Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells.

Dendritic cells (DCs) have a role in the development and activation of self-reactive pathogenic T cells1,2. Genetic variants that are associated with the function of DCs have been linked to autoimmune disorders3,4, and DCs are therefore attractive therapeutic targets for such diseases. However, developing DC-targeted therapies for autoimmunity requires identification of the mechanisms that regulate DC function. Here, using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies, we identify a regulatory loop of negative feedback that operates in DCs to limit immunopathology. Specifically, we find that lactate, produced by activated DCs and other immune cells, boosts the expression of NDUFA4L2 through a mechanism mediated by hypoxia-inducible factor 1α (HIF-1α). NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs that are involved in the control of pathogenic autoimmune T cells. We also engineer a probiotic that produces lactate and suppresses T cell autoimmunity through the activation of HIF-1α-NDUFA4L2 signalling in DCs. In summary, we identify an immunometabolic pathway that regulates DC function, and develop a synthetic probiotic for its therapeutic activation.

Dairying, diseases and the evolution of lactase persistence in Europe.

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years1. Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions2,3. Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution.

Population genomics of the Viking world.

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.

Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying.

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis."

Proposed mechanism for the selection of lactase persistence in childhood.

Lactase persistence/persistent (LP), the ability to express the lactase enzyme in adults, is one of the most strongly selected phenotypes in humans. It is encoded by at least five genetic variants that have rapidly become widespread in various human populations. The underlying selective mechanism is not clear however, because dairy products in general are well tolerated in adults, even by lactase non-persistence/persistent (LNP) individuals. Cultural adaptations to milk consumption, notably fermentation and transformation, which can provide most of the energy (protein, fat) to both LP and LNP individuals without any associated cost seem to have been common in ancient societies. Here, we propose that selection for LP occurred through increased glucose/galactose (energy) from fresh milk intake in early childhood, a crucial period for growth. At the age of weaning indeed, lactase activity has already begun to decline in LNP individuals so the gain in energy from fresh milk by LP children represents a major fitness increase.

Effect of lactase supplementation on infant colic: Systematic review of randomized controlled trials.

To systematically review evidence on the efficacy and safety of using a lactase supplementation for managing infant colic. The MEDLINE, EMBASE, and Cochrane Library databases were searched (up to September 2023) for randomized controlled trials (RCTs) comparing oral lactase supplementation with placebo or no intervention in infants younger than 6 months old with infant colic. The risk of bias was assessed using the revised version of the Cochrane risk-of-bias tool. Outcomes measured were selected according to a standardized core outcome set. Five RCTs involving a total of 391 infants were identified. Three RCTs reported reduced crying duration, but one showed effect only in a compliant group (40.4%, p = 0.0052). A meta-analysis of two RCTs found no difference in crying duration and fussing time during 1 week of lactase treatment compared with placebo (mean difference [MD] -17.66 min/day, 95% confidence interval [CI], -60.8 to 25.5; I2 = 68% and MD 2.75, 95% CI, -58.2 to 57.2; I2 = 80%, respectively). Other outcomes were assessed only in individual studies or not reported. The risk of bias was low in only one RCT, high in three, and raised some concerns in one. While individual trials have shown some promise, the overall evidence for the efficacy of lactase supplementation in treating infant colic remain inconclusive. Further well-designed RCTs are necessary to determine the effects of lactase on managing infant colic.

Added Value of 13C Analysis in Breath Tests in H2-Negative Subjects to Diagnose Lactose Malabsorption: A Proof of Concept Study.

