ABSTRACT
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.
Subject(s)
Lactose Intolerance , Humans , Lactose Intolerance/genetics , Lactose , Lactase/genetics , Abdominal Pain , Biological Evolution , PrebioticsABSTRACT
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.
Subject(s)
Breath Tests , Carbon Isotopes , Hydrogen , Lactase , Lactose Intolerance , Methane , Humans , Breath Tests/methods , Lactose Intolerance/diagnosis , Lactose Intolerance/genetics , Lactose Intolerance/metabolism , Male , Female , Adult , Hydrogen/analysis , Hydrogen/metabolism , Lactase/metabolism , Lactase/genetics , Methane/metabolism , Methane/analysis , Lactose/metabolism , Lactose/urine , Proof of Concept Study , Middle Aged , Case-Control Studies , Carbon Dioxide/metabolism , Genotype , Young AdultABSTRACT
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.
Subject(s)
Lactose Intolerance , Humans , Child , Lactose Tolerance Test , Brazil , Lactose Intolerance/diagnosis , Lactose Intolerance/genetics , Genotype , Retrospective Studies , Lactase/geneticsABSTRACT
Cow's milk (CM) is a healthy food consumed worldwide by individuals of all ages. Unfortunately, "lactase-deficient" individuals cannot digest milk's main carbohydrate, lactose, depriving themselves of highly beneficial milk proteins like casein, lactoalbumin, and lactoglobulin due to lactose intolerance (LI), while other individuals develop allergies specifically against these proteins (CMPA). The management of these conditions differs, and an inappropriate diagnosis or treatment may have significant implications for the patients, especially if they are infants or very young children, resulting in unnecessary dietary restrictions or avoidable adverse reactions. Omics technologies play a pivotal role in elucidating the intricate interactions between nutrients and the human body, spanning from genetic factors to the microbiota profile and metabolites. This comprehensive approach enables the precise delineation and identification of distinct cohorts of individuals with specific dietary requirements, so that tailored nutrition strategies can be developed. This is what is called personalized nutrition or precision nutrition (PN), the area of nutrition that focuses on the effects of nutrients on the genome, proteome, and metabolome, promoting well-being and health, preventing diseases, reducing chronic disease incidence, and increasing life expectancy. Here, we report the opinion of the scientific community proposing to replace the "one size fits all" approach with tailor-made nutrition programs, designed by integrating nutrigenomic data together with clinical parameters and microbiota profiles, taking into account the individual lactose tolerance threshold and needs in terms of specific nutrients intake. This customized approach could help LI patients to improve their quality of life, overcoming depression or anxiety often resulting from the individual perception of this condition as different from a normal state.
Subject(s)
Lactose Intolerance , Milk Hypersensitivity , Infant , Child , Animals , Cattle , Female , Humans , Child, Preschool , Lactose Intolerance/genetics , Lactose Intolerance/diagnosis , Milk , Milk Hypersensitivity/diagnosis , Lactose , Quality of Life , Milk Proteins/adverse effectsABSTRACT
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.
Subject(s)
Lactose Intolerance , Humans , Lactose Intolerance/diagnosis , Lactose Intolerance/genetics , Lactose Intolerance/epidemiology , Lactase/genetics , Point-of-Care Systems , Genotype , Point-of-Care TestingABSTRACT
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.
Subject(s)
Gastrointestinal Microbiome , Lactose Intolerance , Adult , Humans , Lactose Intolerance/genetics , Lactase/genetics , Lactose/metabolism , beta-Galactosidase/genetics , beta-Galactosidase/therapeutic use , Genotype , Hydrogen/therapeutic use , Dietary Supplements , Breath TestsABSTRACT
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.
Subject(s)
Diabetes Mellitus , Lactose Intolerance , Male , Humans , Female , Aged , Adult , Animals , Milk , Lactase/genetics , Case-Control Studies , Risk , Diabetes Mellitus/epidemiology , Diabetes Mellitus/genetics , Genotype , Lactose Intolerance/genetics , Polymorphism, Single NucleotideABSTRACT
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.
