
A very early study by Vantrappen et al, suggested that disorders of the interdigestive motor complex may be an important factor in the pathogenesis of bacterial colonisation in the small intestine 13. Another study by Stotzeer and associates, demonstrated that patients with SIBO lack interdigestive phase III activity in the small intestine and gastric antrum but have a higher motility index in the distal part of the duodenum. This may be a compensatory increase in motility in the distal intestine 14. Motility dysfunction post GI surgery is a common complication due to autonomic nervous dysfunction and GI hormone disruptions leading to a disruption in the MMC activity 15.
Conditions related to the development of SIBO include:
Stasis (Anatomic):
• Small Bowel Diverticula
• Surgical e.g. resections, ileal bypass, surgically created blind loops
• Intestinal strictures
• Crohn’s disease
• Radiation
• Fistulae 16, 17
Functional Factors
• Intestinal dysmotility syndromes e.g. MMC dysfunction
• Achlorhydria
• Autonomic neuropathy
• Reduction of gut associated lymphoid tissue 6
Miscellaneous
• Cirrhosis
• Acid supressing medications, e.g. proton pump inihibitors, H2 receptor antagonists
• Pancreatitis
• Immune deficiency
• Antimotility medications
• Radiation enteritis
• Diabetes mellitus
• Short bowel syndrome
• Advanced age 6, 16
Abnormal laboratory findings are usually only seen in patients with complex or severe SIBO. There may also be evidence of macrocytic anaemia due to malabsorption of vitamin B12 and the presence of faecal fat. These laboratory findings may include a decrease in thiamine and nicotinamide levels as well as an increase in serum folate and vitamin K levels 17. These findings are not diagnostic features of SIBO but are supportive of the diagnosis. Similarly, endoscopic findings are usually normal in patients with SIBO, however in severe cases where colitis and ileitis occurs; inflammation may be seen during endoscopic examination 17.
Post-surgery, the presence of adhesions may play a role in intestinal stasis and contribute to SIBO. A study by Petrone P. et al showed that in a group of 57 patients who were tested for SIBO, 45 patients had a positive result. Of these 45 patients, 82% had a history of abdominal surgery 18. Small intestinal bacterial overgrowth following a gastrectomy is quite common because of complex reconstructions and pouches. One of the reported reasons is due to the loss of gastric acid, while another reason is the formation of blind-loops 19. Impaired intestinal motility, and disrupted immunologic secretions are also thought to contribute to the development of SIBO in this patient group. Steatorrhoea and megablastic anaemia are the most common clinical features. It is estimated that dumping syndrome can occur in 15-50% of patients following oesophageal and gastric surgery. Paik et al examined a total of 77 patients for bacterial overgrowth post-gastrectomy using a hydrogen-methane glucose breath test and they also performed simultaneous dumping syndrome questionnaires, serum glucose, hematocrit and pulse rate measurements. The prevalence of dumping syndrome in this study was 46.1%. Of those patients tested, 77.6% were found to be positive for SIBO 20.
Benefits of colonic bacteria
Intestinal microflora provides an important role in metabolic and protective functions for the host. In terms of protective function, for example, the microbes assist in preventing pathogens potentially invading the intestinal mucosa by inhibiting attachment and subsequent entry of such pathogens into epithelial cells. Normal flora balance discourages infection by exogenous pathogens and overgrowth of pathogenic organisms by the production of antimicrobial substances or short chain fatty acids, which inhibits the growth of these pathogens 21. Important metabolic functions include the fermentation of nondigestible carbohydrates such as starches, cellulose and pectins (large polysaccharides) and some oligosaccharides that avoided digestion, all of which provide energy to the colon 22.
Colonic microbiotas perform numerous functions that benefit the digestive process. These functions include; the production of micronutrients, the metabolism and/or activation of medications, and the biotransformation of bile salts. Intestinal bacteria play a role in the enterohepatic circulation by producing enzymes which deconjugate bile acids in the colon allowing some reabsorption of bile across the intestinal wall 21. Most however are eliminated in the faeces. Evidence suggests that fibre degradation occurs in the colon. As there are no fibre enzymes, fibre enters the caecum in its unchanged state. The colonic bacteria ferment the fibre to short chain fatty acids, the most important of these are acetate, propionate and butyrate. The major source of energy for colonic epithelium (colonocyte) comes from butyrate 23.
