Nitric oxide is produced by numerous cell types along the GI tract where it serves to regulate a variety of physiological processes including gut motility, secretions, mucosal blood flow and immunity. Classically, NO is produced from L-arginine and molecular oxygen by specific enzymes, the NO synthases, but more recently a fundamentally different pathway for NO generation was described. This involves stepwise reduction of the higher nitrogen oxides nitrate and nitrite to form NO. In this process commensal bacterial in the GI tract play a key role. Dietary nitrate (mainly provided for by vegetables) accumulates in saliva and the oral microflora reduces this nitrate to nitrite. Nitrite then enters the stomach where it is reduced to NO by the acid. A picture is now emerging suggesting an important role of entero-salivary circulation of nitrate and serial reduction to NO in regulation of gastric function. Intriguingly, the nitrite that survives gastric passage is absorbed and can later recycle to NO in blood and tissues via several enzymatic as well as non-enzymatic pathways. Such systemic NO generation is likely involved in regulation of cardiovascular function and tissue homeostasis, especially in response to ischemia and hypoxia.
The role of the intestinal microflora in the development and correct functionality of the immune system is becoming increasingly evident. A perturbation of the gastrointestinal microflora or unwanted immune responses to this flora have been demonstrated to play a critical role in the pathogenesis of inflammatory bowel disease (IBD) in experimental animal models but recently also in tumorigenesis. It has been proposed to modify the intestinal microflora via the administration of probiotics in IBD patients. In order to better understand how probiotics could be beneficial to the host, it is important to understand how bacteria are handled at mucosal surfaces and how dendritic cells and epithelial cells communicate with each other to `tolerate' the intestinal flora. This article is intended to summarize recent advances on the function of gut immune cells and on some of the features that have been documented on the immunophenotypic characteristics of some probiotic strains.
The growth of 9 strains isolated from probiotic products and 18 strains from human feces belonging to Bifidobacterium longum biotype longum on media containing glucose or one of three oligosaccharides (i.e. lactulose, fructooligosacchrides, raffinose) as the sole carbohydrate source was compared in pure cultures. The strains differed in their growth profiles when tested on different oligosaccharides. Almost all probiotic isolates showed markedly poor growth on the oligosaccharides, especially lactulose and raffinose, as compared to the fecal isolates. Subsequent PCR assays targeting several genes associated with oligosaccharide metabolism showed an apparent lack of the gene BL0275 in the probiotic isolates; BL0275 encodes endogalactanase that liberates galactotrisaccharides from galactans and galactooligosaccharides in the probiotic isolates. The evidence suggests that most, if not all, of the probiotic isolates of B. longum biotype longum have a poor ability to utilize oligosaccharides.