close
Bacterial overgrowth syndrome

Bacterial overgrowth syndrome

Bacterial overgrowth syndrome is a term that describes clinical manifestations that occur when the normally low number of bacteria that inhabit the stomach, duodenum, jejunum, and proximal ileum significantly increases or becomes overtaken by other pathogens 1.

The upper intestinal tract was once thought to be a sterile environment; however, low concentrations of various bacteria are now widely accepted to live within or attached to its luminal surface. These bacteria are thought to be present from the time of birth and through adulthood, living in symbiosis with the human host. This relationship is thought to be vital for normal digestive processes, immunity, and intestinal development. Bacterial species usually present include lactobacilli, enterococci, oral streptococci, and other gram-positive aerobic or facultative anaerobes.

Bacterial overgrowth syndrome can lead to worsening symptoms of malabsorption and diarrhea. In certain patient subgroups, bacterial overgrowth syndrome can lead to significant morbidity or death. However, exact mortality rates directly linked to bacterial overgrowth syndrome are not readily available.

Patient populations at an increased risk of mortality due to bacterial overgrowth syndrome include the following:

  • Neonates and young infants who are already malnourished or have congenital gastrointestinal abnormalities
  • Elderly patients with multiple medical problems and those who have underlying chronic diarrhea without known bacterial overgrowth syndrome
  • Patients who have undergone prior upper intestinal surgery that alters the protective mechanisms that prevent bacterial overgrowth syndrome
  • Patients with poor nutritional status at presentation
  • Patients with underlying medical conditions such as diabetes and scleroderma, who are at risk for relapse if the underlying medical condition is not corrected or managed

Various etiological processes can disrupt mechanisms that keep the number of these bacteria low. These include structural abnormalities (congenital or surgical) and disorders that cause decreased gastric acidity, reduced peristaltic activity, and mucosal damage or atrophy. The clinical manifestations of bacterial overgrowth syndrome stem from the increased bacterial burden on the normal functions of the upper gastrointestinal system. Prompt recognition and treatment of bacterial overgrowth syndrome should be targeted to prevent and reverse malabsorptive processes.

Bacterial overgrowth syndrome causes

Disorders or structural abnormalities that disrupt the protective mechanisms that guard against increasing bacterial burden can lead to bacterial overgrowth syndrome.

Patients with the following medical conditions are at increased risk for bacterial overgrowth syndrome:

  • History of upper intestinal tract surgery
  • Irritable bowel syndrome 2
  • Liver cirrhosis 2
  • Celiac disease 3
  • Immune deficiency (eg, AIDS, IGA deficiency, severe malnutrition) 2
  • Short bowel syndrome 4
  • End stage renal disease 2
  • Gastrojejunal anastomosis
  • Vagotomy, but not selective parietal cell vagotomy
  • Antral resection
  • Pancreatic exocrine insufficiency

Abnormal small intestinal motility due to the following may result in bacterial overgrowth syndrome:

  • Diabetic autonomic neuropathy
  • Scleroderma
  • Pseudo-obstruction
  • Amyloidosis
  • Neurological diseases (eg, myotonic dystrophy, Parkinson disease)
  • Radiation enteritis 4
  • Crohn disease 4
  • Hypothyroidism

Blind pouches from the following may result in bacterial overgrowth syndrome:

  • Side-to-side or end-to-side anastomoses
  • Intra-abdominal reservoirs
  • Duodenal or jejunal diverticula
  • Segmental dilatation of the ileum
  • Blind loop syndrome
  • Biliopancreatic diversion
  • Chagasic megacolon

Abnormal bowel communication due to the following may cause bacterial overgrowth syndrome:

  • Gastrocolic fistulae
  • Jejunal-colic fistulae

Partial obstruction caused by the following may result in bacterial overgrowth syndrome:

  • Strictures
  • Adhesions
  • Abdominal masses
  • Leiomyosarcoma

Reduced gastric acid secretion from the following may result in bacterial overgrowth syndrome:

  • Achlorhydria
  • Vagotomy
  • Long-term administration of proton pump inhibitors 5

Prevalence of bacterial overgrowth syndrome rises with age 2.