Bifidobacteria (major group of saccharolytic bacteria), makes up approximately 25% of the total bacterial population. It has many health benefits including, lowering blood cholesterol levels, reducing blood ammonia levels, producing vitamins such as B vitamins, folic acid and digestive enzymes such as casein, and lysozyme. It inhibits the growth of potential pathogens and promotes immune function against malignant cells 9. Microflora in the colon also aids in the excretion process of various toxic substances and the flora has also been shown to stimulate immune function through Peyer’s patches and gut-associated lymphoid tissue. Disturbances in immune function can be associated with intestinal diseases such as Ulcerative colitis and Crohn’s disease 10.
Consequences of Small Intestinal Bacterial Overgrowth
One of the major effects of SIBO is the undesirable inflammatory epithelial changes that may result in the dampening of villi, damage to the brush border and leaky gut, and the altered cytokines/mediators which affects the absorption process 6. Normally, in the colon, the epithelial cells and microflora form a barrier that protects the intestine from pathogen invasion. Impairment of this barrier may result in inflammatory disease 22.
Malabsorption of fats is another consequence of SIBO, this occurs because of bile acid deconjugation by intraluminal bacteria which – in turn, affects micelle formation. A significant concentration of conjugated bile acid is required for the formation of these micelles which transport the fat molecules across the intestinal lumen. Therefore, SIBO indirectly damages the absorptive mucosa and can lead to chronic diarrhoea which is secondary to poor fat digestion and absorption 16. Protein and carbohydrate malabsorption as well as fat malabsorption may also be impaired as a result of bile acid deconjugation. This is as a result of substances such as lithocholic acid being produced which exerts a toxic effect on the intestinal epithelium 6.
Anaerobic bacterial utilisation of Vitamin B12 within the intestinal lumen may result in a deficiency in this vitamin and lead to megaloblastic anaemia. Subsequently the bacterial synthesis may lead to an elevation in folate levels 6. Other vitamin deficiencies may also arise as a consequence of SIBO and impaired micelle formation and includes deficiencies in fat-soluble vitamins such as vitamin A (e.g. night blindness), D (osteomalacia, tetany), E and K (prolonged prothrombin times) this however is a rare occurrence 24. Malabsorption of fat and poor fat digestion can lead to steatorrhoea. Diarrhoea can also result from the short-chain fatty acid by-products. This is because they exert an osmotic effect and absorb water into the intestinal lumen 25. Some patients with SIBO however may be asymptomatic 26.
Most importantly, SIBO can very often affect the patient symptomatically. This can be both quite uncomfortable for the patient and can affect their lifestyle and/or quality of life. Symptoms are produced as a result of by-products released by the bacteria when they compete with the natural digestive process and metabolise, particularly carbohydrates, within the lumen of the small intestine. Gases such as Hydrogen, Methane and Carbon Dioxide and short-chain fatty acids are produced. These gases can move in both an antegrade and retrograde direction through the GI tract and cause non-specific GI symptoms such as nausea, abdominal/epigastric discomfort, flatulence and abdominal distension. A large amount of CO2 remains in the small intestine and leads to bloating. These symptoms can often mimic Irritable Bowel Syndrome (IBS). Methane production (measured simultaneously with hydrogen gas production during the SIBO test) slows down gut transit and may cause constipation. In contrast, it has been shown that excess hydrogen production is linked to chronic non-specific diarrhoea and higher stool frequency 27.
Association between SIBO and IBS
Studies have reported a strong association between SIBO and IBS. In some cases, the incidence of SIBO in those diagnosed with IBS is 78% 1. In most studies, the presence of SIBO was higher in IBS patients when compared to controls, concluding that SIBO is associated with IBS 1.
Bloating is a symptom frequently reported in IBS studies, this may be attributed to the excessive amount of gas in the GI tract. Distension of the gut caused by gas can trigger an increased visceral perception. Similarly, those with SIBO often report symptoms of bloating as a result of gas production from bacterial metabolism 1.
In conclusion, studies indicate a high prevalence of SIBO in patients with IBS and those patients tend to have symptom improvement following treatment with antibiotic therapy 5.
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