Small bowel bacterial overgrowth syndrome (
SBBOS), or
small intestinal bacterial overgrowth (
SIBO), also termed
bacterial overgrowth; is a disorder of excessive bacterial growth in the
small intestineIn vertebrates, the small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where the vast majority of digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large...
. Unlike the
colonThe colon is the last portion of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body....
(or large bowel), which is rich with
bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, the small bowel usually has less than 10
4 organisms per millilitre. Patients with bacterial overgrowth typically develop symptoms including
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
,
bloatingBloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Causes:Bloating may have...
,
vomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Undesired vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure...
and
diarrheaIn medicine, diarrhea , also spelled diarrhoea , is the condition of having frequent loose or liquid bowel movements. Acute diarrhea is a common cause of death in developing countries and the second most common cause of infant deaths worldwide...
, which is caused by a number of mechanisms. The
diagnosisIn medicine, diagnosis is a label given for a medical condition or disease identified by its signs, symptoms, and from the results of various diagnostic procedures...
of bacterial overgrowth is made by a number of techniques, with the
gold standardIn medicine, gold standard test refers to a diagnostic test or benchmark that is regarded as definitive.This can refer to diagnosing a disease process, or the criteria by which scientific evidence is evaluated...
diagnosis being an
aspirateNeedle aspiration biopsy , also known as fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
from the
jejunumThe jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
that grows in excess of 10
5 bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
per millilitre.
Risk factorA risk factor is a variable associated with an increased risk of disease or infection. Risk factors are correlational and not necessarily causal, because correlation does not imply causation...
s for the development of bacterial overgrowth include the use of medications including proton pump inhibitors,
anatomicalAnatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy and plant anatomy...
disturbances in the bowel, including
fistulaIn medicine, a fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect. It is generally a disease condition, but a fistula may be surgically created for therapeutic reasons.-Location of fistulas:Fistulas can develop in various...
e, diverticula and blind loops created after surgery, and resection of the ileo-cecal valve. Small bowel bacterial overgrowth syndrome is treated with
antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
s, which may be given in a cyclic fashion to prevent tolerance to the antibiotics.
Clinical presentation
Bacterial overgrowth can cause a variety of
symptomA symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s, many of which are also found in other conditions, making the
diagnosisIn medicine, diagnosis is a label given for a medical condition or disease identified by its signs, symptoms, and from the results of various diagnostic procedures...
challenging at times. Many of the symptoms are due to
malabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
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
nauseaNausea is the sensation of unease and discomfort in the stomach with an urge to vomit.-Causes:...
,
bloatingBloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Causes:Bloating may have...
, flatus, and
chronicChronic may refer to:* Chronic , a persistent and lasting disease or medical condition, or one that has developed slowly* Chronic toxicity,* The Chronic, a 1992 album by Dr. Dre...
diarrheaIn medicine, diarrhea , also spelled diarrhoea , is the condition of having frequent loose or liquid bowel movements. Acute diarrhea is a common cause of death in developing countries and the second most common cause of infant deaths worldwide...
. Some patients may develop abdominal discomfort and lose weight. Children with bacterial overgrowth may develop
malnutritionMalnutrition is the insufficient, excessive or imbalanced consumption of nutrients.A number of different nutrition disorders may arise, depending on which nutrients are under or overabundant in the diet....
and have difficulty attaining
proper growthFailure to thrive is a medical term which denotes poor weight gain and physical growth failure over an extended period of time. Common usage refers to infancy. However, the term is also applied to geriatrics. As used by pediatricians, it covers poor physical growth of any cause and does not imply...
.
SteatorrheaSteatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
is a sticky type of diarrhea, where
lipidLipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others...
s are malabsorbed and spill into the stool.
Patients with bacterial overgrowth that is longstanding can develop complications of their illness as a result of malabsorption of nutrients.
AnemiaAnemia is a decrease in normal number of red blood cells or less than the normal quantity of hemoglobin in the blood...
may occur from a variety of mechanisms, as many of the nutrients involved in production of
red blood cellRed blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen to the body tissues via the blood. They take up oxygen in the lungs or gills and release it while squeezing through the body's capillaries. The cells are filled with hemoglobin, a...
s are absorbed in the affected small bowel.
IronIron is a metallic chemical element with the symbol Fe and atomic number 26. Iron is a group 8 and period 4 element and is therefore classified as a transition metal. Iron and iron alloys are by far the most common metals and the most common ferromagnetic materials in everyday use...
is absorbed in the more proximal parts of the small bowel, the
duodenumThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
and
jejunumThe jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
, and patients with malabsorption of iron can develop a
microcytic anemiaMicrocytic anemia is a generic term for any type of anemia characterized by small red blood cells. The normal mean corpuscular volume is 76-100 fl, with smaller cells described as microcytic and larger cells as macrocytic.In microcytic anemia, the red blood cells are usually also...
, with small red blood cells.
Vitamin B12Vitamin B12 is a water soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
is absorbed in the last part of the small bowel, the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
, and patients who malabsorb vitamin B12 can develop a
megaloblastic anemiaMegaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B and/or folic acid...
with large red blood cells.
