Bifidobacteria are the predominant lactic acid bacteria of the colon with a concentration that is 1000 times higher than Lactobacilli. Ad- ministration of Bifidobacterium brevum to humans and animals re- duces fecal concentrations of Clostridia and Enterobacter species, am- monia, and toxigenic bacterial enzymes including beta-glucuronidase and tryptophanase; urinary indican is also lowered(59). Administra- tion of defined strains of E. coli and Enterococcus for the purpose of altering gut flora has been popular in Europe, but documentation of the health effects is scanty.

Bacillus laterosporus, a novel organism classified as non patho- genic to humans(60), produces unique metabolites with antibiotic, anti-tumor and immune modulating activity(61-63). This organism has been available as a food supplement in the United States for about 5 years. We have found it to be an effective adjunctive treat- ment for control of symptoms associated with small bowel dysbiosis in a number of patients.

Of equal interest, and more thoroughly researched, a yeast, Sac- charomyces boulardii, has been used in Europe for control of non- specific diarrhea for several decades. Originally isolated from Indo- chinese leechee nuts, S. boulardii is grown and packaged as a medica- tion in France, where it is popularly called, "Yeast Against Yeast". Controlled studies have demonstrated its effectiveness in preventing antibiotic associated diarrhea and Clostridium difficile colitis(64,65). S. boulardii has also been shown to stimulate production of secretory IgA in rats(66). Immune enhancing therapy of this type may be con- traindicated in patients suffering from reactive arthritis and other diseases in which an exaggerated intestinal immune response is found.

Antimicrobials
Antibiotic drugs may either cause or help control dysbiosis, depend- ing upon the drug and the nature of the disorder. Where contamina- tion of the small bowel by anaerobes is the problem, metronidazole or tetracyclines may be beneficial. When enterobacterial overgrowth predominates, ciprofloxacin is usually the drug of choice because it tends to spare anaerobes. Herbal antibiotics may be preferred because of their greater margin of safety and the need for prolonged anti- microbial therapy in bacterial overgrowth syndromes. Citrus seed ex- tract may be a desirable first line of treatment because of its broad spectrum of antibacterial, anti-fungal and anti-protozoan effects(23). The usual dose required is 600 to 1600 mg/day. Animal studies have shown no toxicity except for intestinal irritation producing diarrhea at very high doses. The mechanism of action is not known; there is no evidence of systemic absorption. Bayberry leaf, containing the alka- loid berberine, appears to be cidal for enterobacteria, yeasts and amoebae. The control of dysbiotic symptoms usually requires several grams a day. Artemesia annua has primarily been used for treatment of protozoan infection(67). The most active ingredient, artemisinin, is a potent pro-oxidant whose activity is enhanced by polyunsaturated fats like cod liver oil and antagonized by vitamin E.(68). Artemisinin is used intravenously in Southeast Asia for the treatment of cerebral malaria; it has no known side effects except for induction of abortion when used at high doses in pregnant animals.

The herbal pharmacopeia lists many substances with natural anti- biotic activity and the potential for herbal treatment of gut dysbiosis is virtually unlimited. A tannin-rich mixture of herbal concentrates including extracts of gentiana, sanguinaria and hydrastis has been marketed under various names. In vitro studies at Great Smokies Di- agnostic Laboratory have found this mixture to exert more potent ac- tivity against enterobacteriaceae and Staphylococcus than any of the common antibiotic drugs tested; its major side effect is nausea pro- duced by the high tannin content.