SMALL INTESTINAL BACTERIAL OVERGROWTH
Small intestinal bacterial overgrowth (SIBO) is a syndrome in which there are excessive numbers of bacteria (more than 105 organisms per milliliter of intestinal contents) in the duodenum and jejunum in a fasting state.
This overproliferation of microflora can result in malabsorption and diarrhea. SIBO is well recognized in dogs and humans, but there are no reports of SIBO in cats.The normal small intestinal microflora consists of a small but stable population of aerobic and facultative anaerobic bacteria. Population size is influenced by factors such as the host's immune system, bacterial interactions, dietary composition, and the action of normal mechanisms that help to limit bacterial overgrowth (secretion of gastric acid, the dynamic process of intestinal motility and continuous aborad flow of ingesta, and antibacterial factors in pancreatic juice). Causes of overgrowth of bacteria may include anatomic factors such as obstruction (e.g., partial stricture, presence of a mass), segmental hypomotility, conditions associated with decreased secretion of gastric acid, intestinal mucosal disease, immunodeficiency states, and concurrent exocrine pancreatic insufficiency, or it may result from some unidentifiable cause. A state of immunodeficiency may be one of the reasons that SIBO might be more commonly diagnosed in German shepherds and shar-peis than in other breeds. These breeds appear to have a higher incidence of IgA deficiency. The most common problems in dogs with IgA deficiency are recurrent infections and atopic dermatitis. The infections associated with IgA deficiency are generally not severe or life threatening, and treatment is symptomatic.
Although any species of bacteria may be found, Escherichia coli, enterococci, and lactobacilli are more common in dogs. Obligate anaerobic species are rarely found in the proximal small intestine of the dog, whereas in cats there may be up to 105 to 108 bacteria per milliliter of fluid, commonly including obligate anaerobic bacteria such as Bacteroides, Eubacterium, and Fusobacterium.
In cats Pasteurella spp. are the most common bacteria isolated.The pathophysiology of SIBO is very complex and is related to both the effects of proliferation of bacteria in the intestinal lumen and direct damage to enterocytes. Potential mechanisms include direct injurious effects on brush border enzymes and carrier proteins, secretion of enterotoxins, deconjugation of bile acids, hydroxylation of fatty acids, and competition for nutrients.
The most common clinical signs of SIBO are diarrhea and weight loss.Vomiting, flatulence, and anorexia may also occur. Diarrhea is usually of small bowel type of consistency and may be watery to soft formed and malodorous. Stools may also be lighter in color than normal, but this is a nonspecific sign. Blood and mucus are usually not present (if they are, a large bowel disorder of any type should be considered). Other clinical signs that might be present occur as a result of a primary disorder (e.g., ravenous appetite associated with exocrine pancreatic insufficiency, decreased appetite, frequent vomiting, and lethargy associated with obstruction).
Diagnosis
Establishing a definitive diagnosis of SIBO is difficult in a private-practice setting. Ideally, quantitative duodenal fluid cultures should be done to determine if SIBO is present. This is difficult to do properly and is also expensive. Aliquots of duodenal fluid need to be obtained either at laparotomy or by using a sterilized endoscope to obtain samples from the small intestine. A positive response to antibiotics (e.g., amoxicillin, metronidazole, tetracycline, tylosin) for 2 to 4 weeks can be used as a presumptive diagnosis of SIBO.
The best screening tests for use in private practice involve serum analysis of fasting cobalamin (vitamin B12) and folate levels, although these tests are not regarded as very sensitive, because many affected dogs do not have abnormal test results. Abnormalities that suggest SIBO include elevated folate levels (due to increased production by abnormal microflora) and decreased cobalamin levels (due to utilization by microflora).
It is not common for this combination of results to be found. In many patients only one of the two tests is abnormal. In patients with SIBO that is not present in conjunction with exocrine pancreatic insufficiency, elevated folate level is found in approximately 50% of the cases, and decreased cobalamin level alone in about 25% of cases. These tests should be considered in any patient that has chronic diarrhea, including those with exocrine pancreatic insufficiency (these dogs commonly have SIBO). Cobalamin levels that are below the control range may also be consistent with disease affecting the distal small intestine (cobalamin is absorbed only in the last 25% of the distal small intestine). Folate levels below the control range may indicate infiltrative disease affecting the proximal small intestine (folate is absorbed in the proximal small intestine only).A new test for SIBO is serum unconjugated cholic acid (SUCA). Many of the species of bacteria that increase in number in SIBO have the capacity to unconjugate bile acids. Unlike the conjugated bile acids that are normally present in the small intestinal lumen, bile acids that are unconjugated diffuse across the intestinal mucosa into the blood. In dogs, SUCA values greater than 72 nm/L are suggestive of bacterial overgrowth or disturbance of the normal flora of the upper small intestine. The SUCA test is currently available at the Texas A&M University GI Lab.
The sample should be shipped overnight on ice, ideally on the same day on which the sample is obtained. Dogs should be fasted for 12 hours before sampling. When testing for SIBO, it is recommended that serum for cobalamin, folate, and SUCA assays should be run concurrently. Trypsinlike immunoreactivity (TLI) assay should be done as well if pancreatic exocrine insufficiency has not already been ruled out.
It is not uncommon for a dog with IBD to have SIBO as well. Intestinal biopsy specimens from patients with SIBO are normal or may show minimal morphologic mucosal changes.
Minor changes may include mild atrophy of villi and a slight increase in inflammatory cells. If intestinal biopsy samples in a dog or cat with chronic diarrhea are normal or exhibit only mild changes, the presence of SIBO should definitely be considered.Treatment
Treatment of SIBO involves use of selected antibiotics, and treatment time may vary from several weeks to many months. Some patients require intermittent treatment. Sometimes once-daily antibiotic administration is adequate in patients that require long-term therapy. Any identifiable causes should be removed (e.g., surgical removal of blind or stagnant loops of bowel). Antibiotics that have broad-spectrum effect that includes anaerobic bacteria are selected (amoxicillin, metronidazole, tetracycline, and tylosin are good choices). If there is a rapid response to therapy, an attempt to discontinue antibiotic administration can be made after 2 to 3 weeks.
If long-term antibiotic administration seems to be necessary, my preference is usually to use either metronidazole or tylosin powder. The recommended dose of tylosin is 5 to 10 mg/lb orally every 12 hours mixed with food. Tylosin powder has a bitter taste, and some dogs will accept it better if it is mixed in the food initially in very small amounts.
It is emphasized that concurrent problems may be present with SIBO, and even if the bacterial overgrowth is adequately treated, an underlying disorder not yet diagnosed and managed may itself cause persistence of clinical signs.