Expression of galectin 9 mRNA in lactose maldigestion and children’s obesity

OBJECTIVES AND STUDY: To investigate the association of mRNA expression of galectin - 9 (Gal - 9) and lactose maldigestion in children’s obesity with different genotypes of the lactase gene (LCT).METHODS: The study involved 85 children with obesity (BMI>97th percentile) aged 6-18 years. The study defined genotypes of LCT (material for investigation - venous blood), included expression of Gal - 9 mRNA (material for investigation - buccal epithelium) by real-time polymerase chain reaction analysis, and utilized the study of lactose maldigestion by Hydrogen breath testing. The first group of observations was presented by 44 children with genotype C/C -13910, the second group consisted of 41 children with phenotypically identical genotypes C/T -13910 and T/T -13910, p>0.05.RESULTS: Lactose maldigestion in children with genotype C/C -13910 averaged 36.05±4.73 ppm, in children with genotypes C/T -13910 - 22.61±4.1 ppm (p<0.05) and with genotype T/T -13910 - was absent (p<0.05). The average expression level of Gal - 9 mRNA in children with genotype C/C -13910 was 564.6±35.8 relation units (RU) ∆mRNA Gal - 9/mRNA actin and was 61.02±15.8 RU ∆mRNA Gal - 9/mRNA actin, p<0.01 in children with genotypes C/T and T/T -13910. The lowest mean level of expression of Gal - 9 mRNA (42.47±13.4 RU ∆mRNA Gal - 9/mRNA actin) was recorded in the subgroup of children with genotype C/C -13910 and lactose maldigestion (n=22). Whereas the largest mean level of expression of Gal - 9 mRNA was recorded in the subgroup of children with the C/C -13910 and without lactose maldigestion (n=22) - 1086.73±51.2 relation units ∆mRNA Gal - 9/mRNA actin, p<0.01.CONCLUSION: The expression level of Gal - 9 mRNA depends on lactose maldigestion in children with genotype C/C -13910

Assessment of lactase activity in humans by measurement of galactitol and galactonate in serum and urine after milk intake

ABSTRACT Background Lactase is an enzyme that hydrolyzes lactose into glucose and galactose in the small intestine, where they are absorbed. Hypolactasia is a common condition, primarily caused by genetic programming, that leads to lactose maldigestion and, in certain cases, lactose intolerance. Galactitol and galactonate are 2 products of hepatic galactose metabolism that are candidate markers for the intake of lactose-containing foods. Objectives The primary objective of the study was to explore the changes in serum and urine metabolomes during postprandial dairy product tests through the association between lactase persistence genotype and the postprandial dynamics of lactose-derived metabolites. Methods We characterized the 6-h postprandial serum kinetics and urinary excretion of lactose, galactose, galactitol, and galactonate in 14 healthy men who had consumed a single dose of acidified milk (800 g) which contained 38.8 g lactose. Genotyping of LCT-13910 C/T (rs4988235) was performed to assess primary lactase persistence. Results There were 2 distinct postprandial responses, classified as high and low metabolite responses, observed for galactose, and its metabolites galactitol and galactonate, in serum and urine. In all but 1 subject, there was a concordance between the high metabolite responses and genetic lactase persistence and between the low metabolite responses and genetic lactase nonpersistence (accuracy 0.92), galactitol and galactonate being more discriminative than galactose. Conclusions Postprandial galactitol and galactonate after lactose overload appear to be good proxies for genetically determined lactase activity. The development of a noninvasive lactose digestion test based on the measurement of these metabolites in urine could be clinically useful. This trial was registered at clinicaltrials.gov as NCT02230345.

TREATMENT OF LACTASE DEFICIENCY IN CHILDREN’S OBESITY WITH GENOTYPE C/C 13910 OF LACTASE GENE

Introduction: Excess lactose in the diet of modern man causes the development of not only lactase deficiency, but it can be a factor that contributes to obesity. The aim: To study associations between obesity and genotype C/C 13910 of lactase gene (LCT) in children, to investigate the effectiveness of treatment using drug exogenous lactase and a low-lactose diet. Materials and methods: genotyping of lactase gene by real-time polymerase chain reaction, determining the level of lactose maldigestion by hydrogen breath test (HBT), estimating the insulin resistance with the HOMA-IR index in 70 obese children and 40 healthy children 6 - 18 years. Obese children with genotype C/C 13910 and lactose maldigestion (n=40) were randomized in two groups: children from group I (n=20) received an exogenous lactase preparation, and children from group II (n=20) - low-lactose diet. Results: in obese children, the genotype C/C 13910 is 2 times more often than in healthy children. Obese children with genotype C/C 13910 have a significantly higher value of HBT (32.8–39.8 ppm) compared to healthy children (p<0.05), and an increased value of the HOMA-IR index. After treatment, there was a significant decrease in HBT and the HOMA-IR index in the two comparison groups. Conclusions: signs of insulin resistance are observed in children with obesity, genotype C/C 13910 and lactose maldigestion. The use of exogenous lactase in the therapy or the administration of a low-lactose diet cause approximately the same decrease in the HOMA-IR index.

Lactose Intolerance, Dairy Avoidance, and Treatment Options

Lactose intolerance refers to symptoms related to the consumption of lactose-containing dairy foods, which are the most common source for this disaccharide. While four causes are described, the most common is the genetically-determined adult onset lactose maldigestion due to loss of intestinal lactase governed by control of the gene by a 14,000 kb promoter region on chromosome 2. Gastrointestinal symptoms from lactose have expanded to include systemic effects and have also been confounded by other food intolerances or functional gastrointestinal disorders. Partly because lactose maldigestion is often interpreted as lactose intolerance (symptoms), focus of therapy for these symptoms starts with lactose restriction. However, withholding of dairy foods completely is not appropriate due to a more favorable impact on health. Industrial efforts to substitute with plant-based products is not completely successful at this time. This narrative article reviews the complexities of the perception of lactose intolerance, its epidemiology, and pathogenesis. Treatments are discussed, including the inappropriateness of dairy avoidance. In conjunction, effects of dairy products on 19 common diseases are reviewed. Different methods of treatment, lactose-reduced products, plant-based dairy substitutes, adaptation, prebiotics, exogenous lactase, probiotics, and some other dietary interventions are further discussed.

Carbohydrate intolerance

Symptoms such as watery diarrhoea, wind, and abdominal cramps should raise the possibility of carbohydrate intolerance. Lactose maldigestion is the most common cause and can be transient, after gastroenteritis, or in some populations is genetically determined with increasing age. Congenital sucrase–isomaltase deficiency (CSID) is underdiagnosed but amenable to treatment with dietary modification and oral enzyme replacement. Glucose–galactose malabsorption presents with watery diarrhoea from the time of first feeds. Investigations include sugar chromatography (when available), breath hydrogen testing, mucosal enzyme assay, and gene testing for CSID.

Adult Lactose Digestion Status and Effects on Disease

BACKGROUND: Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes.OBJECTIVES: To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions.METHODS: A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic.RESULTS: The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide.DISCUSSION: The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases.CONCLUSIONS: Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.