Pathophysiology
Certain species of bacteria are more commonly found in aspirates of the
jejunumThe jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
taken from patients with bacterial overgrowth. The most common isolates are
Escherichia coliEscherichia coli , is a Gram negative bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E...
,
StreptococcusStreptococcus is a genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the lactic acid bacteria group. Cellular division occurs along a single axis in these bacteria, and thus they grow in chains or pairs, hence the name — from Greek στρεπτος streptos, meaning...
,
LactobacillusLactobacillus is a genus of Gram-positive facultative anaerobic or microaerophilic bacteria. They are a major part of the lactic acid bacteria group, named as such because most of its members convert lactose and other sugars to lactic acid. They are common and usually benign...
,
BacteroidesBacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...
, and
EnterococcusEnterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Members of this genus were classified as Group D Streptococcus until 1984 when genomic DNA analysis indicated that a separate genus classification would be appropriate....
species.
Soon after birth, the
gastrointestinal tractThe human gastrointestinal tract , digestive tract, guts or gut is the system of organs within humans that takes in food, digests it to extract energy and nutrients, and expels the remaining matter...
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. 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. 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
lipidLipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, phospholipids, and others...
s,
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s and
carbohydrateCarbohydrates
[Means "hydrates of carbon"] or saccharides
[The word comes from the Greek σάκχαρον, sákcharon, meaning "sugar").] are the most abundant of the four major classes of biomolecules...
s may cause poorly digestible products to enter into the
colonThe colon is the last portion of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body....
. This can cause diarrhea by the
osmotic driveOsmosis is the diffusion of water through a semi-permeable membrane. More specifically, it is the movement of water across a semi-permeable membrane from an area of high water potential to an area of low water potential...
of these molecules, but can also stimulate the secretory mechanisms of colonic cells, leading to a
secretory diarrhea.
Risk factors and causes
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
motilityMotility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. It can apply to either single-celled or multicellular organisms. Motile marine animals are commonly called free-swimming...
or movement of the small bowel or anatomical changes that lead to
stasisIn medicine, stasis is the state in which the normal flow of a body liquid stops, for example the flow of blood through vessels or of intestinal contents through the digestive tract....
, (2) disorders in the
immune systemAn immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
and (3) conditions that cause more bacteria from the
colonThe colon is the last portion of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body....
to enter the small bowel.
Problems with motility may either be diffuse, or localized to particular areas. Diseases like
sclerodermaSystemic scleroderma is a systemic connective tissue disease.It is also known as "systemic sclerosis".-Skin symptoms:In the skin, scleroderma causes hardening and scarring. The skin may appear tight, reddish or scaly. Blood vessels may also be more visible. Where large areas are affected, fat and...
and possibly celiac disease cause diffuse slowing of the bowel, leading to increased bacterial concentrations. More commonly, the small bowel may have anatomical problems, such as out-pouchings known as diverticula that can cause bacteria to accumulate. After surgery involving the
stomachIn most mammals, the stomach is a hollow, muscular organ of the gastrointestinal tract , between the esophagus and the small intestine. It is involved in the second phase of digestion, following mastication . The word stomach is derived from the Latin stomachus, which derives from the Greek word...
and
duodenumThe duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
(most commonly with
Billroth IIBillroth II, more formally Billroth's operation II, is an operation in which the lower part of the stomach is removed and a loop of small bowel is brought up and joined to it in a for drainage ....
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.
Disorders of the immune system can cause bacterial overgrowth. Chronic
pancreatitisPancreatitis is inflammation of the pancreas that can occur in two very different forms. Acute pancreatitis is sudden while chronic pancreatitis "is characterized by recurring or persistent abdominal pain with or without steatorrhea or diabetes mellitus."...
, or inflammation of the
pancreasThe pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as an exocrine gland, secreting pancreatic juice containing digestive enzymes that pass to...
can cause bacterial overgrowth through mechanisms linked to this. The use of
immunosuppressantAn immunosuppressant is any substance that performs immunosuppression of the immune system. They may either be exogenous, as immunosuppressive drugs, or endogenous, as e. g. testosterone...
medications to treat other conditions can cause this, as evidenced from animal models. Other causes include inherited immunodeficiency conditions, such as combined variable immunodeficiency, IgA deficiency, and
hypogammaglobulinemiaHypogammaglobulinemia is a type of immune disorder characterized by a reduction in all types of gamma globulins.It is distinguished from dysgammaglobulinemia, which is a reduction in some types of gamma globulins, but not others....
.
Finally, abnormal connections between the
bacteriaThe bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
-rich colon and the small bowel can increase the bacterial load in the small bowel. Patients with
Crohn's diseaseCrohn's disease is an inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from anus to mouth, causing a wide variety of symptoms...
or other diseases of the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
may require surgery that removes the ileo-cecal valve connecting the small and large bowel; this leads to an increased reflux of bacteria into the small bowel.
After
bariatric surgeryBariatric surgery, or weight loss surgery, is a type of procedure performed on people who are dangerously obese, for the purpose of losing weight...
for obesity, connections between the stomach and the
ileumThe ileum is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may be used instead of ileum.The ileum follows the duodenum...
can be formed, which may increase bacterial load in the small bowel.
