The pathogenesis of gastrointestinal bacterial overgrowth.

The normal indigenous intestinal microflora consists of about 10(15) bacteria that under physiological conditions reside mainly in the lower gastrointestinal tract. Bacterial overgrowth implies abnormal bacterial colonization of the upper gut, resulting from failure of specific defense mechanisms restricting colonization under physiological conditions. At present two types of bacterial overgrowth with defined pathogenesis can be distinguished: (1) gastric overgrowth with upper respiratory tract microflora resulting from selective failure of the gastric acid barrier, and (2) gastrointestinal overgrowth with Gram-negative bacilli (enteric bacteria) resulting from failure of intestinal clearance. Helicobacter pylori-induced gastritis of the oxyntic mucosa is the main cause of acquired failure of the gastric acid barrier, which is common among the healthy elderly. Intestinal clearance may fail as the result of impaired intestinal peristalsis or anatomical abnormalities that alter luminal flow. Impaired peristalsis is associated with conditions interfering with intestinal neuromuscular function including myopathic, neuropathic, autoimmune, infectious, inflammatory, metabolic, endocrine, and neoplastic diseases. Anatomical abnormalities are mainly the result of gastrointestinal surgery, intestinal diverticula or fistula. Combined failure of intestinal clearance and the gastric acid barrier results in more severe colonization with Gram-negative bacilli. Gram-negative bacilli are uncommon in the upper gut of otherwise healthy individuals with gastric hypochlorhydria, being acquired (H. pylori) or drug-induced. Significant bacterial overgrowth with Gram-negative bacilli is a rational in the search for an explanation to optimize clinical management. The clinical significance of colonization with upper respiratory tract microflora remains unclear. Translocation of live bacteria, their metabolic products, or antigens from a small bowel colonized by Gram-negative bacilli play a role in the pathogenesis of spontaneous bacterial peritonitis in hepatic disease and in certain types of sepsis, indicating that further studies can point to new patient populations with potential benefit from medical treatment.