Influencing factors on the severity of clinical and laboratory manifestations of carbohydrate malabsorption syndrome in early-aged children with rotavirus infection

Purpose — to determine the role of the lactase gene MCM6 allelic polymorphism 13910 C/T and the concomitant food allergy (FA) and atopic dermatitis (AD) on the formation of carbohydrate malabsorption syndrome manifestations in early-aged children with rotavirus infection (RVI). Materials and methods. 60 children aged 1–24 months with RVI were examined. The determination of single nucleotide polymorphism 13910 C/T of the MCM6 gene was performed by real-time polymerase chain reaction and the content of total Ig E in serum was determined by enzyme immunoassay for all children on the day of hospitalization. Total amount of carbohydrates in feces (Benedict's test) and the level of lactose in feces (Malfatti's test) were also determined in the dynamics of the disease (on the 3rd, 5th, 7th, 10th day). The analysis of the carbohydrate malabsorption syndrome clinical and laboratory signs was carried out in subgroups depending on the genotype 13910 C/T of the MCM6 gene and concomitant allergic pathology. Results. No significant differences were found in the maximum daily frequency of diarrhea, its duration and the frequency of intestinal colic and flatulence registration in children with genotypes C/C, C/T and T/T -13910 of the MCM6 gene (p>0.05). There was no statistically significant difference in the total level of carbohydrates and lactose in feces at all stages of the disease (p>0.05 on the 3rd, 5th, 7th, 10th). Children with concomitant FA and AD had 1.3 and 2 times higher daily frequency of liquid bowel movements during the height of the disease (p<0.05 on the 5th and 7th days, respectively), 1.3 times longer diarrhea (p<0.05), 1.6 and 1.8 times higher incidence of flatulence and intestinal colic (p<0.05). These children had 3 and 3.3 times higher Benedict's test values (p<0.01), as well as 3 and 2.5 times higher Malfatti's test values (p<0.01; p<0.05, respectively) on the 3rd and 5th days of RVI, respectively, than in patients without allergies, with a gradual decrease in this difference during the period of convalescence (p>0.05 on the 10th day). Conclusions. The allelic polymorphism 13910 C/T of the MCM6 gene does not affect the degree of oligosaccharide metabolism disorders in the intestines in early-aged children with RVI. Against the background of concomitant food allergy and atopic dermatitis in children with RVI, there are more pronounced laboratory signs of carbohydrate malabsorption, and, as a consequence, diarrhea more pronounced during the height of the disease with a higher incidence of flatulence and intestinal colic. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the author. Key words: rotavirus infection, early-aged children, carbohydrate malabsorption syndrome, lactase gene polymorphism, food allergy, atopic dermatitis.

Milk consumption and gastrointestinal symptoms in preschool girls with different lactase genotypes

AIM: To analyze the frequency of milk consumption and subjective symptoms of intolerance to dairy products in the population of three- to six-year-old girls (born and resident in Samara) based on the genotype of the lactase gene. MATERIALS AND METHODS: We included 103 preschool girls ranging three to six years of age. Parents were questioned about the frequency of milk consumption by the child (per week), as well as the presence of gastrointestinal symptoms in their children (abdominal pain, bloating, flatulence and diarrhea) and the suspected association of symptoms with milk consumption (according to the parents). Buccal samples were taken from all girls to determine the polymorphism of the lactase genes (determination of C/T-13910 variant of the MCM6 gene). RESULTS: A significant relationship between the frequency of milk consumption and the variant of the polymorphic locus of the lactase gene, MCM6 [C 13910T; which affects the expression of the lactase gene (LCT)] has not been established. There is no correlation in the enlarged gradation of frequent milk consumption (47 times a week) and rare milk consumption (23 times a week or less): of 53 girls with the CC genotype 27 (51%) often drink milk, 26 (49%) rarely drink milk; of 39 girls with CT genotype 23 (59%) often consume milk, 16 (41%) rarely consume milk; of 11 girls with the TT genotype, 8 (73%) often consume milk, 3 (27%) rarely consume milk (c2 1.94, p = 0.379). There was no significant relationship between the frequency of milk consumption, subjective symptoms of lactose intolerance (abdominal pain, bloating, flatulence and diarrhea) and the genotype; these symptoms were found only in four girls carrying the C allele (CC and CT genotypes) though not detected in girls with TT genotype. CONCLUSION: In girls of 36 years old, there is no relationship between the frequency of milk consumption, subjective symptoms of lactose intolerance and genotype of lactase gene.

Strain-level analysis of Bifidobacterium spp. from gut microbiomes of adults of differing lactase persistence genotypes

