Human adaptations to diet: Biological and cultural coevolution.

Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use different subsistence modes. This has resulted in different adaptations, such as differential responses to diseases and different abilities to digest or tolerate certain foods. The shift from a subsistence strategy based on hunting and gathering during the Palaeolithic to a lifestyle based on the consumption of domesticated animals and plants in the Neolithic can be considered one of the most important dietary transitions of Homo sapiens. In this text, we review four examples of gene-culture coevolution: (i) the persistence of the enzyme lactase after weaning, which allows the digestion of milk in adulthood, related to the emergence of dairy farming during the Neolithic; (ii) the population differences in alcohol susceptibility, in particular the ethanol intolerance of Asian populations due to the increased accumulation of the toxic acetaldehyde, related to the spread of rice domestication; (iii) the maintenance of gluten intolerance (celiac disease) with the subsequent reduced fitness of its sufferers, related to the emergence of agriculture and (iv) the considerable variation in the biosynthetic pathway of long-chain polyunsaturated fatty acids in native populations with extreme diets.

Infant milk formula, produced by membrane filtration, promotes mucus production in the upper small intestine of young pigs.

Human breast milk promotes maturation of the infant gastrointestinal barrier, including the promotion of mucus production. In the quest to produce next generation infant milk formula (IMF), we have produced IMF by membrane filtration (MEM-IMF). With a higher quantity of native whey protein, MEM-IMF more closely mimics human breast milk than IMF produced using conventional heat treatment (HT-IMF). After a 4-week dietary intervention in young pigs, animals fed a MEM-IMF diet had a higher number of goblet cells, acidic mucus and mucin-2 in the jejunum compared to pigs fed HT-IMF (P < 0.05). In the duodenum, MEM-IMF fed pigs had increased trypsin activity in the gut lumen, increased mRNA transcript levels of claudin 1 in the mucosal scrapings and increased lactase activity in brush border membrane vesicles than those pigs fed HT-IMF (P < 0.05). In conclusion, MEM-IMF is superior to HT-IMF in the promotion of mucus production in the young gut.

Prebiotic Strategies to Manage Lactose Intolerance Symptoms.

Lactose intolerance, which affects about 65-75% of the world's population, is caused by a genetic post-weaning deficiency of lactase, the enzyme required to digest the milk sugar lactose, called lactase non-persistence. Symptoms of lactose intolerance include abdominal pain, bloating and diarrhea. Genetic variations, namely lactase persistence, allow some individuals to metabolize lactose effectively post-weaning, a trait thought to be an evolutionary adaptation to dairy consumption. Although lactase non-persistence cannot be altered by diet, prebiotic strategies, including the consumption of galactooligosaccharides (GOSs) and possibly low levels of lactose itself, may shift the microbiome and mitigate symptoms of lactose consumption. This review discusses the etiology of lactose intolerance and the efficacy of prebiotic approaches like GOSs and low-dose lactose in symptom management.

EVALUATION OF AGREEMENT BETWEEN C/T-13910 POLYMORPHISM GENOTYPING RESULTS AND LACTOSE TOLERANCE TEST RESULTS: A RETROSPECTIVE POPULATION-BASED STUDY IN BRAZIL.

