[Genetically determined trehalase deficiency in various population groups of Russia and neighboring countries].

Due to the low specificity and sensitivity of non-invasive clinical tests trehalose malabsorption remained out of sight of gastroenterologists. Therefore, the specialists regard this disorder as rare. Trehalose became widely used in the food industry as a harmless sucrose substitute, sweetener and stabilizer. After the discovery of the trehalase gene (rs2276064 TREH), it was found that the A*TREH allele is the determinant of the disaccharide absorption disorders, and the allele's carriership may be high in some groups. There is not enough information on the A*TREH frequency in the population of Russia. The aim of the study was to analyze the allele and genotype frequencies of the trehalase gene (rs2276064 TREH) in the main population groups of the Russian Federation and neighboring countries. Methods. DNA samples from 1146 unrelated subjects belonging to 21 population groups of Russia, Azerbaijan, Tajikistan and Mongolia were genotyped by the two following methods: 1) using the Infinium iSelect HD Custom Genotyping BeadChip (Illumina, USA) on the iScan platform; 2) by the real time polymer-chain reaction (PCR) method on the Bio-Rad CFX96 Touch amplifier. Results. It has been found that on the territory of the Russian Federation the frequency of the A*TREH allele increases from the west to the east. The frequencies are lowest in the groups of Russians and Finns of the Northwest (0.01-0.03), up to 0.07 in the populations of Central Russia and the Volga region, and even higher toward the Southern Urals (Bashkirs 0.15), in the Transurals and Southern Siberia (0.19 in the Altai people, 0.30 in the Tuvinians and Mongols). Up to 1% of the population of the European part of the Russian Federation have the AA*TREH genotype (i.e. trehalose intolerance in phenotype), and up to 15% (GA*TREH genotype) have a reduced ability to absorb the disaccharide. In the Asian part of the country (Siberia, Altai, Baikal) the genotypes carriers constitute up to 12 and 46% respectively. Conclusion. Trehalose malabsorbtion is an underappreciated problem of particular practical importance for regions with high concentrations of indigenous population (Yakutia-Sakha, Buryatia, Tyva, etc.). It would be feasible to consider food labelling of trehalose.

Trehalose accumulation enhances tolerance of Saccharomyces cerevisiae to acetic acid.

Trehalose confers protection against various environmental stresses on yeast cells. In this study, trehalase gene deletion mutants that accumulate trehalose at high levels showed significant stress tolerance to acetic acid. The enhancement of trehalose accumulation can thus be considered a target in the breeding of acetic acid-tolerant yeast strains.

Deciphering the roles of trehalose and Hsp104 in the inhibition of aggregation of mutant huntingtin in a yeast model of Huntington's disease.

Despite the significant amount of experimental data available on trehalose, the molecular mechanism responsible for its intracellular stabilising properties has not emerged yet. The repair of cellular homeostasis in many protein-misfolding diseases by trehalose is credited to the disaccharide being an inducer of autophagy, a mechanism by which aggregates of misfolded proteins are cleared by the cell. In this work, we expressed the pathogenic N-terminal fragment of huntingtin in Δnth1 mutant (unable to degrade trehalose) of Saccharomyces cerevisiae BY4742 strain. We show that the presence of trehalose resulted in the partitioning of the mutant huntingtin in the soluble fraction of the cell. This led to reduced oxidative stress and improved cell survival. The beneficial effect was independent of the expression of the major cellular antioxidant enzyme, superoxide dismutase. Additionally, trehalose led to the overexpression of the heat shock protein, Hsp104p, in mutant huntingtin-expressing cells, and resulted in rescue of the endocytotic defect in the yeast cell. We propose that at least in the initial stages of aggregation, trehalose functions as a stabiliser, increasing the level of monomeric mutant huntingtin protein, with its concomitant beneficial effects, in addition to its role as an inducer of autophagy.

Fructose, trehalose and sorbitol malabsorption.

Carbohydrate malabsorption is a frequent clinical condition, often associated with abdominal symptoms. Although lactose represents the most commonly malabsorbed sugar, also other carbohydrates, such as fructose, trehalose and sorbitol may be incorrectly absorbed in the small intestine. Fructose malabsorption seems more common in patients with functional bowel disease, even if randomized and controlled studies on these topic were few and on small samples. Interpretation of breath hydrogen testing is difficult. In particular, neither studies comparing this test with a gold standard, nor validated doses and concentrations to be used, are available. Trehalose malabsorption due to trehalase deficiency represents a very rare condition and available studies do not support its relevance in clinical practice. Sorbitol absorption is dose and concentration related, and depends on the entity of intestinal absorption surface. Nevertheless, the finding of its malabsorption is not expression of a specific cause of intestinal bowel damage. From available data, it is not possible to draw definite conclusions about clinical relevance of fructose, trehalose and sorbitol malabsorption, as well as, about diagnostic accuracy of commonly used tests to detect all these conditions. On the other hand, in patients who refer abdominal discomfort after ingestion of different carbohydrate-containing foods, a small intestinal bacterial overgrowth, should be promptly considered. This is because the large amount of intestinal bacteria may unspecifically ferment sugars, causing an abnormal H2 production and consequently a misleading diagnosis of sugar malabsorption.