Bacterial overgrowth syndrome pathophysiology

Normally, colony counts of gram-positive bacteria and fungi in the duodenum and jejunum are less than 100,000 organisms/mL. Anaerobic bacteria are not found in the jejunum in healthy people. As many as one third of jejunal aspirates may be sterile in healthy people. Aerobic and anaerobic bacterial colony counts in the ileum are usually less than 1 X 108 organisms/mL. This is in sharp contrast to the 1 X 1011 organisms/mL that colonize the colon. Prevalence of bacteria in different parts of gastrointestinal tract depends on several factors such as peristalsis, pH, redox potential, bacterial adhesion, bacterial cooperation and antagonism, mucin secretion, diet, and nutrient availability 6.

Studies of duodenal aspirates have not identified any particular bacteria as a cause of bacterial overgrowth syndrome. However, 1 X 1011 organisms/mL of aspirate fluid is diagnostic for bacterial overgrowth syndrome. Cultures grown from patients with bacterial overgrowth syndrome reveal abnormally large numbers of anaerobic bacteria in addition to normal flora.

Several protective factors stabilize the number and type of bacteria that colonize the upper gastrointestinal tract. Abnormalities in these mechanisms predispose to bacterial overgrowth.

Two coordinated motor phenomena produce the continuous propulsive peristaltic action of the upper gastrointestinal tract. Both the migrating motor complex and the migrating action potential complex clear the upper intestine of unwanted bacteria and undigested substances. Desynchronization of these complexes results in diarrhea and weight loss in animal models. Anatomical defects can reduce peristaltic efficacy; for example, blind pouches result in a stagnant portion of the intestine.

Gastric acid and bile destroy many micro-organisms before they leave the stomach.

Enzymatic activity of intestinal, pancreatic, and biliary secretions help destroy bacteria in the small intestine 4.

The bowel mucosal integrity and mucin layer protect the gut from bacteria.

Immunoglobulin secretion and immune cells (eg, macrophages and lymphocytes) protect the gut from bacteria.

Normal intestinal flora (eg, Lactobacillus) protects the gut from bacterial overgrowth by maintaining a low pH; however, normal flora can facilitate an abnormal intraluminal environment. Abnormal communications produce pathways that allow enteric bacteria to pass between the proximal and distal bowel.

Ileocecal valve prevents retrograde translocation of bacteria from colon to the small intestine 4.

Malabsorption of bile acids, fats, carbohydrates, proteins, and vitamins results in direct damage to the lining of the luminal surface by bacteria or by transformation of nutrients into toxic metabolites, leading to many of the symptoms of diarrhea and weight loss associated with bacterial overgrowth syndrome. This leads to decreased function of the enterocytes within the intestinal lining and subsequent malabsorption. Diarrhea is potentiated by unabsorbed food products stimulating secretory cells within the colon.

Anaerobes such as Bacteroides fragilis actively deconjugate bile acids, thereby preventing proper bile acid function and enterohepatic circulation.

Fatty acid absorption is reduced because deconjugated bile acids cannot form micelles.

Deconjugated bile acids directly inhibit carbohydrate transporters. These unabsorbed sugars ferment into organic acids, thereby reducing the intraluminal pH and producing osmotic diarrhea. The unconjugated bile acids also damage intestinal enterocytes and induce water secretion by the colonic mucosa.

Loss of bile acids in the stool reduces the bile acid pool.

Bacterial overgrowth syndrome symptoms

No specific symptoms are pathognomonic for bacterial overgrowth syndrome. Nonetheless, various nonspecific gastrointestinal symptoms are common in affected individuals. Clinicians should have a heightened clinical suspicion for bacterial overgrowth syndrome in patients who present with the following:

  • Bloating
  • Flatulence
  • Abdominal pain
  • Diarrhea
  • Dyspepsia
  • Weight loss

Advanced cases of bacterial overgrowth syndrome may manifest as malabsorption findings, as follows:

  • Microcytic anemia due to iron deficiency
  • Macrocytic anemia due to vitamin B-12/folate deficiency
  • Polyneuropathy due to vitamin B-12 deficiency
  • Steatorrhea due to lipid malabsorption
  • Tetany due to hypocalcemia
  • Night blindness due to vitamin A deficiency
  • Dermatitis due to selenium deficiency
  • Bacterial overgrowth syndrome has been linked to rosacea 7
  • Cachexia due to protein-energy malnutrition

Bacterial overgrowth syndrome complications

Complications of bacterial overgrowth syndrome are possible in patients with prolonged and untreated symptoms, potentially leading to increased morbidity and mortality in higher-risk patients (eg, the very young and elderly).