BACKGROUND: Lactose tolerant test (LTT) is the most broadly used diagnostic test for lactose intolerance in Brazil, is an indirect, minimally invasive and a low-cost test that is widely available in primary care and useful in clinical practice. The C/T-13910 polymorphism in lactase persistence has been well characterized in Caucasian populations, but there are no studies evaluating the concordance between C/T-13910 polymorphism genotyping results and LTT results in Brazil, where the population is highly mixed. OBJECTIVE: We aimed to evaluate agreement between presence of C/T-13910 polymorphism genotyping and malabsorption in LTT results. METHODS: This is a retrospective analysis of a Brazilian population whose data were collected from a single laboratory database present in several Brazilian states. Results of individuals who underwent both genetic testing for lactose intolerance (C/T-13910 polymorphism genotyping) and an LTT from April 2016 until February 2019 were analysed to evaluate agreement between tests. Groups were classified according to age (<10-year-old (yo), 10-17 yo, ≥18 yo groups) and state of residence (São Paulo or Rio Grande do Sul). Results: Among the 404 patients evaluated, there was agreement between the genotyping and LTT results in 325 (80.4%) patients and discordance in 79 (19.6%) patients (k=0.42 -moderate agreement). Regarding the genotype, 47 patients with genotype C/C (lactase nonpersistence) had normal LTT results, and 32 with genotype C/T or T/T (indicating lactase persistence) had abnormal LTT results. Neither age nor state of residence (Rio Grande do Sul or São Paulo) affected the agreement between test results. CONCLUSION: Considering the moderate agreement between C/T-13910 polymorphism genotyping and LTT results (κ=0.42) in the Brazilian population, we hypothesize that an analysis of other polymorphisms could be a strategy to improve the agreement between genotyping and established tests and suggest that additional studies should focus on exploring this approach. BACKGROUND: • Lactose intolerance is highly prevalent and may be implicated as a cofactor, or as a differential diagnosis, in many gastrointestinal conditions. BACKGROUND: • The C/T-13910 polymorphism in lactase persistence is well characterized in Caucasian populations for lactase persistence. BACKGROUND: • Concordance between genotyping and functional tests does not occur in all patients. BACKGROUND: • Brazil has a highly mixed population and knowledge regarding presence of other polymorphisms is of importance in clarifying difficult cases.

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.

Variant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes.

Cow's milk is frequently included in the human diet, but the relationship between milk intake and type 2 diabetes (T2D) remains controversial. Here, using data from the Hispanic Community Health Study/Study of Latinos, we show that in both sexes, higher milk intake is associated with lower risk of T2D in lactase non-persistent (LNP) individuals (determined by a variant of the lactase LCT gene, single nucleotide polymorphism rs4988235 ) but not in lactase persistent individuals. We validate this finding in the UK Biobank. Further analyses reveal that among LNP individuals, higher milk intake is associated with alterations in gut microbiota (for example, enriched Bifidobacterium and reduced Prevotella) and circulating metabolites (for example, increased indolepropionate and reduced branched-chain amino acid metabolites). Many of these metabolites are related to the identified milk-associated bacteria and partially mediate the association between milk intake and T2D in LNP individuals. Our study demonstrates a protective association between milk intake and T2D among LNP individuals and a potential involvement of gut microbiota and blood metabolites in this association.

A long-term survey of Serratia spp. bloodstream infections revealed an increase of antimicrobial resistance involving adult population.

Serratia spp. is a well-recognized pathogen in neonates; however, limited data are available in adults. We studied microbiological and clinical characteristics of Serratia spp. causing bloodstream infections (BSI) in our institution (January 2005-July 2020). Overall, 141 BSI episodes affecting 139 patients were identified and medical records reviewed. Antimicrobial susceptibility was recovered from our informatics system and 118 isolates from 116 patients were available for further microbiological studies. Whole genome sequencing (WGS) was completed in 107 isolates. Incidence of Serratia BSI was 0.3/1000 overall admissions (range 0.12-0.60), with maximum prevalence (27 episodes, 19.1%) during 2017-2018. Relevant patients' clinical characteristics were 71.9% ≥60 years (n = 100), with high comorbidity rates (49%, ≥2), 23 (74.2%) of them died within 1 month of the BSI episode. WGS identified all isolates as Serratia marcescens when Kraken bioinformatics taxonomic tool was used despite some which were identified as Serratia nematodiphila (32/118) or Serratia ureilytica (5/118) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Nevertheless, when using MASH distance, Serratia nevei (63/107), S. ureilytica (38/107), and S. marcescens (6/107) were assigned. Carbapenemase (blaVIM-1) and extended-spectrum ß-lactases (ESBL) (blaSHV-12) genes were found in seven and three isolates, respectively, one of them expressing both genes. The worldwide-disseminated IncL/M scaffold plasmid was identified in six VIM producers. Four genotypes were established based on their virulence factors and resistome. Serratia spp. emerged as a relevant nosocomial pathogen causing BSI in elderly patients in our hospital, particularly in recent years with a remarkable increase in antibiotic resistance. ESBL and carbapenemases production related to plasmid dissemination are particularly noteworthy.IMPORTANCESerratia spp. is the third most frequent pathogen involved in outbreaks at neonatal facilities and is primarily associated with bacteremia episodes. In this study, we characterized all causing bloodstream infection (BSI) in patients admitted to our hospital during a 16-year period (2005-2020). Despite having no neonatal intensive care unit in our hospital, this study revealed that Serratia spp. is a relevant pathogen causing BSI in elderly patients with high comorbidity rates. A significant increase of antimicrobial resistance was detected over time, particularly in 2020 and coinciding with the coronavirus disease (COVID-19) pandemic and nosocomial spread of multidrug-resistant Serratia spp. isolates. extended-spectrum ß-lactases and carbapenemases genes associated with plasmid dissemination, typically detected in other Enterobacterales species, were also identified, reinforcing the role of Serratia spp. in the antimicrobial resistance landscape. Additionally, this work highlights the need to reclassify the species of Serratia, since discrepancies were observed in the identification when using different tools.