Subject(s)
Gastrointestinal Microbiome , Lactose Intolerance , Male , Female , Humans , Adult , United States , Lactose , Lactose Intolerance/genetics , Gastrointestinal Microbiome/genetics , Cross-Sectional Studies , RNA, Ribosomal, 16S/genetics , Dairy Products , Lactase/genetics , GenotypeABSTRACT
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.
Subject(s)
Lactose Intolerance , Humans , Animals , Cattle , Lactose Intolerance/epidemiology , Lactose Intolerance/genetics , Lactase/genetics , Lactose , Genotype , Phenotype , Polymorphism, Single NucleotideABSTRACT
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.
Subject(s)
Lactose Intolerance , Adult , Child , Child, Preschool , Humans , Lactase/genetics , Lactose Intolerance/genetics , MilkABSTRACT
OBJECTIVE: The aim of this study is to investigate the potential genetic etiology of cribra orbitalia noted on human skeletal remains. MATERIALS: We obtained and analyzed ancient DNA of 43 individuals with cribra orbitalia. The analyzed set represented medieval individuals from two cemeteries in western Slovakia, Castle Devín (11th-12th century AD) and Cífer-Pác (8th-9th century AD). METHODS: We performed a sequence analysis of 5 variants in 3 genes associated with anemia (HBB, G6PD, PKLR), which are the most common pathogenic variants in present day of European populations, and one variant MCM6:c.1917 + 326 C>T (rs4988235) associated with lactose intolerance. RESULTS: DNA variants associated with anemia were not found in the samples. The allele frequency of MCM6:c.1917 + 326 C was 0.875. This frequency is higher but not statistically significant in individuals displaying cribra orbitalia compared to individuals without the lesion. SIGNIFICANCE: This study seeks to expand our knowledge of the etiology of cribra orbitalia by exploring the potential association between the lesion and the presence of alleles linked to hereditary anemias and lactose intolerance. LIMITATIONS: A relatively small set of individuals were analyzed, so an unequivocal conclusion cannot be drawn. Hence, although it is unlikely, a genetic form of anemia caused by rare variants cannot be ruled out. SUGGESTIONS FOR FURTHER RESEARCH: Genetic research based on larger sample sizes and in more diverse geographical regions.
Subject(s)
Anemia , Lactose Intolerance , Humans , Pilot Projects , Slovakia , Lactose Intolerance/genetics , CemeteriesABSTRACT
BACKGROUND: Lactose intolerance is defined as the presence of gastrointestinal symptoms, such as bloating, abdominal pain or diarrhoea, after consumption of lactose in individuals with lactose malabsorption. Most cases involve primary lactose intolerance, caused by a loss of activity of the enzyme lactase, needed for digestion of lactose. A traditional method of establishing lactose intolerance is the hydrogen breath test (HBT), accompanied by a questionnaire to document complaints experienced by the patient during the test. Due to knowledge on lactase-persistent alleles, DNA genotyping has become available for the diagnostic work-up for lactose intolerance. Both methods are currently in use. The aim of this study is to provide a definite diagnostic approach for patients suspected of lactose intolerance in a Dutch population. METHODS: In this retrospective, observational study, patients aged 15 years or older were included after presenting to their treating physician with symptoms suggestive of lactose intolerance. HBT, including a questionnaire to document complaints and DNA genotyping of LCT-13,910 C/T was performed for each patient as part of a routine diagnostic work-up. RESULTS: 1101 patients were included (29% men). Positive and negative predictive value, sensitivity and specificity of HBT versus DNA genotyping were 80% (CI 75-84), 97% (CI 96-98), 89% (CI 84-92) and 94% (92-96) respectively. The use of the questionnaire added little diagnostic value. CONCLUSIONS: In a population with a high prevalence of lactase-persistent alleles, we advise to exclude HBT from the diagnostic route for suspected lactose intolerance, and replace it with genotyping of lactase-persistent alleles.
Subject(s)
Lactose Intolerance , Male , Humans , Female , Lactose Intolerance/diagnosis , Lactose Intolerance/genetics , Lactose Intolerance/epidemiology , Lactose , Genotype , Retrospective Studies , Lactase/genetics , Breath Tests/methods , DNA , HydrogenABSTRACT
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.