Proton pump inhibitorProton pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
medications that decrease acid in the
stomachIn most mammals, the stomach is a hollow, muscular organ of the gastrointestinal tract , between the esophagus and the small intestine. It is involved in the second phase of digestion, following mastication . The word stomach is derived from the Latin stomachus, which derives from the Greek word...
cause bacterial overgrowth by a similar mechanism, as they prevent the anti-bacterial effects of acid in the stomach. The clinical significance of this in causing symptoms is unclear.
Diagnosis
The diagnosis of bacterial overgrowth can be made by physicians in various ways.
MalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
can be detected by a test called the
D-xylose test.
XyloseXylose , or wood sugar, is an aldopentose — a monosaccharide containing five carbon atoms and including an aldehyde functional group. It has chemical formula 5105. Xylose is found in the embryos of most edible plants. It was first isolated from wood by Koch...
is a sugar that does not require enzymes to be digested. The D-xylose test involves having a patient to drink a certain quantity of D-xylose, and measuring levels in the
urineUrine is a liquid waste product of the body secreted by the kidneys by a process of filtration from blood called urination and excreted through the urethra. Cellular metabolism generates numerous waste compounds, many rich in nitrogen, that require elimination from the bloodstream...
and
bloodBlood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
; if there is no evidence of D-xylose in the
urineUrine is a liquid waste product of the body secreted by the kidneys by a process of filtration from blood called urination and excreted through the urethra. Cellular metabolism generates numerous waste compounds, many rich in nitrogen, that require elimination from the bloodstream...
and
bloodBlood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
, it suggests that the small bowel is not absorbing properly (as opposed to problems with enzymes required for digestion).
The gold standard for detection of bacterial overgrowth is the aspiration of more than 10
5 bacteria per millilitre from the small bowel. The normal small bowel has less than 10
4 bacteria per millilitre.
Breath tests have been developed to test for bacterial overgrowth, based on bacterial metabolism of carbohydrates to
hydrogenHydrogen is the chemical element with atomic number 1. It is represented by the symbol H. At standard temperature and pressure, hydrogen is a colorless, odorless, nonmetallic, tasteless, highly flammable diatomic gas with the molecular formula H
2...
, or based on the detection of by-products of digestion of carbohydrates that are not usually metabolized. The hydrogen breath test involves giving patients a load of carbohydrate (usually in the form of
riceRice is the seed of a monocot plant Oryza sativa, of the grass family . As a cereal grain, it is the most important staple food for a large part of the world's human population, especially in East, South, Southeast Asia, the Middle East, Latin America, and the West Indies...
) and measuring expired hydrogen concentrations after a certain time. It compares well to jejunal aspirates in making the diagnosis of bacterial overgrowth.
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
14C glychocholic acid, and the detection of
14CO
2, which would be elevated in bacterial overgrowth.
Some patients with symptoms of bacterial overgrowth will undergo gastroscopy, or visualization of the stomach and duodenum with an endoscopic
camerathumb |right|Cameras from Large to Small, Film to Digital A camera is a device that records images, either as a still photograph or as moving images known as videos or movies...
. 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
lymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.By their appearance under the light microscope, there are two broad categories of lymphocytes, namely the large granular lymphocytes and the small lymphocytes. Functionally distinct subsets of lymphocytes correlate with...
s in the
lamina propriaThe lamina propria is a constituent of the moist linings known as mucous membranes or mucosa, which line various tubes in the body ....
.
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.
Treatment
Bacterial overgrowth is usually treated with a course of antibiotics. A variety of antibiotics, including
neomycinNeomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments and eyedrops.-Uses:Neomycin is overwhelmingly used as a topical preparation, such as Neosporin. It can also be given orally, where it is usually combined with other antibiotics...
,
rifaximinRifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, meaning that very little of the drug will pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. It is used in the treatment of traveler's diarrhea and hepatic...
, amoxicillin-clavulanate, fluoroquinolone antibiotics and
tetracyclineTetracycline is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and more recently, rosacea, and played a historical role...
have been used; however, the best evidence is for the use of
norfloxacinNorfloxacin is a synthetic chemotherapeutic agent occasionally used to treat common as well as complicated urinary tract infections. It is sold under various brand names with the most common being Noroxin. In form of ophthalmic solutions it is known as Chibroxin. Norfloxacin is a second generation...
and amoxicillin-clavulanate.
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.
The condition that predisposed the patient to bacterial overgrowth should also be treated. For example, if the bacterial overgrowth is caused by
chronic pancreatitisChronic pancreatitis is a long-standing inflammation of the pancreas that alters its normal structure and functions. It can present as episodes of acute inflammation in a previously injured pancreas, or as chronic damage with persistent pain or malabsorption....
, the patient should be treated with coated pancreatic
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
supplements.
ProbioticProbiotics are dietary supplements of live microorganisms thought to be healthy for the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host"...
s are bacterial preparations that alter the bacterial flora in the bowel to cause a beneficial effect. Their role in bacterial overgrowth is somewhat uncertain.
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