Lactose Intolerance - Single Nucleotide Polymorphisms and Treatment.

The majority (about 70%) of the world's population suffers from lactose intolerance. Lactose intolerance leads to long-term discomfort when consuming milk and dairy products, and hence, to their avoidance. Consequently, the intake of important nutrients is reduced, which potentially has a negative impact on the overall health. Knowing the condition - lactose intolerance - will prevent people from unnecessarily restricting dairy products in their diets. In this study, lactose synthesis and catabolism in the human body are presented, also the types of lactose intolerance, as well as the methods of diagnosing this condition, are discussed. Special attention is paid to the genetic causes of this discomfort and to the tests that can be performed. Solutions for the treatment of lactose intolerance have also been proposed, both up-to-date and easily applicable, as well as future developments.

This review highlights the lactose pathway ­ from the mammary gland production to recipient gut hydrolysis.Lactose intolerance associated SNPs known so far are presented and discussed.Advice for people with lactose intolerance is presented in the form of possible treatments and healthy feeding behaviors.

A Genetic Lab-on-Phone Test for Point-of-Care Diagnostic of Lactose Intolerance near Patient and in less than 90 Minutes.

BACKGROUND: The -13910 C/T single nucleotide polymorphism located within the MCM6 gene, an enhancer region located upstream of the lactase-phlorizin hydrolase gene, is associated with lactase persistence/non-persistence traits among the Caucasian population. The performance of a new point-of-care CE-IVD (In Vitro Diagnostic) marked isothermal lab-on-phone lactose intolerance assay, using crude samples, was assessed in comparison with Sanger sequencing using purified DNA, as reference method. METHODS: The study was conducted following a non-probability sampling using direct buccal swab (n = 63) and capillary blood (n = 43) clinical samples from a total of 63 volunteers. A 3 × 3 confusion matrix/contingency table was used to evaluate the performance of the isothermal lab-on-phone lactose intolerance assay. RESULTS: The isothermal lab-on-phone lactose intolerance assay successfully detected the -13910 C/T variant with a limit of detection of 5 cells/assay and demonstrated an overall accuracy of 98.41% (95% CI, 91.47%-99.96%) for buccal swab samples and 100% (95% CI, 91.19%-100%) for capillary blood, taking just 90 min from sample to result, with only 2 min hands-on. CONCLUSIONS: The lab-on-phone pocket-sized assay displayed good performance when using direct buccal swab and capillary blood samples, enabling a low-cost, real-time, and accurate genotyping of the -13910 C/T region for the rapid diagnosis of primary lactose intolerance at point-of-care, which enables a prompt implementation of appropriate diet habits and/or intolerance therapies. To our knowledge, this is the first point-of-care genetic test for lactose intolerance to be made available on the market.

Changes in gut microbiota and lactose intolerance symptoms before and after daily lactose supplementation in individuals with the lactase nonpersistent genotype.

