The gut microbiome and the brain.

The human gut microbiome impacts human brain health in numerous ways: (1) Structural bacterial components such as lipopolysaccharides provide low-grade tonic stimulation of the innate immune system. Excessive stimulation due to bacterial dysbiosis, small intestinal bacterial overgrowth, or increased intestinal permeability may produce systemic and/or central nervous system inflammation. (2) Bacterial proteins may cross-react with human antigens to stimulate dysfunctional responses of the adaptive immune system. (3) Bacterial enzymes may produce neurotoxic metabolites such as D-lactic acid and ammonia. Even beneficial metabolites such as short-chain fatty acids may exert neurotoxicity. (4) Gut microbes can produce hormones and neurotransmitters that are identical to those produced by humans. Bacterial receptors for these hormones influence microbial growth and virulence. (5) Gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve. Through these varied mechanisms, gut microbes shape the architecture of sleep and stress reactivity of the hypothalamic-pituitary-adrenal axis. They influence memory, mood, and cognition and are clinically and therapeutically relevant to a range of disorders, including alcoholism, chronic fatigue syndrome, fibromyalgia, and restless legs syndrome. Their role in multiple sclerosis and the neurologic manifestations of celiac disease is being studied. Nutritional tools for altering the gut microbiome therapeutically include changes in diet, probiotics, and prebiotics.

Mechanisms of behavioral, atopic, and other reactions to artificial food colors in children.

This review examines the research on mechanisms by which artificial food colors (AFCs) and common foods may cause behavioral changes in children with and without attention-deficit/hyperactivity disorder (ADHD). Children with ADHD show excess inattention, impulsivity, and hyperactivity. Studies have shown that a subgroup of children (with or without ADHD) react adversely to challenges with AFCs. Many early studies found few children who reacted to challenges with 20-40 mg of AFCs. However, studies using at least 50 mg of AFCs showed a greater percentage of children who reacted to the challenge. Three types of potential mechanisms are explored: toxicological, antinutritional, and hypersensitivity. Suggestions for future studies in animals and/or children include dose studies as well as studies to determine the effects of AFCs on the immune system, the intestinal mucosa, and nutrient absorption. Given the potential negative behavioral effects of AFCs, it is important to determine why some children may be more sensitive to AFCs than others and to identify the tolerable upper limits of exposure for children in general and for children at high risk.

Diet and inflammation.

The emerging role of chronic inflammation in the major degenerative diseases of modern society has stimulated research into the influence of nutrition and dietary patterns on inflammatory indices. Most human studies have correlated analyses of habitual dietary intake as determined by a food frequency questionnaire or 24-hour recall with systemic markers of inflammation like high-sensitivity C-reactive protein (HS-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). An occasional study also includes nutrition analysis of blood components. There have been several controlled interventions which evaluated the effect of a change in dietary pattern or of single foods on inflammatory markers in defined populations. Most studies reveal a modest effect of dietary composition on some inflammatory markers in free-living adults, although different markers do not vary in unison. Significant dietary influences have been established for glycemic index (GI) and load (GL), fiber, fatty acid composition, magnesium, carotenoids, and flavonoids. A traditional Mediterranean dietary pattern, which typically has a high ratio of monounsaturated (MUFA) to saturated (SFA) fats and ω-3 to ω-6 polyunsaturated fatty acid (PUFAs) and supplies an abundance of fruits, vegetables, legumes, and grains, has shown anti-inflammatory effects when compared with typical North American and Northern European dietary patterns in most observational and interventional studies and may become the diet of choice for diminishing chronic inflammation in clinical practice.

Patient-centered care: antecedents, triggers, and mediators.

Functional medicine is essentially patient centered, rather than disease centered. A structure is presented for uniting a patient-centered approach to diagnosis and treatment with the fruits of modern clinical science (which evolved primarily to serve the prevailing model of disease-centered care). The core scientific concepts of disease pathogenesis are antecedents, triggers, and mediators. Antecedents are factors, genetic or acquired, that predispose to illness; triggers are factors that provoke the symptoms and signs of illness; and mediators are factors, biochemical or psychosocial, that contribute to pathological changes and dysfunctional responses. Understanding the antecedents, triggers, and mediators that underlie illness or dysfunction in each patient permits therapy to be targeted to the needs of the individual. The conventional diagnosis assigned to the patient may be of value in identifying plausible antecedents, triggers or mediators for each patient, but is not adequate by itself for the designing of patient-centered care. Applying the model of person-centered diagnosis to patients facilitates the recognition of disturbances that are common in people with chronic illness. Diet, nutrition, and exposure to environmental toxins play central roles in functional medicine because they may predispose to illness, provoke symptoms, and modulate the activity of biochemical mediators through a complex and diverse set of mechanisms. Explaining those mechanisms is a key objective of the Textbook of Functional Medicine (from which this article is excerpted). A patient's beliefs about health and illness are critically important for self-care and may influence both behavioral and physiological responses to illness. Perceived self-efficacy is an important mediator of health and healing. Enhancement of patients' self-efficacy through information, education, and the development of a collaborative relationship between patient and healer is a cardinal goal in all clinical encounters.