Primer on Small Intestinal Bacterial Overgrowth
Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or Small bowel
bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small
intestine. Unlike the colon (or large bowel), which is rich with bacteria, the small bowel usually has
fewer than 104 organisms per milliliter.[1] Patients with bacterial overgrowth typically develop symptoms
including nausea, bloating, flatulence, vomiting, diarrhea, malnutrition, weight loss and malabsorption[2]
which is caused by a number of mechanisms.
The diagnosis of bacterial overgrowth is made by a number of techniques, with the gold standard
diagnosis being an aspirate from the jejunum that grows in excess of 105 bacteria per milliliter. Risk
factors for the development of bacterial overgrowth include dysmotility, anatomical disturbances in the
bowel, including fistulae, diverticula and blind loops created after surgery, and resection of the ileocecal valve, gastroenteritis induced alterations to the small intestine as well as the use of certain
medications, including proton pump inhibitors. Small bowel bacterial overgrowth syndrome is treated
with an elemental diet or else antibiotics, which may be given in a cyclic fashion to prevent tolerance to
the antibiotics sometimes followed by prokinetic drugs to prevent recurrence if dysmotility is a
suspected cause.
Symptoms
Deficiency of vitamin B12 can occur in bacterial overgrowth
Bacterial overgrowth can cause a variety of symptoms, many of which are also found in other
conditions, making the diagnosis challenging at times.[1][3] Many of the symptoms are due to
malabsorption of nutrients due to the effects of bacteria which either metabolize nutrients or cause
inflammation of the small bowel impairing absorption. The symptoms of bacterial overgrowth include
nausea, flatus,[4] constipation,[5] bloating, abdominal distension, abdominal pain or discomfort, diarrhea,
fatigue, and weakness.[6] SIBO also causes an increased permeability of the small intestine.[7] Some
patients may lose weight. Children with bacterial overgrowth may develop malnutrition and have
difficulty attaining proper growth. Steatorrhea, a sticky type of diarrhea where lipids are malabsorbed
and spill into the stool, may also occur.[4]
Patients with bacterial overgrowth that is longstanding can develop complications of their illness as a
result of malabsorption of nutrients. Anemia may occur from a variety of mechanisms, as many of the
nutrients involved in production of red blood cells are absorbed in the affected small bowel. Iron is
absorbed in the more proximal parts of the small bowel, the duodenum and jejunum, and patients with
malabsorption of iron can develop a microcytic anemia, with small red blood cells. Vitamin B12 is
absorbed in the last part of the small bowel, the ileum, and patients who malabsorb vitamin B12 can
develop a megaloblastic anemia with large red blood cells.[4] In older adults, small bowel bacterial
overgrowth is associated with a higher frequency of diarrhea, a lower body mass index, and a
significantly lower serum albumin concentration.[8]
Pathophysiology
E. coli, shown in this electron micrograph, is commonly isolated in patients with bacterial
overgrowth
Certain species of bacteria are more commonly found in aspirates of the jejunum taken from patients
with bacterial overgrowth. The most common isolates are Escherichia coli, Streptococcus, Lactobacillus,
Bacteroides, and Enterococcus species.[9]
Soon after birth, the gastrointestinal tract is colonized with bacteria, which, on the basis of models with
animals raised in a germ-free environment, have beneficial effects on function of the gastrointestinal
tract. There are 500-1000 different species of bacteria that reside in the bowel.[10] However, if the flora
of the small bowel is altered, inflammation or altered digestion can occur, leading to symptoms. Many
patients with chronic diarrhea have bacterial overgrowth as a cause or a contributor to their
symptoms.[3]
While the consensus definition of chronic diarrhea varies, in general it is considered to be an alteration
in stool consistency or increased frequency, that occurs for over three weeks. Various mechanisms are
involved in the development of diarrhea in bacterial overgrowth. First, the excessive bacterial
concentrations can cause direct inflammation of the small bowel cells, leading to an inflammatory
diarrhea. The malabsorption of lipids, proteins and carbohydrates may cause poorly digestible products
to enter into the colon. This can cause diarrhea by the osmotic drive of these molecules, but can also
stimulate the secretory mechanisms of colonic cells, leading to a secretory diarrhea.[4]
There is an overlap in findings between tropical sprue, post-infectious irritable bowel syndrome and
small intestinal bacterial overgrowth in the pathophysiology of the three conditions and also SIBO can
similarly sometimes be triggered by an acute gastrointestinal infection.[11][12]
Risk Factors & Causes
The ileocecal valve prevents reflux of bacteria from the
colon into the small bowel. Resection of the valve can lead
to bacterial overgrowth
Certain patients are more predisposed to the development of
bacterial overgrowth because of certain risk factors. These
factors can be grouped into three categories: (1) disordered
motility or movement of the small bowel or anatomical changes
that lead to stasis, (2) disorders in the immune system and (3)
conditions that cause more bacteria from the colon to enter the