BACKGROUND: Approximately 70%-100% of the Asian adult population is lactase nonpersistent (LNP). The literature shows that many individuals with the LNP-genotype can consume ≤12 g of lactose without experiencing gastrointestinal discomfort. Repetitive consumption of lactose may reduce intolerance symptoms via adaptation of the gut microbiota. OBJECTIVE: This study aimed to assess the effects of daily consumption of incremental lactose doses on microbiota composition and function, and intolerance symptoms. METHODS: Twenty-five healthy adults of Asian origin, carrying the LNP-genotype were included in this 12-wk before and after intervention trial. Participants consumed gradually increasing lactose doses from 3 to 6 g to 12 g twice daily, each daily dose of 6 g, 12 g, or 24 g being provided for 4 consecutive weeks. Participants handed-in repeated stool samples and underwent a 25 g lactose challenge hydrogen breath test (HBT) before and after the 12-wk intervention. Daily gastrointestinal symptoms and total symptom scores (TSSs) during the lactose challenge were recorded. RESULTS: A significant increase from 5.5% ± 7.6% to 10.4% ± 9.6% was observed in Bifidobacterium relative abundance after the intervention (P = 0.009), accompanied by a 2-fold increase (570 ± 269 U/g; P < 0.001) in fecal ß-galactosidase activity compared with baseline (272 ± 158 U/g). A 1.5-fold decrease (incremental area under the curve; P = 0.01) in expired hydrogen was observed during the second HBT (38 ± 35 ppm·min), compared with the baseline HBT (57 ± 38 ppm·min). There was a nonsignificant decrease in TSS (10.6 ± 8.3 before compared with 8.1 ± 7.2 after intervention; P = 0.09). Daily consumption of lactose was well tolerated, with mild to no gastrointestinal complaints reported during the intervention. CONCLUSIONS: Increased levels of Bifidobacterium indicate an adaptation of the gut microbiota upon repetitive consumption of incremental doses of lactose, which was well tolerated as demonstrated by reduced expired hydrogen concentrations during the second 25-g lactose HBT. Bifidobacteria metabolize lactose without gas production thereby potentially reducing intestinal gas formation in the gut of individuals with the LNP-genotype. This increased lactose tolerance possibly lifts the necessity to remove nutrient-rich dairy foods completely from the diet. The trial is registered at the International Clinical Trials Registry Platform: NL9516. The effect of dietary lactose in lactase nonpersistent individuals on gut microbiota.

Lactose malabsorption and intolerance: What is the correct management in older adults?

Lactose malabsorption is a very common condition due to intestinal lactase deficiency. Post weaning, a genetically programmed and irreversible reduction of lactase activity occurs in the majority of the world's population. Lactose malabsorption does not necessarily result in gastrointestinal symptoms, i.e. lactose intolerance, which occurs in approximately one third of those with lactase deficiency. In the absence of well-established guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Mainly in particular categories, such as the older adults, the approach to lactose malabsorption may deserve careful considerations. Milk and dairy products are an important supply of a wide range of nutrients that contribute to meet the nutritional needs in different life stages. Dietary composition can significantly impact the mechanisms leading to age-related loss of bone mineral density, skeletal muscle mass or function and overall risk of sarcopenia. Moreover, in the latest years, different lines of evidence have highlighted an association between dairy intake and prevention of chronic diseases as well as all-cause mortality. The aim of this opinion paper is to provide an overview of lactose malabsorption and intolerance in the older adults and their implications in clinical practice.

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.

Higher milk consumption is associated with a lower risk of diabetes mellitus: A case-control study.