INTRODUCTION: Diagnosing lactose malabsorption is usually based on hydrogen excretion in breath after a lactose challenge. However, a proportion of subjects with lactose malabsorption will not present a rise in hydrogen. Measuring excretion of methane or stable isotope labeled 13CO2 after ingestion of 13C-lactose has been proposed to mitigate this problem. OBJECTIVE: The aim of the study was to assess the performance of measuring methane and 13CO2 in individuals with normal hydrogen excretion compared to a genetic lactase non-persistence test. METHODS: Individuals referred for lactose breath testing and healthy controls were included. Participants received 13C-enriched lactose, performed breath testing, and underwent genotyping for a marker of lactase non-persistence (13910C*T). Using genotype as gold standard, the performance of measuring methane and 13CO2 excretion was assessed. RESULTS: 151 subjects participated in the study, 50 of which presented a lactase non-persistent genotype. Of these, 72% were correctly diagnosed through hydrogen excretion of ≥ 20 ppm above baseline. In subjects with normal hydrogen excretion, cumulative 13C excretion had an area under the curve (AUC) of the receiver operating characteristics (ROC) curve of 0.852. Sensitivity was 93% and specificity was 51% for the current cutoff of 14.5%. The optimal cutoff was 12.65% (sensitivity 93%, specificity 70%). The ROC curve of peak methane had an AUC of 0.542 (sensitivity of 14%, specificity of 91% for cutoff ≥ 10 ppm). CONCLUSIONS: In individuals with genetically demonstrated lactase non-persistence and negative hydrogen breath test, the use of 13C-lactose with measurement of 13CO2 excretion and hydrogen is a well-performing test to detect the lactose malabsorption and performs better than methane in our cohort.

Lactase can target cellular differentiation of Acanthamoeba castellanii belonging to the T4 genotype.

The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.

Demographic and Selection Histories of Populations Across the Sahel/Savannah Belt.

The Sahel/Savannah belt harbors diverse populations with different demographic histories and different subsistence patterns. However, populations from this large African region are notably under-represented in genomic research. To investigate the population structure and adaptation history of populations from the Sahel/Savannah space, we generated dense genome-wide genotype data of 327 individuals-comprising 14 ethnolinguistic groups, including 10 previously unsampled populations. Our results highlight fine-scale population structure and complex patterns of admixture, particularly in Fulani groups and Arabic-speaking populations. Among all studied Sahelian populations, only the Rashaayda Arabic-speaking population from eastern Sudan shows a lack of gene flow from African groups, which is consistent with the short history of this population in the African continent. They are recent migrants from Saudi Arabia with evidence of strong genetic isolation during the last few generations and a strong demographic bottleneck. This population also presents a strong selection signal in a genomic region around the CNR1 gene associated with substance dependence and chronic stress. In Western Sahelian populations, signatures of selection were detected in several other genetic regions, including pathways associated with lactase persistence, immune response, and malaria resistance. Taken together, these findings refine our current knowledge of genetic diversity, population structure, migration, admixture and adaptation of human populations in the Sahel/Savannah belt and contribute to our understanding of human history and health.

Human adaptation, demography and cattle domestication: an overview of the complexity of lactase persistence in Africa.

Lactase persistence (LP) is a genetically-determined trait that is prevalent in African, European and Arab populations with a tradition of animal herding and milk consumption. To date, genetic analyses have identified several common variants that are associated with LP. Furthermore, data have indicated that these functional alleles likely have been maintained in pastoralist populations due to the action of recent selection, exemplifying the ongoing evolution of anatomically modern humans. Additionally, demographic history has also played a role in the geographic distribution of LP and associated alleles in Africa. In particular, the migration of ancestral herders and their subsequent admixture with local populations were integral to the spread of LP alleles and the culture of pastoralism across the continent. The timing of these demographic events was often correlated with known major environmental changes and/or the ability of domesticated cattle to resist/avoid infectious diseases. This review summarizes recent advances in our understanding of the genetic basis and evolutionary history of LP, as well as the factors that influenced the origin and spread of pastoralism in Africa.

Association of Estimated Daily Lactose Consumption, Lactase Persistence Genotype (rs4988235), and Gut Microbiota in Healthy Adults in the United States.