small bowel.[1]
Problems with motility may either be diffuse, or localized to particular areas. Diseases like
scleroderma[13] and possibly celiac disease[14] cause diffuse slowing of the bowel, leading to increased
bacterial concentrations. More commonly, the small bowel may have anatomical problems, such as outpouchings known as diverticula that can cause bacteria to accumulate.[15] After surgery involving the
stomach and duodenum (most commonly with Billroth II antrectomy), a blind loop may be formed,
leading to stasis of flow of intestinal contents. This can cause overgrowth, and is termed blind loop
syndrome.[16]
Disorders of the immune system can cause bacterial overgrowth. Chronic pancreatitis, or inflammation
of the pancreas can cause bacterial overgrowth through mechanisms linked to this.[17] The use of
immunosuppressant medications to treat other conditions can cause this, as evidenced from animal
models.[18] Other causes include inherited immunodeficiency conditions, such as combined variable
immunodeficiency, IgA deficiency, and hypogammaglobulinemia.[19]
Finally, abnormal connections between the bacteria-rich colon and the small bowel can increase the
bacterial load in the small bowel. Patients with Crohn's disease or other diseases of the ileum may
require surgery that removes the ileocecal valve connecting the small and large bowel; this leads to an
increased reflux of bacteria into the small bowel.[20] After bariatric surgery for obesity, connections
between the stomach and the ileum can be formed, which may increase bacterial load in the small
bowel.[21]
Proton pump inhibitors, a class of medication that are used to reduce stomach acid, is associated with
an increased risk of developing SIBO.[22]
In recent years, several proposed links between SIBO and other disorders have been made. However,
the usual methodology of these studies involves the use of breath testing as an indirect investigation for
SIBO. Breath testing has been critizised by some authors for being an imperfect test for SIBO, with
multiple known false positives.[23]
Proposed link with Irritable bowel syndrome
Some studies reported up to 80% of patients with irritable bowel syndrome (IBS) have SIBO (using the
hydrogen breath test). Subsequent studies demonstrated statistically significant reduction in IBS
symptoms following therapy for SIBO.[24][25][26]
There is a lack of consensus however, regarding the suggested link between IBS and SIBO. Other authors
concluded that the abnormal breath results so common in IBS patients do not suggest SIBO, and state
that "abnormal fermentation timing and dynamics of the breath test findings support a role for
abnormal intestinal bacterial distribution in IBS." [27] There is general consensus that breath tests are
abnormal in IBS, however the disagreement lies in whether this is representative of SIBO.[28] More
research is needed to clarifiy this possible link.
Proposed link with Fibromyalgia
Fybromyalgia is a poorly understood pain condition. Lactulose breath testing has shown that patients
with fibromyalgia have a more pronounced degree of abnormal results compared to both IBS patients
and the general population.[29] This study also demonstrated positive correlation between the amount of
pain and the degree of abnormality on the breath test. A subsequent study also demonstrated increased
prevalence of intestinal hyperpermeability, which some believe occurs commonly with SIBO.[30]
Proposed link with Rosacea
Intestinal bacteria may play an etiological role in the dermatological condition Rosacea. A recent study
subjected patients to a hydrogen breath test to detect the occurrence of SIBO. It was found that
significantly more patients were hydrogen-positive than controls indicating the presence of bacterial
overgrowth (47% v. 5%, p<0.001).
Hydrogen-positive patients were then given a 10-day course of rifaximin, a non-absorbable antibiotic
that does not leave the digestive tract and therefore does not enter the circulation or reach the skin.
96% of patients experienced a complete remission of rosacea symptoms that lasted beyond 9 months.
These patients were also negative when retested for bacterial overgrowth. In the 4% of patients that
experienced relapse, it was found that bacterial overgrowth had returned. These patients were given a
second course of rifaximin which again cleared rosacea symptoms and normalized hydrogen
excretion.[31]
In another study, it was found that some rosacea patients that tested hydrogen-negative were still
positive for bacterial overgrowth when using a methane breath test instead. These patients showed
little improvement with rifaximin, as found in the previous study, but experienced clearance of rosacea
symptoms and normalization of methane excretion following administration of the antibiotic
metronidazole, which is effective at targeting methanogenic intestinal bacteria.[32]
These results suggest that optimal antibiotic therapy may vary between patients and that diverse
species of intestinal bacteria appear to be capable of mediating rosacea symptoms.
This may also explain the improvement in symptoms experienced by some patients when given a
reduced carbohydrate diet.[33] Such a diet would restrict the available material necessary for bacterial
fermentation and thereby reduce intestinal bacterial populations.
Diagnosis
Aspiration of from the jejunum is the gold standard for diagnosis.
A bacterial load of greater than 105 bacteria per milillitre is
diagnostic for bacterial overgrowth.
