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SIBO Breath Testing - Lactulose Challenge

The polymicrobial ecology created by a balanced human intestinal microbiota is characterized by broad diversity, high population density, and a complex web of interaction. When microbial dysbiosis occurs, serious health consequences, such as SIBO, may arise. Small intestinal bacterial overgrowth syndrome (SIBO) is a manifestation of Inflammatory Bowel Disease (IBD) characterized by excessive and/or abnormal microbiota in the small bowel (1).  SIBO is a condition with multiple factors contributing to development, including migration of bacteria from the large intestine into the small intestine, gastric secretion abnormalities, motility complications, and external factors including diet and activity level. Initially thought to affect only a small portion of the population, it is now becoming evident that more patients suffer from this poorly understood condition than previously believed.  Clinical presentation may range from mild gastrointestinal symptoms to chronic severe diarrhea and malabsorption issues. Non-invasive testing options are now available for patients from the comfort of home. This commentary will review the etiology, clinical testing and treatment options for SIBO.

  • Definition

    The microbiome in the GI tract is vast and dynamic. Unlike the large intestine which houses an abundant amount of microflora, the small intestine typically contains fewer micro-organisms. SIBO occurs when colony formation exceeds 103 organisms/mL. The overgrowth may be a mixture of beneficial (progenic) bacteria and harmful (pathogenic) bacteria. A mixture of anaerobic bacteria (Bacteroides, Lactobacillus, Clostridium) and aerobic bacteria (Streptococcus, Escherichia coli, Staphylococcus, Klebsiella, Proteus) have been documented. In addition to the absolute number of organisms, the type of microflora present will determine what signs and symptoms manifest clinically. For example, an overgrowth of bacteria that metabolize bile salts to insoluble compounds may lead to fat malabsorption and bile acid diarrhea. In contrast, microorganisms that preferentially metabolize carbohydrates to short-chain fatty acids and gas may produce bloating without diarrhea because the metabolic products can be absorbed (9). Identification of the species in excess is important for the proper treatment protocol.

Etiology

Some of the normal defenses to protect against bacterial growth in the human body include stomach acid, intestinal motility, intestinal integrity, and secretions (1).  When one (or more) of the endogenous defense mechanisms is compromised the conditions for potential bacterial overgrowth in the host increase. Etiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. In normal circumstances, gastric secretions prevent harmful bacteria from entering the small intestine. Hypochlorhydria (low stomach acid) due to aging, as well as using medications which suppress gastric acid secretion via histamine type 2 receptor blockers (H2RAs) or proton-pump inhibitors (PPIs) may predispose to SIBO. Normal gut motility is a highly orchestrated movement which carries food via peristalsis through the small intestine to the colon. In between meals and during periods of fasting, a migrating motor complex (MMC) develops approximately every 90-120 minutes to sweep metabolic byproducts and debris into the large intestine. Studies have shown that abnormalities in the MMC may predispose to the development of SIBO (3). SIBO causes damage to the mucosal lining in the gut triggering leaky gut syndrome and an inflammatory cascade.

Clinical Presentation

The clinical presentation of SIBO ranges from mild gastrointestinal symptoms to chronic severe diarrhea and malabsorption issues.  Common symptoms are bloating, diarrhea, malabsorption, abdominal pain, cramping, weight loss and malnutrition, while less common symptoms include constipation, nausea, heartburn, fatigue, excessive flatulence with strong sulfide gas odor, headaches, skin disorders, and joint pain.  A Vitamin B12 deficiency as well as iron deficiency anemia has also been documented in SIBO cases. SIBO may develop secondary to acute gastritis, chronic use of antibiotics, celiac disease, alcoholism, pancreatitis, neurodegeneration, hypochlorhydria, hypothyroidism, surgical gastric alterations, scleroderma, brain trauma, immunodeficiency and diabetes.  

  • Testing

    While the condition is complex, clinical testing advancements have improved our ability to identify the presence and severity of SIBO.  The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates.  Direct testing for the presence of SIBO using endoscopy can be expensive and invasive, so breath testing for overgrowth has become the predominant method due to its simplicity and ease of testing. These non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO, but do not identify the predominant species in overgrowth. These breath tests rely on the recovery and quantification of an exhaled gas produced by the bacterial metabolism of the ingested substrate, typically glucose or lactulose.  The presence and severity of SIBO is identifiable by the type of gas exhaled (methane or hydrogen) over a measured time period.  Neurogistics uses a Lactulose challenge test made by BioHealth Laboratories that measures a baseline breath test followed by consumption of a small lactulose solution.* Subsequent breath measurements are collected over a three hour period. Other clinical testing options for SIBO include urinary organic acid testing and stool analysis.

  • How to Address

    Depending on the severity of overgrowth, antibiotic therapy may be necessary to eliminate specific species in some cases. Generally, broad spectrum gastro-selective antibiotics are recommended for 2 weeks (amoxicillin, rifaximin, ciprofloxacin, etc.) but evidence for their use is fair (2). Reoccurrence rates of SIBO increase if other interventions are not included with antibiotic therapy.  Treatment for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualized. It should include treatment of the underlying disease as well as nutritional support. There are four stages of treatment 1) elimination/modification of the underlying causes (such as infections, food intolerances and gastric irritants), 2) Restore gastric function with digestive enzymes, bile salts, hydrochloric acid, etc.  3) Re-inoculate gut flora with progenic flora,  4) Repair mucosal barrier and residual inflammation using nutritional support such as L-glutamine, Vitamin D3, zinc, aloe vera, etc.  Diet modification is essential to reduce fermentable carbohydrate exposure. Fermentable carbohydrates include starch (grains, beans, starchy vegetables, seeds, legumes), soluble fiber, sugar (fruit, sweeteners), pre-biotics (agave, supplements, fermented foods, kefir, miso). Consider low FODMAP (Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols) foods in addition to eliminating sugar, grains, and starches.

*Disclaimer:

Lactulose is a synthetic sugar that is not digested in the gastrointestinal tract of humans, but small intestinal bacteria like it.   Because lactulose is used as a laxative, it can temporarily cause nausea, gas, bloating, and/or stomach pain, but many don’t experience these symptoms at all.  Before performing this test, it is important to note that there are a few contraindications that must be taken into consideration. Consult with your doctor if any of the below restrictions apply before taking this test:

- Lactulose contains galactose and should not be ingested by those following a galactose-free diet
- Lactulose should not be consumed prior to surgery
- While very small amounts of lactulose are absorbed into the body systemically, caution should be used if have a diagnosis of diabetes mellitus due to its sugar content.
- Pregnant or Nursing
 

References:

Bures, J Cyrany, J Kohoutova, D. Small intestinal bacterial overgrowth syndrome. World J Gastroenterology. 16(24): 2978-2990, 2010.

How to Test and Treat Small Intestinal Bacterial Overgrowth: an Evidence-Based Approach.  Current Gastroenterology Reports, 18:8, 2016.

Issacs PE, Kim YS. Blind loop syndrome and small bowel bacterial contamination. Clin Gastroenterol. 1983;12:395–414. 

Shindo K, Machinda M, Koide K, et al. Deconjugation ability of bacteria isolated from the jejunal fluid of patients with progressive systemic sclerosis and its gastric pH. Hepatogastroenterology. 1998;45:1643–1650.

Wanitschke R, Ammon HV. Effects of dihydroxy bile acids and hydroxyl fatty acids on the absorption of oleic acid in the human jejunum. J Clin Invest. 1978;61:178–186.

6Saltzman JR, Russell RM. Nutritional consequences of intestinal bacterial overgrowth. Comp Ther. 1994;20:523–530 

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