BACKGROUND & AIMS: Studies have determined that people with genetically defined lactase non-persistence have lower dairy intake that may lead to an increase risk of various non-communicable diseases. Furthermore, lactase non-persistence itself has been associated with insulin resistance. However, data on lactase non-persistence status and dairy intake in developing countries are sparse. We therefore aimed to define 1) the prevalence of lactase non-persistence among individuals with diabetes and non-diabetes in Thai population and 2) the links between lactase non-persistence, milk consumption, and risk of diabetes mellitus. METHODS: We conducted a case-control study from participants of the National Health Examination Survey. DNA was isolated from the blood for LCT -13910C>T (rs4988235) polymorphism and processed using the Bio-rad c1000 touch thermal cycler and MALDI-TOF Mass Spectrometry MassARRAY Typer v4.0 (Agena Bioscience, San Diego, CA, USA) at the Center for Medical Genomics, Faculty of Medicine Ramathibodi Hospital. Cases were participants with previously diagnosed diabetes mellitus or fasting plasma glucose ≥126 mg/dL (n = 1,756) vs. the controls (n = 2,380). RESULTS: We included 4,136 participants, 62% female, and 98.8% were > 30 years old. Homozygous CC genotype (i.e., lactase non-persistence) was noted in 98.6% and only 1.4% carried heterozygous CT. Most (76%) consumed milk <1 portion/month. Participants with either CC or CT genotype had comparable milk consumption and the risk of diabetes mellitus. Males, older adults, and lower education had a lower chance of consuming milk at least one portion per month. Besides various baseline variables, we found that higher milk consumption was associated with a lower DM risk (P = .01). CONCLUSION: The prevalence of lactase non-persistence in Thai population is very high. A significant difference in milk consumption frequency in relation to the lactase non-persistence status was not found. However, higher milk consumption is associated with a lower risk of diabetes mellitus.

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.

Efficient removal of pharmaceutical contaminants from water and wastewater using immobilized laccase on activated carbon derived from pomegranate peels.

In this study, pomegranate peels (PPs) as an abundant fruit processing waste was used to produce cost-effective, eco-friendly, and high-quality activated carbon. The produced carbon (fossil free activated carbon) was used for immobilizing laccase to remove a range of emerging pollutants namely diclofenac, amoxicillin, carbamazepine, and ciprofloxacin from water and wastewater. The loaded activated carbon by laccase (LMPPs) and the unloaded one (MPPs) were characterized using advanced surface chemistry analysis techniques. MPPs was found to have a porous structure with a large surface area and an abundance of acidic functional groups. Laccase immobilization reduced surface area but added active degradation sites. The optimal immobilization parameters were determined as pH 4, 35 °C, and a laccase concentration of 2.5 mg/mL resulting in a 69.8% immobilization yield. The adsorption of the emerging pollutant onto MPPs is best characterized as a spontaneous endothermic process that adheres to the Langmuir isotherm and first-order kinetics. Using synergistic adsorption and enzymatic degradation, the target pollutants (50 mg/L) were eliminated in 2 h. In both water types, LMPPs outperformed MPPs. This study shows that pomegranate peels can effectively be harnessed as an enzyme carrier and adsorbent for the removal of emerging pollutants even from a complex sample matrix. The removal of contaminants from wastewater lasted five cycles, whereas it continued up to six cycles for water.

Lactase deficiency in Russia: multiethnic genetic study.

BACKGROUND: Lactase persistence-the ability to digest lactose through adulthood-is closely related to evolutionary adaptations and has affected many populations since the beginning of cattle breeding. Nevertheless, the contrast initial phenotype, lactase non-persistence or adult lactase deficiency, is still observed in large numbers of people worldwide. METHODS: We performed a multiethnic genetic study of lactase deficiency on 24,439 people, the largest in Russia to date. The percent of each population group was estimated according to the local ancestry inference results. Additionally, we calculated frequencies of rs4988235 GG genotype in Russian regions using the information of current location and birthplace data from the client's questionnaire. RESULTS: The attained results show that among all studied population groups, the frequency of GG genotype in rs4988235 is higher than the average in the European populations. In particular, the prevalence of lactase deficiency genotype in the East Slavs group was 42.8% (95% CI: 42.1-43.4%). We also investigated the regional prevalence of lactase deficiency based on the current place of residence. CONCLUSIONS: Our study emphasizes the significance of genetic testing for diagnostics, i.e., specifically for lactose intolerance parameter, as well as the scale of the problem of lactase deficiency in Russia which needs to be addressed by the healthcare and food sectors.

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.