BACKGROUND: Lactase persistence (LP) is a heritable trait in which lactose can be digested throughout adulthood. Lactase nonpersistent (LNP) individuals who consume lactose may experience microbial adaptations in response to undigested lactose. OBJECTIVES: The objective of the study was to estimate lactose from foods reported in the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) and determine the interaction between lactose consumption, LP genotype, and gut microbiome in an observational cross-sectional study of healthy adults in the United States (US). METHODS: Average daily lactose consumption was estimated for 279 healthy US adults, genotyped for the lactase gene -13910G>A polymorphism (rs4988235) by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database. Analysis of covariance was used to identify whether the A genotype (LP) influenced lactose and total dairy consumption, with total energy intake and weight as covariates. The 16S rRNA V4/V5 region, amplified from bacterial DNA extracted from each frozen stool sample, was sequenced using Illumina MiSeq (300 bp paired-end) and analyzed using Quantitative Insights Into Microbial Ecology (QIIME)2 (version 2019.10). Differential abundances of bacterial taxa were analyzed using DESeq2 likelihood ratio tests. RESULTS: Across a diverse set of ethnicities, LP subjects consumed more lactose than LNP subjects. Lactobacillaceae abundance was highest in LNP subjects who consumed more than 12.46 g/d (upper tercile). Within Caucasians and Hispanics, family Lachnospiraceae was significantly enriched in the gut microbiota of LNP individuals consuming the upper tercile of lactose across both sexes. CONCLUSIONS: Elevated lactose consumption in individuals with the LNP genotype is associated with increased abundance of family Lactobacillaceae and Lachnospriaceae, taxa that contain multiple genera capable of utilizing lactose. This trial was registered on clinicaltrials.gov as NCT02367287.

Why and when was lactase persistence selected for? Insights from Central Asian herders and ancient DNA.

The genetic adaptation of humans to the consumption of milk from dairying animals is one of the most emblematic cases of recent human evolution. While the phenotypic change under selection, lactase persistence (LP), is known, the evolutionary advantage conferred to persistent individuals remains obscure. One informative but underappreciated observation is that not all populations whose ancestors had access to milk genetically adapted to become lactase persistent. Indeed, Central Asian herders are mostly lactase nonpersistent, despite their significant dietary reliance on dairy products. Investigating the temporal dynamic of the -13.910:C>T Eurasian mutation associated with LP, we found that, after its emergence in Ukraine 5,960 before present (BP), the T allele spread between 4,000 BP and 3,500 BP throughout Eurasia, from Spain to Kazakhstan. The timing and geographical progression of the mutation coincides well with the migration of steppe populations across and outside of Europe. After 3,000 BP, the mutation strongly increased in frequency in Europe, but not in Asia. We propose that Central Asian herders have adapted to milk consumption culturally, by fermentation, and/or by colonic adaptation, rather than genetically. Given the possibility of a nongenetic adaptation to avoid intestinal symptoms when consuming dairy products, the puzzle then becomes this: why has LP been selected for at all?

The influence of Scandinavian presence on Greenlandic lactase persistence.

BACKGROUND: The study aims to estimate the prevalence of lactase non-persistence (LNP) among Greenlandic Inuit and Scandinavians living in Nuuk and East Greenland. The C to T transition in LCT - 13910 (rs4988235) is an autosomal inherited variant that provides the ability to lifelong lactase production, necessary to digest milk. The transition is very common in North European populations. However, LNP has only been sparsely studied in Greenland and never in Eastern Greenland, and genotype data has not previously been reported. METHODS: Whole blood samples were collected from 535 participants, and rs4988235 was typed using a PCR-based method. Ethnicity was defined by parents' place of birth. Results were compared between East and West Greenland and Inuit and Scandinavians using Pearson's Chi2 test. RESULTS: 82.2% of the participants were Inuit, and 17.8% were of Scandinavian ancestry. Among Inuit, 88.5% had LNP compared to 7.5% among Scandinavians (p < 0.001). The prevalence of LNP in Inuit varied significantly between East and West Greenland (p < 0.001). In the capital, 67.6% of Inuit had LNP compared to 98.6% in Tasiilaq and 100% in the villages around Tasiilaq. DISCUSSION: The difference in LNP between East and West Greenland and the Inuit and Scandinavian population found in our study suggests that the original Inuit population was lactose maldigesters. Our findings suggest that the -13910 T allele was introduced into the original Inuit population by the Danes.

Milk intake, lactase persistence genotype, plasma proteins and risks of cardiovascular events in the Swedish general population.

