Immunology of pre- and probiotic supplementation.

The notion that ingestion of so-called ‘good’ bacteria (‘probiotics’) or food components favouring growth of probiotic bacteria (‘prebiotics’) can have advantageous effects on human health arouses strong opinions, both in agreement and against. Remarkably few data have been fuelling this debate. Nevertheless, two important studies have now appeared, one published in The Lancet showing that probiotic supplementation in patients with acute pancreatitis is deleterious and one in this issue of the British Journal of Nutrition by Arribas et al. , showing the beneficial effects of Lactobacillus fermentum in an experimental model of septic shock. Together with existing studies on the immunological effects of preand probiotic food supplementation, the main effects of such treatment seems localised to inducing anergy in the T cell compartment. Health claims of preand probiotic treatment should be interpreted within this framework. The mucosal surface of the intestine represents the major contact of the body with microbiological stimuli and in this compartment is most of the immunological activity of the body. Despite the bewildering number of bacteria in the intestine, especially the colon, in most cases the human immune system acts to tolerate harmless bacteria while eliminating pathogenic bacteria. A variety of immunological mechanisms, which include the existence of an efficient colonic columnic epithelial barrier, the production of antibacterial peptides (for example, the production of a-defensins by the Paneth cells), constant sentinel-like surveillance by CD16 monocytes and efficient recruitment of granulocytes to areas in which barrier integrity has been compromised mediates protection of the body against the microbiological onslaught on the mucosal surface. Counterintuitively, reduced activity of these innate mechanisms, as a consequence of genetic defects, seems responsible for chronic intestinal inflammation in Crohn’s disease, which is associated with an abnormally exaggerated mucosal immune response to an otherwise normal intestinal flora. The sheer size of the mucosal immune system as compared with other parts of the immune system makes the notion that influencing the mucosal immune system by dietary means plausible. It usually assumed that the flora along the intestinal tract is established early in life and in mammalian organisms resembles the flora of the mother and is stable. Nevertheless, preor probiotic treatment seems capable of at least temporally altering this composition. Probiotics are a group of bacteria of which theLactobacilli and Bifidobacteria are the most prominent members and it is claimed that they have anti-inflammatory properties. Accordingly, such probiotic bacterial strains protect against experimental colitis in rodents – 7) as well as exacerbations of inflammatory bowel disease and topical allergy in human patients. In agreement, food supplements specifically enhancing the growth of probiotic bacteria are recognised to be beneficial in a variety of inflammatory conditions including inflammatory bowel disease and genetically engineering plants for the production of prebiotics has become an industry in its own right despite limited insight into the immunological mechanisms induced by such food supplementation. In contrast to most micro-organisms, some probiotic bacteria are capable of impairing the immunological reaction to their mucosal presence in particular and have a dampening effect on the adaptive immune system in general. To a certain extent probiotics exert their action by niche occupation and thus preventing colonisation of the bowel by pathogenic bacterial species – . Moreover, it has become clear that probiotic bacteria directly influence host physiology, especially barrier function, but their anti-inflammatory effects in inflammatory bowel disease and topical allergic disease suggest that a direct effect on the immune system is involved as well. As inflammatory bowel disease displays mainly Th1 characteristics and topical allergies are characterised by a Th2 phenotype and both benefit from probiotic supplementation, the immunological effects of probiotic bacteria probably do not involve altered Th1/ Th2 polarisation. There is evidence from a double-blind placebo-controlled study that Lactobacillus reuteri protectis reduces short-term sick-leave from work caused by respiratory or gastrointestinal infections – . This effect is also not easily explained via an influence on altered Th1/Th2 polarisation but suggests effects of probiotic treatment at a more fundamental level of human immunobiology. The study of Arribas et al. , which documents a preventive effect of Lactobacillus fermentum in a murine model of septic shock, provides important clues as to what these mechanisms might be. The authors document markedly reduced splenic T cell responses, suggesting that the T cell compartment might be the relevant target for many of the effects observed by probiotics. Also, the earlier observation reported by the same laboratory that different probiotic bacteria, as well as prebiotics, are beneficial in a trinitrobenzenesulfonic acid model of rat colitis (which represents a classical T cellmediated inflammation) points in this direction. Interestingly, both in vitro as well as in human volunteers or patients with Crohn’s disease, Lactobacillus rhamnosus induced an anergy-like T cell hyporesponsiveness which was apparently mediated via reduced co-stimulatory activity in dendritic cells, which fits well with a scheme that preand probiotics act through diminished T cell activation. This hypothesis also proves exceedingly useful in explaining the clinical British Journal of Nutrition (2009), 101, 2–4 doi:10.1017/S0007114508020746 q The Authors 2008