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The health-promoting effects of lactic acid bacteria (LAB) are well recognised, making them a popular functional food ingredient. Commercially available probiotic products are often promoted as capable of improving immune defences also in healthy subjects. However, while strain-specific differences exist in the effects of LAB, conventional yoghurt bacteria have proved beneficial as well. For comparing the immunological effects of conventional and probiotic LAB, young healthy women received either a commercially available probiotic fermented milk product or a conventional yoghurt for four weeks. Both treatments showed comparable effects resulting in a stronger immunological reaction to stimuli (natural cytotoxicity against cancer cells, mitogen-induced T-lymphocyte activation and stimulated cytokine production). To study the mechanisms behind these effects, conventional (Lactobacillus delbrueckii) and probiotic (Lactobacillus rhamnosus GG), LAB were compared in vitro at the cellular level. Interestingly, L. rhamnosus GG was more potent in inducing maturation of dendritic cells (DC) that play a substantial role in directing the immune response to stimuli. In turn, L. delbrueckii provoked a higher secretion of proinflammatory cytokines as well as IL-10. These effects were, however, observed only after direct incubation of DC and LAB, not when both were separated by a layer of enterocyte-like Caco-2 cells. LAB also induced cytokine secretion in peripheral blood mononuclear cells in a similar manner and this effect was reduced in a Caco-2 cell model, suggesting a modulating influence of gut epithelial cells. While both conventional and probiotic strains modulate the immune response, specific properties may offer therapeutic options in the treatment of certain diseases.
Session 8: Probiotics in the defence and metabolic balance of the organism
Lactic acid bacteria are present in many foods such as yoghurt and are frequently used as probiotics to improve some biological functions of the host. Many researchers have evaluated the effects of yoghurt and lactic acid bacteria against diseases such as cancer and intestinal inflammation. The preventive effect of probiotics on intestinal carcinogenesis may be associated with changes in the intestinal microbiota, suppressing the growth of bacteria that convert procarcinogens into carcinogens. Other mechanisms could be related to the immune response modulation and have been evaluated using milks fermented with lactic acid bacteria in chemically induced colon cancer and hormone-dependent breast cancer models. We demonstrated, using a murine colon cancer model, that yoghurt consumption inhibited tumour growth by decreasing the inflammatory response by increasing IL-10-secreting cells, cellular apoptosis and diminishing procarcinogenic enzymes. Milk fermented with Lactobacillus helveticus R389 delayed breast tumour growth by decreasing IL-6 and increasing IL-10 in serum and in the mammary glands and tumour-infiltrating immune cells. Previous results obtained with yoghurt administration in a colon cancer model led us to analyse its effect on a trinitrobenzenesulfonic acid-induced intestinal inflammation model in mice. Yoghurt was able to attenuate the symptoms of acute inflammation by reducing inflammatory cytokines, and increasing regulatory cytokine IL-10-producing cells, leading to desirable changes of the intestinal microbiota. It was demonstrated, by using murine models, that the consumption of fermented milks can modulate the immune system and can maintain it in a state of surveillance, which could affront different pathologies such as cancer and intestinal inflammation.
Probiotics, defined as living micro-organisms that provide a health benefit to the host when ingested in adequate amounts, have been used traditionally as food components to help the body to recover from diarrhoea. They are commonly ingested as part of fermented foods, mostly in fresh fermented dairy products. They can interact with the host through different components of the gut defence systems. There is mounting clinical evidence that some probiotics, but not all, help the defence of the host as demonstrated by either a shorter duration of infections or a decrease in the host's susceptibility to pathogens. Different components of the gut barrier can be involved in the strengthening of the body's defences: the gut microbiota, the gut epithelial barrier and the immune system. Many studies have been conducted in normal free-living subjects or in subjects during common infections like the common cold and show that some probiotic-containing foods can improve the functioning of or strengthen the body's defence. Specific probiotic foods can be included in the usual balanced diet of consumers to help them to better cope with the daily challenges of their environment.