The diagnosis of bacterial overgrowth can be made by physicians
in various ways. The gold standard for detection of bacterial
overgrowth is the aspiration of more than 105 bacteria per
millilitre from the small bowel. The normal small bowel has less
4
[35]
than 10 bacteria per millilitre. Some experts however, consider aspiration of more than 103 positive if
the flora is predominately colonic type bacteria as these types of bacteria are considered pathological in
excessive numbers in the small intestine. The reliability of aspiration in the diagnosis of SIBO has been
questioned as SIBO can be patchy and the reproducibility can be as low as 38 percent. Some doctors
factor in a patients' response to treatment as part of the diagnosis.[1]
Biopsies of the small bowel in bacterial overgrowth can mimic
celiac disease, with partial villous atrophy.
Breath tests have been developed to test for bacterial
overgrowth, based on bacterial metabolism of carbohydrates to
hydrogen and/or methane, or based on the detection of byproducts of digestion of carbohydrates that are not usually
metabolized. The hydrogen breath test involves having the
patient fast for a minimum of 12 hours then having them drink a
substrate of glucose, then measuring expired hydrogen and
methane concentrations typically over a period of 2–3 hours. It compares well to jejunal aspirates in
making the diagnosis of bacterial overgrowth.[36] 13C and 14C based tests have also been developed based
on the bacterial metabolism of D-xylose. Increased bacterial concentrations are also involved in the
deconjugation of bile acids. The glycocholic acid breath test involves the administration of the bile acid
14
C glychocholic acid, and the detection of 14CO2, which would be elevated in bacterial overgrowth.[37]
Some patients with symptoms of bacterial overgrowth will undergo gastroscopy, or visualization of the
stomach and duodenum with an endoscopic camera. Biopsies of the small bowel in bacterial overgrowth
can mimic those of celiac disease, making the diagnosis more challenging. Findings include blunting of
villi, hyperplasia of crypts and an increased number of lymphocytes in the lamina propria.[38]
However, some physicians suggest that if the suspicion of bacterial overgrowth is high enough, the best
diagnostic test is a trial of treatment. If the symptoms improve, an empiric diagnosis of bacterial
overgrowth can be made.[39]
Treatment
Bacterial overgrowth is usually treated with a course of antibiotics although whether antibiotics should
be a first line treatment is a matter of debate. Some experts recommend probiotics as first line therapy
with antibiotics being reserved as a second line treatment for more severe cases of SIBO. Prokinetic
drugs are other options but research in humans is limited.[40][41] A variety of antibiotics, including
tetracycline, amoxicillin-clavulanate, fluoroquinolones, metronidazole, neomycin, cephalexin,
trimethoprim-sulfamethoxazole have been used; however, the best evidence is for the use of
rifaximin.[42]
A course of one week of antibiotics is usually sufficient to treat the condition. However, if the condition
recurs, antibiotics can be given in a cyclical fashion in order to prevent tolerance. For example,
antibiotics may be given for a week, followed by three weeks off antibiotics, followed by another week
of treatment. Alternatively, the choice of antibiotic used can be cycled.[39]
The condition that predisposed the patient to bacterial overgrowth should also be treated. For example,
if the bacterial overgrowth is caused by chronic pancreatitis, the patient should be treated with coated
pancreatic enzyme supplements.
Probiotics are bacterial preparations that alter the bacterial flora in the bowel to cause a beneficial
effect. Animal research has demonstrated that probiotics have barrier enhancing, antibacterial, immune
modulating and anti-inflammatory effects which mmay have a positive effect in the management of
SIBO in humans.[1] Lactobacillus casei has been found to be effective in improving breath hydrogen
scores after 6 weeks of treatment presumably by suppressing levels of a small intestinal bacterial
overgrowth of fermenting bacteria.[43] The multi-strain preparation VSL#3 was found to be effective in
suppressing SIBO.[44] Lactobacillus plantarum, lactobacillus acidophilus, lactobacillus casei have all
demonstrated effectiveness in the treatment and management of SIBO. Conversely lactobacillus
fermentum and saccharomyces boulardii have been found to be ineffective.[1] A combination of
lactobacillus plantarum and lactobacillus rhamnosus has been found to be effective in suppressing
bacterial overgrowth of abnormal gas producing organisms in the small intestine.[45] Probiotics are
superior to antibiotics in the treatment of SIBO.[7] A combination of probiotic strains has been found to
produce better results than therapy with the antibiotic drug metronidazole.[46][47] Probiotics taken in
uncomplicated cases of SIBO can usually result in the individual becoming symptom free.[48] Probiotic
therapy may need to be continuously to prevent the return of overgrowth of gas producing bacteria.[49]
Probiotic yogurt may also be effective in treating SIBO with evidence of reduced inflammation after 4
weeks of treatment.[50]
An elemental diet taken for two weeks is an alternative to antibiotics for eliminating SIBO. An elemental
diet works via providing nutrition for the individual while depriving the bacteria of a food source.[51]
Additional treatment options include the use of prokinetic drugs such as 5-HT4 receptor agonists or
motilin agonists to extend the SIBO free period after treatment with an elemental diet or antibiotics.[52]
A diet void of certain foods that feed the bacteria can help alleviate the symptoms.[43] For example if the
symptoms are caused by bacterial overgrowth feeding on indigestible carbohydrate rich foods, following
a FODMAP restriction diet may help.[53]
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