Malabsorption of iron, vitamin B-12, and folate can lead to anemia

Persistent diarrhea can lead to volume loss and electrolyte disturbances.

Decreased fat absorption can lead to further diarrhea.

Bacterial overgrowth syndrome diagnosis

Bacterial overgrowth syndrome diagnostic testing should include a workup for diarrhea, anemia, and malabsorption. In the past, retrieval of aspirates from the small intestine itself during endoscopy was the diagnostic tool of choice; however, its use was limited due to low specificity.

Standard anemia workup and nutritional evaluation are indicated.

Stool analysis can help detect abnormal stool components. The pH may be acidic, and reducing substance may be present in the stool.

D-lactic acidosis syndrome can result from carbohydrate fermentation. Lactic acid levels may need to be measured and, if elevated, monitored. D-lactic acid levels, measured in the blood or urine, can help differentiate bacterial overgrowth syndrome from other metabolic causes.

Short-chain fatty acid levels may be elevated in the duodenal fluid but not the stool 8. Abnormal duodenal short-chain fatty acid levels average approximately 1 µmol/mL, with acetic acid, propionic acid, and n -butyric acid representing 61%, 16%, and 8% of the total, respectively. The average short-chain fatty acid level in a healthy patient is 0.27 µmol/mL, with acetic acid representing 84% of the total.

Keto-bile acid concentration in duodenal fluid is increased and correlates with the type of bacterial overgrowth 9. The molar percent of keto-bile acids in normal duodenal fluid is very close to 0, while gram-negative aerobic and anaerobic overgrowth is associated with levels of 32 µmol/mL and 11 µmol/mL, respectively.

Urine 4-hydroxyphenylacetic acid levels may be elevated 10. Enteric bacteria that possess L-amino acid decarboxylase produce 4-hydroxyphenylacetic acid from dietary tyrosine. Increased excretion has been demonstrated in adults with bacterial overgrowth syndrome. Creatinine levels that exceed 120 mg/g are typical in children with small-bowel disease or bacterial overgrowth syndrome, including children with chronic Giardia lamblia gastroenteritis. Children with severe pancreatic dysfunction secondary to cystic fibrosis also have significantly high levels of this metabolite. A 2% false-positive rate and no false-negative results are found when this test is used to screen healthy control subjects and hospitalized children.

Breath tests are used to measure byproducts of bacterial metabolism to identify malabsorbed substances 11. Several studies suggest that 3 breath tests are of adequate specificity, but these studies are not in full agreement regarding the exact sensitivity. Studies that compare these tests with duodenal bacterial counts suggest that the xylose breath test yields the highest specificity 12.

A carbohydrate breath test is a noninvasive, fast, and inexpensive test 13. The test uses the principle that the metabolism of either lactulose or glucose as its carbohydrate substrate by bacteria will produce either hydrogen or methane. This product will then be absorbed and excreted in the patient’s breath 14. A rise of more than 20 parts per million from baseline in hydrogen within 90 minutes or a methane level of more than 10 parts per million are positive results 14.

Imaging Studies

Evaluation for malabsorptive processes should include small-bowel follow-through, which is used to evaluate structure and mobility. Strictures, malrotation, diverticulosis, fistulae, and pseudo-obstruction can be found with this technique.

Imaging and examination of the lower gastrointestinal tract should be considered if upper gastrointestinal evaluation is nondiagnostic.