To investigate the associations of milk intake (non-fermented and fermented milk), lactase persistence (LCT-13910 C/T) genotype (a proxy for long-term non-fermented milk intake), and gene-milk interaction with risks of cardiovascular disease (CVD) and CVD mortality. Also, to identify the CVD-related plasma proteins and lipoprotein subfractions associated with milk intake and LCT-13910 C/T genotype. The prospective cohort study included 20,499 participants who were followed up for a mean of 21 years. Dietary intake was assessed using a modified diet history method. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After adjusting for sociodemographic and lifestyle factors, higher non-fermented milk intake was significantly associated with higher risks of coronary heart disease (CHD) and CVD mortality, whereas higher fermented milk intake was significantly associated with lower risks of CVD and CVD mortality. The genotype associated with higher milk (mainly non-fermented) intake was positively associated with CHD (CT/TT vs. CC HR = 1.27; 95% CI: 1.03, 1.55) and CVD (HR = 1.22; 95% CI: 1.05, 1.42). The association between rs4988235 genotype and CVD mortality was stronger in participants with higher milk intake than among participants with lower intake (P for interaction < 0.05). Furthermore, leptin, HDL, and large HDL were associated with non-fermented milk intake, while no plasma proteins or lipoprotein subfractions associated with fermented milk intake and LCT-13910 C/T genotype were identified. In conclusion, non-fermented milk intake was associated with higher risks of CHD and CVD mortality, as well as leptin and HDL, whereas fermented milk intake was associated with lower risks of CVD and CVD mortality.

DNA polymorphisms associated with lactase persistence, self-perceived symptoms of lactose intolerance, milk and dairy consumption, and ancestry, in the Uruguayan population.

Uruguay has one of the highest per capita milk intakes worldwide, even with a limited supply of lactose-free products; furthermore, the admixed nature of its population is well known, and various frequencies of lactase persistence (LP) are observed in the source populations. We aimed to contribute to the understanding of the relation between allelic variants associated with LP, milk consumption, digestive symptoms, and genetic ancestry in the Uruguayan population. Samples of saliva or peripheral blood were collected from 190 unrelated individuals from two regions of Uruguay, genotypes for polymorphic sites in a fragment within the LCT enhancer were determined and allelic frequencies calculated in all of them. Data were collected on frequency of milk and dairy consumption and self-reported symptoms in a subsample of 153 individuals. Biparental and maternal ancestry was determined by analyzing individual ancestry markers and mitochondrial DNA. Twenty-nine percentage of individuals reported symptoms attributed to the ingestion of fresh milk, with abdominal pain, bloating and flatulence being the most frequent. European LP-associated allele T-13910 showed a frequency of 33%, while other LP-associated alleles like G-13915 and T-14011 were observed in very low frequencies. Associations between self-reported symptoms, fresh milk intake, and C/T-13910 genotype were statistically significant. No evidence of association between genetic ancestry and C/T-13910 was found, although individuals carrying one T-13910 allele appeared to have more European ancestry. In conclusion, the main polymorphism capable of predicting lactose intolerance in Uruguayans is C/T-13910, although more studies are required to unravel the relation between genotype and lactase activity, especially in heterozygotes.

Molecular and isotopic evidence for milk, meat, and plants in prehistoric eastern African herder food systems.

The development of pastoralism transformed human diets and societies in grasslands worldwide. The long-term success of cattle herding in Africa has been sustained by dynamic food systems, consumption of a broad range of primary and secondary livestock products, and the evolution of lactase persistence (LP), which allows digestion of lactose into adulthood and enables the milk-based, high-protein, low-calorie diets characteristic of contemporary pastoralists. Despite the presence of multiple alleles associated with LP in ancient and present-day eastern African populations, the contexts for selection for LP and the long-term development of pastoralist foodways in this region remain unclear. Pastoral Neolithic (c 5000 to 1200 BP) faunas indicate that herders relied on cattle, sheep, and goats and some hunting, but direct information on milk consumption, plant use, and broader culinary patterns is rare. Combined chemical and isotopic analysis of ceramic sherds (n = 125) from Pastoral Neolithic archaeological contexts in Kenya and Tanzania, using compound-specific δ13C and Δ13C values of the major fatty acids, provides chemical evidence for milk, meat, and plant processing by ancient herding societies in eastern Africa. These data provide the earliest direct evidence for milk product consumption and reveal a history of reliance on animal products and other nutrients, likely extracted through soups or stews, and plant foods. They document a 5,000-y temporal framework for eastern Africa pastoralist cuisines and cultural contexts for selection for alleles distinctive of LP in eastern Africa.