ABSTRACTOne of the strongest associations between human genetics and the gut microbiome is a greater relative abundance of Bifidobacterium in adults with lactase gene (LCT) SNPs associated with lactase-non persistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with varying lactase persistence genotypes. We further employed a novel genome-capture based enrichment of Bifidobacterium DNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times. B. adolescentis and B. longum were the most abundant Bifidobacterium species regardless of host LCT-genotype. LCT- genotypes could not be discriminated based on relative abundances of Bifidobacterium species or Bifidobacterium community structure. Metagenomic analysis of Bifidobacterium-enriched DNA revealed intra-individual temporal stability of B. longum, B. adolescentis, and B. bifidum strains against the background of a changeable microbiome. We also observed greater strain sharing within MZ twin pairs compared to unrelated individuals, and within GG compared to AA/AG individuals, but no effect of host LCTgenotype on Bifidobacterium strain composition. Our results support a “rising tide lift all boats” model for the dominant Bifidobacteria in the adult gut: their higher abundance in lactase-non persistent compared to lactase-persistent individuals results from an expansion at the genus level. Bifidobacterium species are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood.IMPORTANCEWhen human populations domesticated animals to drink their milk they adapted genetically with the ability to digest milk into adulthood (lactase persistence). The gut microbiomes of lactase non-persistent people (LNP) differ from those of lactase-persistent people (LP) by containing more bacteria belonging to the Bifidobacteria. These beneficial gut bacteria, which fall into many species, are known to degrade milk in the baby gut. Here, we asked if adult LP and LNP microbiomes differ in the species of Bifidobacteria present. We studied the gut microbiomes of LP and LNP adults, including twins, sampled at several times. In particular, we used a technique to selectively pull out the DNA belonging to the Bifidobacteria: analysis of these DNA segments allowed us to compare Bifidobacteria at the strain level. Our results show that the LNP enhance the abundance of Bifidobacteria regardless of species. We also noted that a person’s specific strains are recoverable several years later, and twins tend to share the same ones. Given that Bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long term, multi-generational inheritance.

Prospects of fermented milk products in children with primary hypolactasia of the adult type

Lactose (β-galactosyl-1,4 glucose) is milk sugar, the main disaccharide of human and other mammalian breast milk. Lactase is intestinal disaccharidase that catalyzes the lactose hydrolysis. The lactase gene LCT controls biological function of the enzyme. The age-related genetically determined feature of disaccharide expression, epigenetic factors, and natural selection with persistent tolerance to milk sugar throughout lifetime has divided the human population according to the LCT gene into two phenotypes: lactase persistent and lactase non-persistent. There is conflicting evidence that the latter phenotype is associated with low calcium absorption and the development of osteoporosis. The regular use of fermented probiotic dairy products by individuals with the lactase non-persistence phenotype ensures the accumulation of peak bone mineralization and prevents osteoporosis.

Acute Digestive Symptoms and Lactose Malabsorption to Cow Milk or Sheep Milk in Female Dairy Avoiders

Objectives Sheep milk (SM) is compositionally different from cow milk (CM), but maintains the nutritional benefits of CM, making it a potential alternative for CM avoiders. While dairy avoidance is often due to intolerance to lactose, which is also found in SM, there are consumer anecdotal reports that SM is better tolerated than CM. Thus, this clinical trial was undertaken to assess acute digestive comfort and lactose malabsorption comparing SM and CM in female dairy avoiders. Methods In a double-blinded, randomized cross over trial, 30 dairy avoiding females (aged 20–30 years) drank 650 mL of SM or CM (reconstituted from spray dried powder) following an overnight fast, on separate occasions at least one week apart. Blood samples were collected for single nucleotide polymorphisms of the LCT gene (lactase gene; C/T13910 and G/A22018). Breath H2 and visual analog scale (VAS) digestive symptom scores were recorded at fasting and regular intervals over 4 h after ingestion. Results Genotyping showed 80% of the dairy avoiders were lactase non-persistent (CC13910 and GG22018 genotype), hence lactose malabsorbers. Digestive symptoms were similar in response to SM and CM, with increased symptoms; abdominal cramps, rumbling, bloating, belching, flatulence, and nausea, after the ingestion of either milk (P &lt; 0.05). Breath H2 was greater after CM (75 ± 10 ppm), than SM (52 ± 8 ppm at 180 min; P = 0.013) which may be due to greater lactose content in reconstituted CM than SM (30.6 vs 23.0 g). Conclusions The differing composition of SM did not alter adverse digestive symptoms after a single portion relative to CM, although the lower lactose content reduced breath H2 response in SM. However, tolerance to SM should be further investigated with lactose matched milk (as occurs naturally) and in non-lactose related dairy intolerance to elucidate if these individuals could benefit from SM. Funding Sources This study was funded by AgResearch PreSeed Fund, AgResearch Strategic Science Investment Fund, Blue River Dairy, and Spring Sheep Milk Company.

Sex-Specific Associations of Trimethylamine-N-Oxide and Zonulin with Signs of Depression in Carbohydrate Malabsorbers and Nonmalabsorbers

Background. The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA. Methods. Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T-13910 polymorphism genotyping and fructose H2/CH4 breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire. Results. The median TMAO and zonulin serum concentrations were 2.66 (1.93–4.14) μmol/L and 40.83 (34.73–47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P=0.011, ρ=0.160). The strongest correlations were observed in 87 females (P=0.010, ρ=0.274) and 49 males (P=0.027, ρ=0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P=0.062, ρ=−0.269). Conclusion. This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

Polymorphism of C/T-13910 lactase gene and anthropometric data of girls born in Samara

Objectives -to assess the prevalence of C/T-13910 polymorphism of the lactase gene in the population of children in Samara and to identify the relationship with height, body weight and body mass index. Material and methods. The study included 103 girls aged 3-6 years. Their height and body weight were measured, and buccal samples were taken to genotype lactase activity (determining the C/T-13910 variant). Results. In girls born and living in Samara, the frequency of allele 13910-T was 48.6%. The СС genotype was detected in 51.4%, the СГ genotype in 37.9% and the TT genotype in 10.7%. There was no statistically significant relationship between genotype and body weight and height, but all children with the TT genotype had a height of more than 25 percentiles, the vast majority of overweight and obese girls (91%) had the СС genotype or the CT genotype.