Bacterial overgrowth syndrome treatment

Treatment in bacterial overgrowth syndrome should include correction of primary underlying disease if any, including antibiotic therapy and nutritional support. The primary approach should be the treatment of any disease or anatomic defect that potentiated bacterial overgrowth. Many of the clinical conditions associated with bacterial overgrowth syndrome are not readily reversible, and management is based on antibiotic therapy aimed at rebalancing enteric flora. Careful consideration must be taken to prevent total eradication of protective microorganisms. The goal should be directed at reducing symptoms. Initial antibiotic therapy is usually empiric and should be broad and cover both aerobic and anaerobic microorganisms. Community resistance patterns should also be considered.

Tetracycline was the mainstay of therapy, but its use as single agent has fallen out of favor in adult patients given community increases in bacterial resistance.

Bacterial sensitivities from duodenal intubations with nonidiopathic bacterial overgrowth syndrome support the use of amoxicillin-clavulanate. Amoxicillin-clavulanate appears to be 75% effective in patients with diabetes.

Studies show that rifaximin eradicates bowel overgrowth syndrome in as many as 80% of patients 15. Higher doses (1200 or 1600 mg/d) are more effective then standard doses (600 or 800 mg/day) 16. Long-term favorable clinical results have been achieved with rifaximin in patients with irritable bowel and bacterial overgrowth syndrome 17.

Clindamycin and metronidazole are useful in elderly patients with idiopathic bacterial overgrowth syndrome.

As outlined below, gentamicin, but not metronidazole, significantly improves intractable diarrhea in children younger than 1 year 18.

Cholestyramine reduces diarrhea in infants and neonates with intractable diarrhea 19. Infants with 10-25 days of severe persistent diarrhea for which a cause could not be found despite an extensive infectious and immunologic workup were treated with cholestyramine and gentamicin or metronidazole. Cholestyramine and gentamicin significantly reduced stool weight within 4-5 days of therapy but had mild detrimental effects on fat and nitrogen absorption.

Ciprofloxacin and metronidazole result in normalization of hydrogen breath tests in most patients with Crohn disease 20.

Norfloxacin, cephalexin, trimethoprim-sulfamethoxazole, and levofloxacin have been recommended for the treatment of bacterial overgrowth syndrome 21.

The exact length of therapy is not clearly defined; length of therapy should be tailored to symptom improvement. A single 7-10 day course of antibiotic may improve symptoms in 46-90% of patients with bacterial overgrowth syndrome 22. Recurrence following therapy is not uncommon and is more likely in elder patients, especially those with history of appendectomy and chronic proton pump inhibitor use. Patients with recurrent symptoms may need repeated (eg, the first 5-10 d of every month) or continuous use of cyclical antibiotic therapy 2.

Probiotic therapy results in bacterial overgrowth syndrome have been inconclusive and not generally recommended for general clinic use 23.

Therapeutic use of prokinetics in bacterial overgrowth syndrome due to motility disorders have been tried in many studies. Metoclopramide, cisapride, domperidone, erythromycin, tegaserod, and octreotide have been used; however, data suggest long-term effectiveness is limited 21.

Nutritional support with dietary modifications such as lactose-free diet, vitamin replacement, and correction of deficiencies in nutrients like calcium and magnesium should be an important part of bacterial overgrowth syndrome treatment, if applicable.

Certain potential underlying abnormalities are amenable to treatment, as follows:

  • Infectious diarrhea
  • Malnutrition
  • Malabsorption
  • Hypothyroidism
  • Inflammatory bowel disease
  • Immunodeficiency

The following potential underlying diseases are not amenable to treatment, but prevention of their progression may be therapeutic:

  • Diabetic autonomic neuropathy
  • Scleroderma
  • Pseudoobstruction
  • Amyloidosis
  • Achlorhydria
  • Vagotomy
References
  1. Bacterial overgrowth syndrome. https://emedicine.medscape.com/article/212861-overview
  2. Quigley EM, Abu-Shanab A. Small intestinal bacterial overgrowth. Infect Dis Clin North Am. 2010 Dec. 24(4):943-59, viii-ix.
  3. Rubio-Tapia A, Barton SH, Rosenblatt JE, Murray JA. Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease. J Clin Gastroenterol. 2009 Feb. 43(2):157-61.
  4. Bures J, Cyrany J, Kohoutova D, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010 Jun 28. 16(24):2978-90.
  5. Lewis SJ, Franco S, Young G, O’Keefe SJ. Altered bowel function and duodenal bacterial overgrowth in patients treated with omeprazole. Aliment Pharmacol Ther. 1996 Aug. 10(4):557-61.
  6. Hao WL, Lee YK. Microflora of the gastrointestinal tract: a review. Methods Mol Biol. 2004. 268:491-502.
  7. Parodi A, Paolino S, Greco A, Drago F, Mansi C, Rebora A. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008 Jul. 6(7):759-64.
  8. Hoverstad T, Bjorneklett A, Fausa O, Midtvedt T. Short-chain fatty acids in the small-bowel bacterial overgrowth syndrome. Scand J Gastroenterol. 1985 May. 20(4):492-9.
  9. Kocoshis SA, Schletewitz K, Lovelace G, Laine RA. Duodenal bile acids among children: keto derivatives and aerobic small bowel bacterial overgrowth [published erratum appears in J Pediatr Gastroenterol Nutr 1988 Jan-Feb;7(1):155]. J Pediatr Gastroenterol Nutr. 1987 Sep-Oct. 6(5):686-96.
  10. Chalmers RA, Valman HB, Liberman MM. Measurement of 4-hydroxyphenylacetic aciduria as a screening test for small-bowel disease. Clin Chem. 1979 Oct. 25(10):1791-4.
  11. Sherr HP, Sasaki Y, Newman A, et al. Detection of bacterial deconjugation of bile salts by a convenient breath-analysis technic. N Engl J Med. 1971 Sep 16. 285(12):656-61.
  12. Saad RJ, Chey WD. Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy. Clin Gastroenterol Hepatol. 2014 Dec. 12 (12):1964-72; quiz e119-20.
  13. Ghoshal UC, Ghoshal U, Das K, Misra A. Utility of hydrogen breath tests in diagnosis of small intestinal bacterial overgrowth in malabsorption syndrome and its relationship with oro-cecal transit time. Indian J Gastroenterol. 2006 Jan-Feb;25(1):6-10.
  14. Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, Schmulson M, Valdovinos M, Zakko S, Pimentel M. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am. J. Gastroenterol. 2017 May;112(5):775-784.
  15. Peralta S, Cottone C, Doveri T, Almasio PL, Craxi A. Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms: experience with Rifaximin. World J Gastroenterol. 2009 Jun 7. 15(21):2628-31.
  16. Scarpellini E, Gabrielli M, Lauritano CE, Lupascu A, Merra G, Cammarota G. High dosage rifaximin for the treatment of small intestinal bacterial overgrowth. Aliment Pharmacol Ther. 2007 Apr 1. 25(7):781-6.
  17. Frissora CL, Cash BD. Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome. Aliment Pharmacol Ther. 2007 Jun 1. 25(11):1271-81.
  18. Hill ID, Mann MD, Househam KC, Bowie MD. Use of oral gentamicin, metronidazole, and cholestyramine in the treatment of severe persistent diarrhea in infants. Pediatrics. 1986 Apr. 77(4):477-81.
  19. Tamer MA, Santora TR, Sandberg DH. Cholestyramine therapy for intractable diarrhea. Pediatrics. 1974 Feb. 53(2):217-20.
  20. Castiglione F, Rispo A, Di Girolamo E, Cozzolino A, Manguso F, Grassia R, et al. Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn’s disease. Aliment Pharmacol Ther. 2003 Dec. 18(11-12):1107-12.
  21. Vanderhoof JA, Young RJ. Etiology and pathogenesis of bacterial overgrowth. Clinical manifestations and diagnosis of bacterial overgrowth. Treatment of bacterial overgrowth UpToDate online, vol 18.1; Wellesley, 2010.
  22. Banwell JG, Sherr H. Effect of bacterial enterotoxins on the gastrointestinal tract. Gastroenterology. 1973 Sep. 65(3):467-97.
  23. Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics. Gastroenterology. 2006 Feb. 130(2 Suppl 1):S78-90.
Health Jade Team

The author Health Jade Team

Health Jade