Subject(s)
Lactose Intolerance , Humans , Animals , Lactose Intolerance/epidemiology , Lactose Intolerance/genetics , Milk , Lactase/genetics , Uruguay , Genotype , DNA, Mitochondrial , Polymorphism, Single NucleotideABSTRACT
Lactase persistence is an autosomal dominant trait characterized by sustained expression of lactase gene throughout adulthood. This trait is mostly prevalent in populations with pastoral or agro-pastoral ancestry and allows lactase persistent individuals to benefit from milk nutrients. Several genetic variants have been identified to be responsible for lactase persistence in different populations and other genetic variants associated with lactase persistence are expected to be found. In this study, we aimed to investigate the lactase persistence phenotype and genotype in two isolated populations, the Iranian Mazani-Shahmirzadi and Afghan Hazaras living in Iran. For this purpose, we genotyped five single nucleotide polymorphisms -13.907C/G, -13.910C/T, -13.913T/C, -13.915T/G and -22.018A/G in 45 Mazanis from Shahmirzad and 50 Hazaras living in the suburb of Tehran. We also investigated lactase persistence by inquiring about digestive symptoms and measuring blood glucose levels after 50g lactose consumption. Our results show that 24.2% of Mazani-Shahmirzadis and 14% of Hazaras are lactase persistent based on blood glucose levels. Genotype investigation shows that only two SNPs, 13.910 C/T and 22.018 A/G display variation in the studied populations. The -13.910*T allele has a frequency of 7.7% in Mazani-Shahmirzadis and 12.7% in Hazaras. The frequency of -22.018*A was 16.6% in Mazani-Shahmirzadis and 17% in Hazaras. Importantly, we found a new genetic variant at -13.913 single nucleotide polymorphism which has not been previously reported. Given that the -13.913 single nucleotide polymorphism is within the enhancer Oct-1 binding site, the presence of this variant could affect lactase gene expression in adults. Further studies are required to elucidate the impact of this variant on LCT gene enhancer function.
Subject(s)
Lactase , Lactose Intolerance , Humans , Blood Glucose , Gene Frequency , Genotype , Iran , Lactase/genetics , Lactose Intolerance/ethnology , Lactose Intolerance/genetics , Phenotype , Polymorphism, Single NucleotideABSTRACT
Primary lactose malabsorption is characterised by a down-regulation of lactase activity after weaning and inability to digest lactose in adulthood. It has been suggested that the historical introduction of dairying led to a positive selection for lactase persistence variants in a regulatory region upstream of the LCT gene. Here, we genotyped 202 Armenian subjects for LCT-13910T, a lactase persistence variant which is widespread in Europeans. The homozygous C/C genotype associated with primary hypolactasia, the heterozygous C/T and the homozygous T/T lactase persistence genotypes were found in 191 (94.6%), 11 (5.4%), and 0 (0.0%) samples, respectively. The frequency for the LCT-13910*T allele was 2.7%. The observed allele frequency of 2.7% for LCT-13910T is even lower than previously reported and supports current phenotypic data about lactose malabsorption in Armenia.
Subject(s)
Lactose Intolerance , Humans , Adult , Lactose Intolerance/genetics , Lactose Intolerance/epidemiology , Lactase/genetics , Alleles , Armenia , Genotype , Gene Frequency , Polymorphism, Single NucleotideABSTRACT
The majority of the world population is lactose intolerant, as 65%-70% of people lose the enzymes to digest lactose after infancy. Yet, in the United States, where lactose intolerance is predicted to affect only 36% of people, this phenomenon is often framed as a deficiency as opposed to the norm. This is because the United States has a higher prevalence of people who are lactase persistent. Lactase persistence is a genetic trait most common among Europeans and some African, Middle Eastern and southern Asian groups with a history of animal domestication and milk consumption. In this study, we take the case of lactose intolerance to examine how popular media maintains biocentric biases. Analysing relevant articles published in The New York Times and Scientific American between 1971 and 2020, we document how ideas about milk, health and race evolve over time. Over this fifty-year period, writers shifted from framing lactose intolerance as racial difference to lactase persistence as evolutionary genetics. Yet, articles on the osteoporosis 'epidemic' and vitamin D deficiency worked to perpetuate lactose intolerance as a health concern and standardise the dairy-heavy American diet. Studying media portrayals of lactose intolerance and lactase persistence, we argue that popular discourses normalise biocentric biases through messages about eating behaviours and health.
