The Barker hypothesis

The Barker hypothesis proposed that adverse nutrition in early life, including prenatally as measured by birth weight, increased susceptibility to the metabolic syndrome which includes obesity, diabetes, insulin insensitivity, hypertension, and hyperlipidemia and complications that include coronary heart disease and stroke. Periods of rapid postnatal growth associated with high-energy intake seem to be risk factors, along with a high-energy western diet. Theories proposing the mechanism of this association include the thrifty gene, bet-hedging, fetal predictive adaptive response, and drifty phenotype hypotheses. The cause of metabolic syndrome is likely to be multifactorial, with many nuclear DNA and cellular RNA sequences acting in concert with environmental influences. Epidemiological data in humans and experimental data indicate that transgenerational epigenetic inheritance is a possible mechanism where a history of starvation or deprivation during early life is seen in a grandparent and transgenerational effects are seen in their grandchildren. It remains to be seen whether this is mediated by heritable RNA sequences, or by acquired, possibly mosaic mutations in DNA coding for example for regulatory RNAs. Recent research has raised the possibility that the nature and quantity of gastrointestinal microorganisms (microbiota) can be modified by diet and conversely can modify an animal's metabolic program. As the microbiota is inherited largely from the mother, modification of her nutrition, health before and during pregnancy, and mode of delivery could influence the child's microbiota, introducing further potential avenues to improve the prevention, reduction of complications, and treatment of malnutrition and metabolic syndrome

Autoimmune atrophic gastritis-pathogenesis, pathology and management.

Autoimmune gastritis is a chronic progressive inflammatory condition that results in the replacement of the parietal cell mass by atrophic and metaplastic mucosa. A complex interaction of autoantibodies against the parietal cell proton pump and sensitized T cells progressively destroy the parietal cells, inducing hypochlorhydria and then achlorhydria, while autoantibodies against the intrinsic factor impair the absorption of vitamin B12. The resulting cobalamin deficiency manifests with megaloblastic anaemia and neurological and systemic signs and symptoms collectively known as pernicious anaemia. Previously believed to be predominantly a disease of elderly women of Northern European ancestry, autoimmune gastritis has now been recognized in all populations and ethnic groups, but because of the complexity of the diagnosis no reliable prevalence data are available. For similar reasons, as well as the frequent and often unknown overlap with Helicobacter pylori infection, the risk of gastric cancer has not been adequately assessed in these patients. This Review summarizes the epidemiology, pathogenesis and pathological aspects of autoimmune metaplastic atrophic gastritis. We also provide practical advice for the diagnosis and management of patients with this disease