9 research outputs found
Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation
Purpose: Gut microbiota regulate intestinal function and health.
However, mounting evidence indicates that they can also influence the
immune and nervous systems and vice versa. This article reviews the
bidirectional relationship between the gut microbiota and the brain,
termed the microbiota-gut-brain (MGB) axis, and discusses how it
contributes to the pathogenesis of certain disorders that may involve
brain inflammation.
Methods: Articles were identified with a search of Medline (starting in
1980) by using the key words anxiety, attention-deficit hypersensitivity
disorder (ADHD), autism, cytokines, depression, gut,
hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system,
microbiota, nervous system, neurologic, neurotransmitters, neuroimmune
conditions, psychiatric, and stress.
Findings: Various afferent or efferent pathways are involved in the MGB
axis. Antibiotics, environmental and infectious agents, intestinal
neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and
essential metabolites all convey information to the central nervous
system about the intestinal state. Conversely, the hypothalamic
pituitary adrenal axis, the central nervous system regulatory areas of
satiety, and neuropeptides released from sensory nerve fibers affect the
gut microbiota composition directly or through nutrient availability.
Such interactions seem to influence the pathogenesis of a number of
disorders in which inflammation is implicated, such as mood disorder,
autism-spectrum disorders, attention-deficit hypersensitivity disorder,
multiple sclerosis, and obesity.
Implications: Recognition of the relationship between the MGB axis and
the neuroimmune systems provides a novel approach for better
understanding and management of these disorders. Appropriate preventive
measures early in life or corrective measures such as use of
psychobiotics, fecal microbiota transplantation, and flavonoids are
discussed. (C) 2015 Elsevier HS Journals, Inc. All rights reserved
Mast cells regulate wound healing in diabetes
Diabetic foot ulceration is a severe complication of diabetes that lacks effective treatment. Mast cells (MCs) contribute to wound healing, but their role in diabetes skin complications is poorly understood. Here we show that the number of degranulated MCs is increased in unwounded forearm and foot skin of patients with diabetes and in unwounded dorsal skin of diabetic mice (P < 0.05). Conversely, postwounding MC degranulation increases in nondiabetic mice, but not in diabetic mice. Pretreatment with the MC degranulation inhibitor disodium cromoglycate rescues diabetes-associated wound-healing impairment in mice and shifts macrophages to the regenerative M2 phenotype (P < 0.05). Nevertheless, nondiabetic and diabetic mice deficient in MCs have delayed wound healing compared with their wild-type (WT) controls, implying that some MC mediator is needed for proper healing. MCs are a major source of vascular endothelial growth factor (VEGF) in mouse skin, but the level of VEGF is reduced in diabetic mouse skin, and its release from human MCs is reduced in hyperglycemic conditions. Topical treatment with the MC trigger substance P does not affect wound healing in MC-deficient mice, but improves it in WT mice. In conclusion, the presence of nondegranulated MCs in unwounded skin is required for proper wound healing, and therapies inhibiting MC degranulation could improve wound healing in diabetes