A Comprehensive Look at the -13910 C>T LCT Gene Polymorphism as a Molecular Marker for Vitamin D and Calcium Levels in Young Adults in Central and Eastern Europe: A Preliminary Study.

Intolerance to dairy products resulting from the abnormal digestion of milk sugar (lactose) is a common cause of human gastrointestinal disorders. The aim of this study was to show that the -13910 C>T LCT gene polymorphism, together with genotypes of selected VDR gene polymorphisms and diet and nutritional status parameters, can impact the prevalence of vitamin D and calcium deficiency in young adults. This study was conducted on a group of 63 people, which comprised 21 individuals with primary adult lactase deficiency, and a control group of 42 individuals with no hypolactasia. The LCT and VDR gene genotypes were assessed using PCR restriction fragment length polymorphism (PCR-RFLP) analysis. A validated HPLC method was used to determine serum concentrations of 25(OH)D2 and 25(OH)D3. Atomic absorption spectrometry was used to determine calcium levels. Their diets (self-reported 7-day estimated food record), estimated calcium intakes based on the ADOS-Ca questionnaire and basic anthropometric parameters were assessed. The CC genotype associated with hypolactasia was found in 33.3% of the subjects. The presence of the CC variant of the LCT gene polymorphism in the study group of young Polish adults was found to be associated with significantly lower milk (134.7 ± 66.7 g/d vs. 342.5 ± 176 g/d; p = 0.012) and dairy product consumption (78.50 ± 36.2 g/d vs. 216.3 ± 102 g/d; p = 0.008) compared with lactase persistence. At the same time, people with adult-type primary intolerance were found to have statistically significant lower serum levels of vitamin D and calcium (p < 0.05). There was a higher chance of vitamin D and calcium deficiency and a lower intake in the group exhibiting lactase non-persistence (OR > 1). The AA variant of the VDR gene's BsmI polymorphism present in people with hypolactasia may further contribute to an increased risk of vitamin D deficiency. Exclusion of lactose from the diet, combined with impaired vitamin D metabolism, may also lead to inhibited calcium absorption by the body. Further research should be carried out on a larger group of subjects to clarify the relationship between lactase activity and vitamin D and calcium levels in young adults.

Influence of Pasteurization on Maillard Reaction in Lactose-Free Milk.

