Role of the Normal Flora in Disease

ROLE OF THE NORMAL FLORA IN DISEASE

Many species among the normal flora are opportunists in that they can cause infection if they reach protected areas of the body in sufficient numbers or if local or general host defense mechanisms are compromised. For example, certain strains of E. coli can reach the urinary bladder by ascending the urethra and cause acute urinary tract infection, usually in sexually active women. Perforation of the colon from a ruptured diverticulum or a pen-etrating abdominal wound releases feces into the peritoneal cavity; this fecal contamina-tion may be followed by peritonitis, caused primarily by facultative members of the flora, and by intraabdominal abscesses, caused primarily by Gram-negative anaerobes. Viridans streptococci from the oral cavity may reach the bloodstream as a result of physiologic trauma or injury (eg, tooth extraction) and colonize a previously damaged heart valve, ini-tiating bacterial endocarditis . These and other diseases, such as actino-mycosis, result from displacement of normal flora into body cavities or tissues.

Reduced specific immunologic responses, defects in phagocytic activity, and weaken-ing of epithelial barriers by vitamin deficiencies can all result in local invasion and dis-ease by normal floral organisms. This source accounts for many infections in patients whose defenses are compromised by disease (eg, diabetes, lymphoma, and leukemia) or by cytotoxic chemotherapy for cancer. One specific local infection of this type is Vin-cent’s angina of the oral mucosa, a local invasion and ulceration apparently caused by the combined action of oral spirochetes and members of the genus Fusobacterium. Death af-ter lethal radiation exposure usually results from massive invasion by normal floral organ-isms, particularly those of the intestinal tract. Caries and periodontal disease are both caused by organisms that are members of the normal flora.

Early in the 20th century, it was widely believed that the normal flora of the large in-testine was responsible for many “toxic conditions,” including rheumatoid arthritis, degenerative diseases, and a range of conditions now recognized as psychosomatic. Ritu-alistic purging and colonic lavage flourished, particularly at expensive mineral spas. At the height of this misdirected attack on the normal flora, some London patients were even subjected to colectomy as a cure for thyroid nodules. These notions persist in the form of the alleged beneficial effect of enemas and colonic lavages.

However, more recently, attention has again been focused on the less specific contribu-tions of the normal flora to health and disease. In patients with large or multiple blind-ended diverticula in the small intestine, heavy colonization by the anaerobic intestinal flora may occur. This colonization results in bacterial deconjugation of bile salts needed for absorption of fat and fat-soluble vitamins and also in competition for vitamin B₁₂. Similar situations sometimes occur in the elderly when the small intestine is invaded by colonic flora. If the primary cause cannot be eliminated surgically, these conditions can be amelio-rated with antibiotic therapy and fat-soluble vitamin supplements. An analogous situation occurs in tropical sprue, in which secondary colonization of the jejunum by facultative Gram-negative enteric bacteria leads to fat malabsorption and vitamin B₁₂ and folic acid deficiencies. It has been postulated that the higher colon cancer rates in those consuming Western as opposed to Asian diets may be a result of greater production by members of the normal flora of carcinogens such as nitrosamines and bile acid derivatives.

Under certain conditions, a “toxemia” can result from the action of the normal colonic flora. In severe hepatic cirrhosis, the portal circulation may be partially diverted to the sys-temic circulation. The detoxification by the liver of ammonia produced by bacterial action on protein residues is bypassed, and severe dysfunctions of the central nervous system (hepatic encephalopathy) can result. This problem can be ameliorated with a strict low-protein diet.