The microbiota of the human large intestine influences health and well-being. Whereas it has long been accepted that gut bacteria play a role in host pathogenesis, current opinion is that certain microflora components can have beneficial effects on gastroenteritis resistance, blood lipids, antitumor properties, lactose tolerance, and gastrointestinal immunity. It is postulated that in the infant gut an elevated bifidobacterial count may be associated with health advantages that breast-fed infants may have over formula-fed infants. Whereas beneficial aspects of the human gut flora still need definitive confirmation and mechanistic explanations, there is now interest in modulating the composition of gut flora such that a potentially more remedial community exists. This may be achieved through the targeted use of dietary supplementation. This article provides an overview of how probiotics, prebiotics, and synbiotics may contribute toward nutritional modulation of the gut microecology, with emphasis on the neonatal intestine where appropriate. The use of modern molecular methods, as an essential step forward for assessing the validity and accuracy of the modulatory approach, is also discussed.
Human beings evolved consuming a diet that contained about equal amounts of n-3 and n-6 essential fatty acids. Over the past 100-150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from approximate to 20-30:1 instead of the traditional range of 1-2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 Fatty acids, however, have antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid, found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases.
The gastrointestinal tract of a normal fetus is sterile. During the birth process and rapidly thereafter, microbes from the mother and surrounding environment colonize the gastrointestinal tract of the infant until a dense, complex microbiota develops. The succession of microbes colonizing the intestinal tract is most marked in early development, during which the feeding mode shifts from breast-feeding to formula feeding to weaning to the introduction of solid food. Dynamic balances exist between the gastrointestinal microbiota, host physiology, and diet that directly influence the initial acquisition, developmental succession, and eventual stability of the gut ecosystem. In this review, the development of the intestinal microbiota is discussed in terms of initial acquisition and subsequent succession of bacteria in human infants. Intrinsic and extrinsic factors influencing succession and their health significance are discussed. The advantages of modern molecular ecology techniques that provide sensitive and specific, culture-independent evaluation of the gastroinrestinal ecosystem are introduced and discussed briefly. Further advances in our understanding of developmental microbial ecology in the neonatal gastrointestinal tract are dependent on the application of these modern molecular techniques.
Legumes play an important role in the traditional diets of many regions throughout the world. In contrast in Western countries beans tend to play only a minor dietary role despite the fact that they are low in fat and are excellent sources of protein, dietary fiber, and a variety of micronutrients and phytochemicals. Soybeans are unique among the legumes because they are a concentrated source of isoflavones. Isoflavones have weak estrogenic properties and the isoflavone genistein influences signal transduction. Soyfoods and isoflavones have received considerable attention for their potential role in preventing and treating cancer and osteoporosis. The low breast cancer mortality rates in Asian countries and the putative antiestrogenic effects of isoflavones have fueled speculation that soyfood intake reduces breast cancer risk. The available epidemiologic data are limited and only weakly supportive of this hypothesis, however, particularly for postmenopausal breast cancer. The data suggesting that soy or isoflavones may reduce the risk of prostate cancer are more encouraging. The weak estrogenic effects of isoflavones and the similarity in chemical structure between soybean isoflavones and the synthetic isoflavone ipriflavone, which was shown to increase bone mineral density in postmenopausal women, suggest that soy or isoflavones may reduce the risk of osteoporosis. Rodent studies tend to support this hypothesis, as do the Limited preliminary data from humans. Given the nutrient profile and phytochemical contribution of beans, nutritionists should make a concerted effort to encourage the public to consume more beans in general and more soyfoods in particular.
Herbs have been used as food and for medicinal purposes for centuries. Research interest has focused on various herbs that possess hypolipidemic, antiplatelet, antitumor, or immune-stimulating properties that may be useful adjuncts in helping reduce the risk of cardiovascular disease and cancer. In different herbs, a wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulfides, polyphenolics, carotenoids, coumarins, saponins, plant sterols, curcumins, and phthalides have been identified. Several of these phytochemicals either inhibit nitrosation or the formation of DNA adducts or stimulate the activity of protective enzymes such as the Phase II enzyme glutathione transferase (EC 220.127.116.11). Research has centered around the biochemical activity of the Allium sp. and the Labiatae, Umbelliferae, and Zingiberaceae families, as well as flaxseed, licorice root, and green tea. Many of these herbs contain potent antioxidant compounds that provide significant protection against chronic diseases. These compounds may protect LDL cholesterol from oxidation, inhibit cyclooxygenase and lipoxygenase enzymes, inhibit lipid peroxidation, or have antiviral or antitumor activity. The volatile essential oils of commonly used culinary herbs, spices, and herbal teas inhibit mevalonate synthesis and thereby suppress cholesterol synthesis and tumor growth.
Epidemiologic data support the association between high intake of vegetables and fruits and low risk of chronic disease. There are several biologically plausible reasons why consumption of vegetables and fruit might slow or prevent the onset of chronic diseases. Vegetables and fruit are rich sources of a variety of nutrients, including vitamins, trace minerals, and dietary fiber, and many other classes of biologically active compounds. These phytochemicals can have complementary and overlapping mechanisms of action, including modulation of detoxification enzymes, stimulation of the immune system, reduction of platelet aggregation, modulation of cholesterol synthesis and hormone metabolism, reduction of blood pressure, and antioxidant, antibacterial, and antiviral effects. Although these effects have been examined primarily in animal and cell-culture models, experimental dietary studies in humans have also shown the capacity of vegetables and fruit and their constituents to modulate some of these potential disease-preventive mechanisms. The human studies have relied on intermediate endpoints related to disease risk. Design methodologies used include multiple-arm trials, randomized crossover studies, and more compromised designs such as nonrandomized crossovers and pre- and posttreatment analyses. Length of treatment ranged from a single dose to years depending on the mechanism of interest. Stringency of dietary control varied from addition of supplements to a habitual diet to provision of all food for the duration of a treatment. Rigorously conducted experimental dietary studies in humans are an important link between population- and laboratory-based research.
We combined data from 5 prospective studies to compare the death rates from common diseases of vegetarians with those of nonvegetarians with similar lifestyles. A summary of these results was reported previously; we report here more details of the findings. Data for 76172 men and women were available. Vegetarians were those who did not eat any meat or fish (n = 27808). Death rate ratios at ages 16-89 y were calculated by Poisson regression and all results were adjusted for age, sex, and smoking status. A random-effects model was used to calculate pooled estimates of effect for all studies combined. There were 8330 deaths after a mean of 10.6 y of follow-up. Mortality from ischemic heart disease was 24% lower in vegetarians than in nonvegetarians (death rate ratio: 0.76; 95% CI: 0.62, 0.94; P 5 y. Further categorization of diets showed that, in comparison with regular meat eaters, mortality from ischemic heart disease was 20% lower in occasional meat eaters, 34% lower in people who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans. There were no significant differences between vegetarians and nonvegetarians in mortality from cerebrovascular disease, stomach cancer, colorectal cancer, lung cancer, breast cancer, prostate cancer, or all other causes combined.
The normal colonization of the mammalian intestine with commensal microbes is hypothesized to drive the development of the humoral and cellular mucosal immune systems during neonatal life and to maintain the physiologically normal steady state of inflammation in the gut throughout life. Neonatal conventionally reared mice and germ-free, deliberately colonized adult mice (gnotobiotic mice) were used to examine the efficacy of certain intestinal microbes.