In order to improve the safety and quality of lactose-free milk (LFM) Maillard reaction products (MRPs), this study used raw cow's milk as raw material and lactase hydrolysis to prepare LFM, which was heat-treated using pasteurization and then placed in storage temperatures of 4 °C, 25 °C and 37 °C to investigate the changes in the Maillard reaction (MR). The results of the orthogonal test showed that the optimal conditions for the hydrolysis of LFM are as follows: the hydrolysis temperature was 38 °C, the addition of lactase was 0.03%, and the hydrolysis time was 2.5 h. Under these conditions, the lactose hydrolysis rate reached 97.08%, and the lactose residue was only 0.15 g/100 g as determined by high-performance liquid chromatography (HPLC), complying with the standard of LFM in GB 28050-2011. The contents of furoamic acid and 5-hydroxymethylfurfural were determined by high-performance liquid chromatography, the color difference was determined by CR-400 color difference meter, and the internal fluorescence spectrum was determined by F-320 fluorescence spectrophotometer. The test results showed that the variation range of furosine in lactose-free milk after pasteurization was 44.56~136.45 mg/100g protein, the range of 5-hydroxymethylfurfural (HMF) was 12.51~16.83 mg/kg, the color difference ranges from 88.11 to 102.53 in L*, from -0.83 to -0.10 in a*, and from 1.88 to 5.47 in b*. The furosine content of LFM during storage at 4, 25, and 37 °C ranged from 44.56 to 167.85, 44.56 to 287.13, and 44.56 to 283.72 mg/100 g protein, respectively. The average daily increase in protein content was 1.18-3.93, 6.46-18.73, and 15.7-37.66 mg/100 g, respectively. The variation range of HMF was 12.51~17.61, 12.51~23.38, and 12.51~21.1 mg/kg, and the average daily increase content was 0.03~0.07, 0.47~0.68, and 0.51~0.97 mg/kg, respectively. During storage at 4 °C, the color difference of LFM ranged from 86.82 to 103.82, a* ranged from -1.17 to -0.04, and b* ranged from 1.47 to 5.70. At 25 °C, color difference L* ranges from 72.09 to 102.35, a* ranges from -1.60 to -0.03, b* ranges from 1.27 to 6.13, and at 37 °C, color difference L* ranges from 58.84 to 102.35, a* ranges from -2.65 to 1.66, and b* ranges from 0.54 to 5.99. The maximum fluorescence intensity (FI) of LFM varies from 131.13 to 173.97, 59.46 to 173.97, and 29.83 to 173.97 at 4, 25, and 37 °C. In order to reduce the effect of the Maillard reaction on LFM, it is recommended to pasteurize it at 70 °C-15 s and drink it as soon as possible during the shelf life within 4 °C.

[The effect of the FODMAP and rebamipid diet on the activity of disaccharidases in patients with enteropathy with impaired membrane digestion].

AIM: To compare the effect of a diet low in fermentable oligo-, di-, monosaccharides and polyols (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAP) and rebamipide on carbohydrate tolerance and disaccharidases activity in patients with maldigestive enteropathy (ENMP). MATERIALS AND METHODS: The study included 61 patients with ENMP with reduced small intestine carbohydrases. Their glucoamylase activity was 100 ng glucose/mg tissue × min (quartile 53, 72), maltase - 504 (quartile 258, 708), sucrase - 43 (quartile 25, 58), lactase - 8 (quartile 4, 20). Group 1 included 19 people on a low FODMAP diet. The 2nd group included 42 patients who were on a normal diet and received rebamipide 300 mg/day. Patients were monitored weekly for 8 weeks. RESULTS: In 16 patients of the 1st group, abdominal pain and stool disorders decreased, in 15 patients, swelling and rumbling in the abdomen stopped. Glucoamylase activity increased to 196 (quartile 133, 446, р<0.024) ng glucose/mg tissue × min, maltase activity increased to 889 (quartile 554, 1555, p<0.145), sucrase activity increased to 67 (quartile 43, 175, p<0.039), lactase activity increased to 13 (quartile 9, 21, p<0.02). After the diet was discontinued, intestinal symptoms in patients of group 1 resumed. In 27 patients of the 2nd group after 4 weeks dyspeptic manifestations decreased, in 34 patients the tolerability of products containing FODMAP improved. Continuation of treatment up to 8 weeks contributed to a further improvement in well-being. Glucoamylase activity increased after 4 and 8 weeks to 189 (quartile 107, 357, p<0.013) and 203 (quartile 160, 536, p<0.005), respectively; maltase - up to 812 (quartile 487, 915, p<0.005) and 966 (quartile 621, 2195, р<0.0012); sucrases - up to 60 (quartile 34, 105, p<0.013) and 75 (quartile 52, 245, р=0.003); lactase - up to 12 (quartile 8, 12, p<0.132) and 15 ng glucose/mg tissue × min (quartile 10, 20, р<0.092). CONCLUSION: The clinical symptoms of fermentable carbohydrate intolerance and increased membrane enzyme activity are reduced by a low FODMAP diet in patients with ENMT, but clinical symptoms of food intolerance reappear when switching to a normal diet. Treatment with rebamipide improves food tolerance and consistently increases the activity of TSOTS enzymes after 4 and 8 weeks.