Introduction
Recognition that intestinal flora have a major impact on human health first developed with the birth of microbiology in the late nineteenth century. It is generally accepted that our relationship with indigenous gut flora is "Eu-symbiotic," meaning a state of living together that is beneficial. Metchinkoff popularized the idea of "Dys-symbiosis, or Dysbiosis," a state of living with intestinal flora thathas harmful effects. He postulated that toxic amines produced by bacterial putrefaction of food were the cause of degenerative diseases, and that ingestion of fermented foods containing Lactobacilli could prolong life by decreasing gut putrefaction(1). Although Metchnikoff's ideas have been largely ignored in the United States, they have influenced four generations of European physicians. The notion that dysbiotic relationships with gut microflora may influence the development of inflammatory diseases and cancer has received considerable experimental support over the past two decades, but the mechanisms involved are far more diverse than Metchnikoff imagined.

The stool of healthy human beings consuming a Western diet contains 24 x 105¡ bacteria/gram. Twenty species comprise 75% of the total number of colonies; non-spore forming anaerobes predominate over aerobes by a ratio of 5000:1(2). Organisms cultured from mucosal surfaces are significantly different from those found in stool and vary among different parts of the gastrointestinal tract. The bacterial concentration in the stomach and small intestine is several orders of magnitude less than in the colon. The major mucosal organisms there are coccobacilli(1) and streptococci(3). The predominant organisms cultured from gastric and duodenal aspirates, are yeasts and Lactobacilli(2), living in the lumen. In the colon, the presence of these organisms is overshadowed by spirochetes and fusfform bacteria on the mucosal surface and anaerobic rods like Eubacterium, Bacteroides and Bifidobacterium in the lumen. Benefits and adverse effects of the normal gut microflora are listed in Table 1 & 2 and have been described elsewhere(4).

Materials and Methods

Clinical Assessment
lntestinal dysbiosis should be considered as a mechanism promoting disease in all patients with chronic gastrointestinal, inflammatory or autoimmune disorders, food allergy and intolerance, breast and colon cancer, and unexplained fatigue, malnutrition or neuropsychiatric symptoms.

The most useful test for this condition is a Comprehensive Digestive Stool Analysis (CDSA) which includes:

a) biochemical measurements of digestion/maldigestion (fecal chymotrypsin, fecal triglycerides, meat and vegetable fibers, pH), intestinal absorption/ malabsorption (long chain fatty acids, fecal cholesterol, and total short chain fatty acids)
b) metabolic markers of intestinal metabolism
c) identification of the bacterial microflora, including friendly, pathogenic and imbalanced flora
d) detection of abnormal gut mycology

The authors have developed a Gut Dysbiosis Score (Table 3) to make the CDSA more useful.

Interpretation of Gut Dysbiosis Score (Refers to Table 3)

Excess meat or vegetable fibers or triglycerides (one point each) suggest mal- digestion. This is a common effect of bacterial overgrowth but can also con- tribute to its cause.

Excess cholesterol or fatty acids (one point each) is indicative of malabsorp- tion; bacterial overgrowth produces this by interfering with micelle forma- tion.

Low concentrations of butyrate or SCFA (two points each) indicate insuffi- cient anaerobic fermentation of soluble fiber. This may result from a low fiber diet deficiency of Bifidobacteria.

High concentrations of butyrate or SCFA (two points each) is indicative of increased anaerobic fermentation.

Alkaline stool pH (two points) often accompanies a low butyrate. When it is associated with a normal butyrate it signifies increased ammonia production, reflecting a diet high in meat or excessive urease activity of intestinal bacte- ria. Bacterial cultures can provide more direct evidence of dysbiosis. The most common finding is:

A lack of Lactobacillus or of E.Coli on stool culture (3 points each) High levels of uncommon or atypical Enterobacteriaceae or of Klebsiella, Proteus or Pseudomonas, may reflect small bowel overgrowth of these organisms (score 1 point for each.)

Total Score-7 points or more is always associated with clinical dysbiosis; 5-6 is probable dysbiosis; 3-4 is borderline. There are rare cases in which a score less than 3 occurs in a dysbiotic stool. These cases are usually under treatment at the time the stool is obtained. In severe cases abnormal blood tests may be found. There may be erythrocyte macrocytosis, low circulating vitamin B12 or hypoalbuminemia. Urinary excretion of essential amino acids may also be low, signifying impaired assimilation of dietary protein.

Discussion
Based on available research and clinical data, we now believe that there are four patterns of intestinal dysbiosis: putrefaction, fermenta- tion, deficiency, and sensitization.

Putrefaction
This is the classic Western degenerative disease pattern advanced by Metchnikoff. Putrefaction dysbiosis results from diets high in fat and animal flesh and low in insoluble fiber. This type of diet produces an increased concentration of Bacteroides sp. and a decreased concentra- tion of Bifidobacteria sp. in stool. It increases bile flow and induces bacterial urease activity(1). The alterations in bacterial population dynamics which result from this diet are not measured directly by the [Comprehensive Digestive Stool Analysis (CDSA)]. The changes occur primarily among anaerobes, but the effects are measured in an in- crease in stool pH (partly caused by elevated ammonia production) and in bile or urobilinogen and possibly by a decrease in short chain fatty acids, especially in butyrate. Epidemiologic and experimental data implicate this type of dysbiosis in the pathogenesis of colon can- cer and breast cancer(6). A putrefaction dysbiosis is accompanied by an increase in fecal concentrations of various bacterial enzymes which metabolize bile acids to tumor promotors and deconjugate ex- creted estrogens, raising the plasma estrogen level(6). Putrefaction dysbiosis is corrected by decreasing dietary fat and flesh, increasing fiber consumption and feeding Bifidobacteria and Lactobacillus prep- arations.