Intestinal trehalase activity in a UK population: establishing a normal range and the effect of disease.

Trehalose is a disaccharide, the main dietary source being mushrooms. It has been approved as an additive in the preparation of dried food. Isolated intestinal trehalase deficiency is found in 8% of Greenlanders, but is rare elsewhere. The normal range of trehalase activity and the incidence of isolated trehalase deficiency in the UK have not been reported. Patients (n 400) were investigated for suspected malabsorption. Endoscopic distal duodenal biopsies were taken for histological assessment and maltase, sucrase, lactase and trehalase estimation. Disaccharidase activities were determined by Dahlqvist's technique (Dahlqvist, 1968). Most patients (n 369) had normal duodenal histology. In these, square root transformation of trehalase activity produced a normal distribution. The normal range (mean +/- 2 SD) was 4.79-37.12 U/g protein. One patient had an isolated borderline trehalase deficiency. The thirty-one patients with villous atrophy had significantly reduced disaccharidase activities. With ingestion of a gluten-free diet, maltase, sucrase and trehalase activities recovered to normal in most patients, whereas lactase activity did not. The normal range and very low incidence of isolated enzyme deficiency is comparable with that described in populations from the USA and mainland Europe. Activity is significantly reduced in untreated coeliac disease and recovers with treatment with a gluten-free diet. There is no place for routine determination of trehalase activity in the UK population and there should be no concern over the introduction of trehalose-containing dried foods.

Low trehalase activity is associated with abdominal symptoms caused by edible mushrooms.

BACKGROUND: The purpose of the study was to evaluate whether maldigestion of trehalose causes abdominal symptoms and which available diagnostic method best distinguishes intolerant from tolerant subjects. METHODS: A 25-g oral trehalose load test was performed in 64 subjects. The 19 experiencing clear symptoms constituted the trehalose-intolerant subjects. Changes from base-line levels of blood glucose, breath hydrogen, and methane and symptoms were recorded after the test. Trehalase activity was determined in serum and on a duodenal biopsy specimen obtained by endoscopy. RESULTS: Intolerant subjects were best differentiated from tolerant subjects by changes in breath gases (hydrogen and methane) and duodenal trehalase to sucrase ratio. The change in breath gases correlated inversely with duodenal trehalase activity, duodenal trehalase to sucrase ratio, and plasma trehalase activity. The correlation between serum and duodenal trehalase activities was on the order of 0.6. Two subjects were found to have trehalase deficiency. CONCLUSIONS: It is obvious that trehalose maldigestion can cause symptoms similar to those of lactose maldigestion and intolerance. Three factors control the genesis of symptoms: 1) the activity of small-bowel trehalase: if it is low, trehalose is maldigested and more trehalose is passed into the colon; 2) the maldigested trehalose, which causes osmotic water flow into the colon, resulting in loose stools and diarrhea; and 3) most importantly, the microflora of the colon, from which symptoms will arise if there are bacteria capable of producing gases from maldigested trehalose. If colonic bacteria cannot produce gases, then distention of the abdomen and intestinal gas expulsion as eructations and flatus will not occur.

Trehalase deficiency in Greenland.

Small-intestinal surgical biopsy specimens from 97 adult Greenlanders showed an incidence of trehalase deficiency in at least 8%. Trehalose tolerance tests performed in three individuals with low trehalase activity (6 IU/g protein) showed no increase in the blood glucose concentration. Three trehalase-deficient patients had lactase deficiency too. Trehalase deficiency is not considered to have any significance from a nutritional point of view.

Trehalase deficiency. Prevalence and relation to single-cell protein food.

Perspectives in nutrition suggest a greater use of single-cell proteins in the future. The problems of a high purine content and of potential allergens have been solved by technology. The single-cell proteins may contain trehalose, the absorption of which by the human intestine necessitates prior hydrolysis by trehalase, a specific brush-border disaccharidase. The enzymatic analysis of 100 intestinal biopsies discovered 2 cases of very low trehalase level, with an expected clinical intolerance to even small doses of trehalose. It is concluded that tolerance to high doses of trehalose should be excellent in about 98% of healthy people.