Dietary fiber is well known to affect intestinal cell proliferation. Both high fermentation ratio and high viscosity are essential for this proliferative action. In our study, two possible mechanisms are suggested which may be responsible for the proliferative actions induced by pectin supplementation. One is a humoral factor, glucagon-like peptide 2, and the other is an effect of short chain fatty acids. Especially, butyrate, one of the short chain fatty acids, is produced in the cecum and colon by bacterial fermentation. Butyrate has anti-inflammatory effects as well as significant proliferative effects in the intestine, and a butyrate enema or oral administration of Clostridium butyricum M588, which produces butyrate in the cecum and colon, have significant therapeutic benefits on DSS colitis. Germinated barley foodstuff (GBF) is made from brewer's spent grain, and contains glutamine rich protein and hemicellulose. It has already been shown in animal models and chinical trials that GBF is effective for attenuating or maintaining ulcerative colitis, and GBF has been approred for chinieal use. Its therapeutic effects are associated with an increased fecal butyrate level. Furthermore, lectins also have proliferative effects on the intestine. In our present study, lectins were shown to attenuate some intestinal injury models, and may be beneficial as a treatment of inflammatory bowel disease.

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Increase and changes in intestinal microflora might enhance mucosal inflammation. Mucosal inflammation, once it begins, may impair intestinal motility by amplifying inflammatory reactions within the muscular layers. Because intestinal motility is considered to be an important factor for the maintenance of normal intestinal flora, there could be a "vicious cycle" created between changes in intestinal flora and motility in the intestine. This may result in the alteration of intestinal functions, which might lead to systemic diseases in advanced cases. We hypothesize that dysfunction of intestinal motility observed in the enterocolitis of Hirschsprung's disease may be attributable to substances originating from macrophages resident at the level of the myenteric plexus. We describe here the knowledge about the relationship between intestinal microflora and motility dysfunction in gut inflammatory diseases.

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Soy isoflavones are considered to have potentially beneficial effects for preventing Western diseases including hormone-dependent cancer and heart disease. In soybean and soy foods, glycoside forms of isoflavones are dominant over their aglycones, while aglycones are mostly dominant in fermented soy foods. As the glycoside forms of isoflavones are not absorbed intact, initial hydrolysis of the sugar moiety is required for their bioavailability. β-Glucosidase activity of the intestinal flora is thought to play a role in the hydrolysis of the glucosides of isoflavones. Absorbed soy isoflavones are conjugated in the liver and excreted into bile. They are deconjugated in the intestine and then go into enterohepatic circulation. The activity of β-glucuronidase of intestinal flora plays an important role in this deconjugation. Isoflavone aglycones are further metabolized in the intestine to either more estrogenic metabolites or inactive compounds. The metabolic activities of intestinal flora are essential for this metabolism of the isoflavones. Great inter-individual difference is reported in the production of these metabolites and the difference in the composition of intestinal flora is thought to be responsible for this variation. The variation in the metabolism of soy isoflavones might cause differences in the beneficial effects of soy foods. There are few reports on bacteria which are active in producing estrogenic metabolites.

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The gastrointestinal tract is colonized with more than 10¹⁴ microorganisms that weigh more than 1 kg. Such microbes are in close contact with the largest mass of lymphoid tissue in the body, the gut-associated lymphoid tissue, and thereby provide the principal driving force in postnatal maturation of the mammalian immune system. In addition to such effects, some previous studies have shown that psychological stress might disrupt the integrity of the intestinal microflora and thereafter contribute to the pathological process of gastrointestinal disorders. Recently, we demonstrated that postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. These results indicate a novel link between intestinal flora and the nervous system and show a new aspect of the brain-gut axis.

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To elucidate the effect of fermented milk containing Lactobacillus johnsonii La1 on human blood phagocytic activity, a double-blind placebo controlled cross-over trial was conducted. Twenty-seven healthy Japanese volunteers were randomly divided into 2 groups, and either of test fermented milk containing L. johnsonii La1 (1x10⁹ cfu /120 g) or placebo fermented milk without L. johnsonii La1 was administered daily for 21 days. At the end of the first period, blood phagocytic activity in the subjects administered test fermented milk increased significantly compared to that of before intake. Although phagocytic activity in the subjects administered placebo fermented milk also increased, the activity was low compared to that of the subjects administered test fermented milk. Blood phagocytic activities in the both groups were maintained at high levels after the 29 days wash-out period. At the end of the second period, phagocytic activity in the subjects administered test fermented milk was significantly higher than before intake. For confirmation of safety against excess dosage, 3 cups (360 g)/day of the test fermented milk was administered to 10 healthy persons for 14 days. Blood phagocytic activity significantly increased after administration of test fermented milk, and no adverse effects were observed in the medical check-up, blood and urine tests. These results suggest that ingestion of fermented milk containing L. johnsonii La1 is effective at reinforcing the natural immune system of humans without any safety concerns for excessive administration.

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