Obesity is a major public health issue as it is causally related to several chronic disorders, including type-2 diabetes, CVD and cancer. Novel research shows that the gut microbiota is involved in obesity and metabolic disorders, revealing that obese animal and human subjects have alterations in the composition of the gut microbiota compared to their lean counterparts. Moreover, transplantation of the microbiota of either obese or lean mice influences body weight in the germ-free recipient mice, suggesting that the gut ecosystem is a relevant target for weight management. Indigenous gut microbes may regulate body weight by influencing the host's metabolic, neuroendocrine and immune functions. The intestinal microbiota, as a whole, provides additional metabolic functions and regulates the host's gene expression, improving the ability to extract and store energy from the diet and contributing to body-weight gain. Imbalances in the gut microbiota and increases in plasma lipopolysaccharide may also act as inflammatory factors related to the development of atherosclerosis, insulin resistance and body-weight gain. In contrast, specific probiotics, prebiotics and related metabolites might exert beneficial effects on lipid and glucose metabolism, the production of satiety peptides and the inflammatory tone related to obesity and associated metabolic disorders. This knowledge is contributing to our understanding of how environmental factors influence obesity and associated diseases, providing new opportunities to design improved dietary intervention strategies to manage these disorders.
Probiotics are bacteria, but sometimes fungi, which when taken by the oral route may give some health benefits. The most compelling evidence for beneficial effects of probiotics is in the prevention and reduction in the duration of symptoms related to gut infectious disease. There is also evidence to show that some specific probiotics are beneficial in Clostridium difficile diarrhoea in the elderly. As further and better controlled clinical studies have appeared, some specific probiotics also appear to have beneficial effects in perhaps preventing and reducing the duration of symptoms due to acquired upper respiratory tract infections. In an attempt to explain these effects, attention has turned to the effects of some specific probiotics on the immune system. There is evidence that some specific probiotics can alter monocyte and natural killer cell function in the blood. Evidence is also accumulating that taking some specific probiotics can boost antibody responses to oral and systemically administered vaccines. The effect when shown is modest and is not always seen in different studies to all vaccines, but there is enough of a trend to make the area worthy of further investigation, particularly to tease out the mechanisms involved.
Session 9: Food ingredients, immunity and inflammation: animal and in vitro models
The epithelial barrier of the intestine and the gut-associated lymphoid tissue (GALT) protects the host against luminal pathogenic micro-organisms. This is important at weaning, when animals are exposed to infectious agents and stresses. We have developed a rat model of intestinal inflammation post weaning, based on the systemic administration of Staphylococcus aureus enterotoxin B (SEB). Since the inflammatory response obtained is mild, the food intake pattern is not affected, which makes this model useful for studies of nutritional therapies for intestinal inflammatory disease. SEB increased T-lymphocytes in Peyer's patches and the number of activated T-lymphocytes in mesenteric lymph nodes (organized GALT). In the lamina propria, SEB increased activated T-lymphocytes as well as cytotoxic and natural killer-cell populations of the diffuse GALT. It also increased pro-inflammatory cytokines and inflammatory mediators in both Peyer's patches and mucosa. Rats given SEB had higher paracellular permeability to macromolecules, which was associated with a reduction in epithelial tightness. This model was used to examine whether dietary supplementation with spray-dried animal plasma proteins affects intestinal inflammation. Results showed that dietary plasma proteins can attenuate the mucosal immune response in both organized and diffuse GALT and that these effects are mediated by a reduction in the production of pro-inflammatory cytokines.
Bioactive peptides have proven to be active in several conditions, including inflammatory bowel disease (IBD). This is a chronic and relapsing condition of unknown aetiology that comprises chiefly ulcerative colitis and Crohn's disease. Although there are treatments for IBD, they have frequent side effects and they are not always effective; therefore there is a need for new therapies that could alleviate this condition. Two bioactive peptides present in milk (transforming growth factor-β (TGF-β) and casein macropeptide, also named glycomacropeptide) have been shown to have intestinal anti-inflammatory activities. In fact, TGF-β is currently added to formulas intended for patients with IBD, and several studies indicate that these formulas could induce clinical remission. In this paper, evidence supporting the anti-inflammatory effect of TGF-β and bovine glycomacropeptide, as well as their mechanisms of action, is reviewed, focusing on the evidence obtained in animal models.