Most adverse effects of the indigenous gut flora are caused by the intense metabolic activity of luminal organisms. The following are associated with Putrefaction dysbiosis:

1. The enzyme urease, found in Bacteroides, Proteus and Klebsiella species, and induced in those organisms by a diet high in meat, hy- drolyzes urea to ammonia, raising stool pH. A relatively high stool pH is associated with a higher prevalence of colon cancer(7).

2. Bacterial decarboxylation of amino acids yields vasoactive and neurotoxic amines, including histamine, octopamine, tyramine and tryptamine; these are absorbed through the portal circulation and deaminated in the liver. In severe cirrhosis they reach the systemic circulation and contribute to the encephalopathy and hypotension of hepatic failure(1).

3. Bacterial tryptophanase degrades tryptophan to carcinogenic phe- nols, and, like urease, is induced by a high meat diet(8).

4. Bacterial enzymes like beta-glucuronidase hydrolyze conjugated es- trogens and bile acids. Hepatic conjugation and biliary excretion is an important mechanism for regulating estrogen levels in the body. Bacte- rial deconjugation increases the enterohepatic recirculation of estrogen. A Western diet increases the level of deconjugating enzymes in stool, lowers estrogen levels in stool and raises estrogen levels in blood and urine, possibly contributing to the development of breast cancer(6).

5. Beta-glucuronidase and other hydrolytic bacterial enzymes also deconjugate bile acids.

Deconjugated bile acids are toxic to the colonic epithelium and cause diarrhea. They or their metabolites appear to be carcinogenic and are thought to contribute to the development of colon cancer(6,9) and to ulcerative colitis(10). Gut bacteria also reduce primary bile acids like cholate and chenodeoxycholate to secondary bile acids like deoxycholate (DCA) and lithocholate. The secondary bile acids are ab- sorbed less efficiently than primary bile acids and are more likely to contribute to colon carcinogenesis. The prevalence of colon cancer is proportional to stool concentration of DCA.

Not all bacterial enzyme activity is harmful to the host. Fermenta- tion of soluble flber by Bifidobacteria sp. yields SCFA. Recent interest has focused on the beneficial role of short-chain fatty acids like buty- rate in nourishing healthy colonic mucosal cells. Butyrate has been shown to induce differentiation of neoplastic cells(l1), decreased ab- sorption of ammonia from the intestine(1), decreased inflammation in ulcerative colitis(12) and, following absorption, decreased cholesterol synthesis in the liver(7). Butyrate lowers the stool pH. A relatively low stool pH is associated with protection against colon cancer(S). The principal source of colonic butyrate is fermentation of soluble fiber by colonic anaerobes. Thus, putrefaction dysbiosis results from the inter- play of bacteria and diet in their effects on health and disease.

Fermentation
This is a condition of carbohydrate intolerance induced by overgrowth of endogenous bacteria in the stomach, small intestine and cecum. The causes and effects of small bowel bacterial overgrowth have been well characterized.

Bacterial overgrowth is promoted by gastric hypochlorhydria, by stasis due to abnormal motility, strictures, fistulae and surgical blind loops, by immune deficiency or by malnutrition( 13). Small bowel parasitosis may also predispose to bacterial overgrowth(4). Some of the damage resulting from small bowel bacterial overgrowth is pro- duced by the action of bacterial proteases which degrade pancreatic and intestinal brush border enzymes causing pancreatic insufficiency, mucosal damage and malabsorption. In more severe cases the intesti- nal villi are blunted and broadened and mononuclear cells infiltrate the lamina propria. Increased fecal nitrogen leads to hypoalbumine- mia. Bacterial consumption of cobalamin lowers blood levels of vita- min B12. Bile salt dehydroxylation impairs micelle formation(10). Endotoxemia resulting from bacterial overgrowth contributes to hep- atic damage in experimental animals(14).

Gastric bacterial overgrowth increases the risk of systemic infec- tion. Gastric bacteria convert dietary nitrates to nitrites and nitro- samines; hence, the increased risk of gastric cancer in individuals with hypochlorhydria( 15) . Some bacterial infections of the small bowel increase passive intestinal permeability(16).

Carbohydrate intolerance may be the only symptom of bacterial overgrowth, making it indistinguishable from intestinal candidosis; in either case dietary sugars can be fermented to produce endogenous ethanol(17,18). Chronic exposure of the small bowel to ethanol may itself impair intestinal permeability(19). Another product of bacterial fermentation of sugar is D-lactic acid. Although D-lactic acidosis is usually a complication of short-bowel syndrome or of jejuno-ileal by- pass surgery (colonic bacteria being the source of acidosis), elevated levels of D-lactate were found in blood samples of 1.12% of randomly selected hospitalized patients with no history of gastro-intestinal sur- gery or disease(20). Small bowel fermentation is a likely cause of D-lactic acidosis in these patients. British physicians working with the gut-fermentation syndrome as described by Hunisett et al(18) have tentatively concluded, based on treatment results, that the ma- jority of cases are due to yeast overgrowth and about 20% are bacte- rial in origin. The symptoms include abdominal distension, carbohy- drate intolerance, fatigue and impaired cognitive function.