Subject(s)
Lactose Intolerance , Animals , Humans , Lactose Intolerance/epidemiology , Lactose Intolerance/genetics , Milk , Lactose , Lactase/genetics , BiasABSTRACT
Giant study of ancient pottery and DNA challenges common evolutionary explanation for lactase persistence.
Subject(s)
Dairying , Farms , Lactase , Lactose Intolerance , Milk , Selection, Genetic , White People , Animals , DNA, Ancient , Dairying/history , Digestion , Europe , Farms/history , History, Ancient , Humans , Lactase/genetics , Lactose Intolerance/enzymology , Lactose Intolerance/genetics , Lactose Intolerance/history , Starvation/epidemiology , White People/genetics , White People/historyABSTRACT
Many clinicians have suboptimal knowledge of evolutionary medicine. This discipline integrates social and basic sciences, epidemiology, and clinical medicine, providing explanations, especially ultimate causes, for many conditions. Principles include genetic variation from population bottleneck and founder effects, evolutionary trade-offs, and coevolution. For example, host-microbe coevolution contributes to the inflammatory and carcinogenic variability of Helicobacter pylori. Antibiotic-resistant strains are evolving, but future therapy could target promutagenic proteins. Ancient humans practicing dairying achieved survival and reproduction advantages of postweaning lactase persistence and passed this trait to modern descendants, delegitimizing lactose intolerance as "disease" in people with lactase nonpersistence. Three evolutionary hypotheses are each relevant to multiple diseases: (i) the polyvagal hypothesis posits that prehistoric adaptation of autonomic nervous system reactions to stress is beneficial acutely but, when continued chronically, predisposes individuals to painful functional gastrointestinal disorders, in whom it may be a biomarker; (ii) the thrifty gene hypothesis proposes genetic adaptation to feast-famine cycles among Pleistocene migrants to America, which is mismatched with Indigenous Americans' current diet and physical activity, predisposing them to obesity, nonalcoholic fatty liver disease, and gallstones and their complications; and (iii) the hygiene hypothesis proposes alteration of the gut microbiome, with which humans have coevolved, in allergic and autoimmune disease pathogenesis; for example, association of microbiome-altering proton pump inhibitor use with pediatric eosinophilic esophagitis, early-life gastrointestinal infection with celiac disease, and infant antibiotic use and an economically advanced environment with inflammatory bowel disease. Evolutionary perspectives broaden physicians' understanding of disease processes, improve care, and stimulate research.
Subject(s)
Digestive System Diseases , Gastrointestinal Diseases , Helicobacter pylori , Lactose Intolerance , Anti-Bacterial Agents , Biological Evolution , Drug Resistance, Bacterial , Humans , Lactase/genetics , Lactose/metabolism , Lactose Intolerance/geneticsABSTRACT
BACKGROUND: In adulthood the activity of the lactase enzyme is inherited as autosomal dominant form associated to Single nucleotide polymorphisms (SNPs). The present research was aimed to develop a novel genetic method to test lactase non persistence more powerfully. METHODS AND RESULTS: In our study, we selected eight different SNPs that are associated with lactase persistence from Caucasian, Arabian Bedouins, sub-Saharian Africans and Asian populations to set up an approach to detect all the eight different SNPs at the same time in the same sample. This technique is centred on the identification of SNPs with a single nucleotide primer extension method using Sanger sequencing and capillary electrophoresis. CONCLUSIONS: Our method allowed us to check the genotype asset of eight SNPs related to lactase persistence simultaneously and in a very efficient manner. It could be applied to a higher number of SNPs in a single reaction.
Subject(s)
Lactase/deficiency , Lactose Intolerance , Polymorphism, Single Nucleotide , Adult , Female , Humans , Lactase/chemistry , Lactase/genetics , Lactase/metabolism , Lactose Intolerance/enzymology , Lactose Intolerance/genetics , Male , Middle AgedABSTRACT
BACKGROUND: Lactose malabsorption occurs in around 68% of the world's population, causing lactose intolerance (LI) symptoms, such as abdominal pain, bloating, and diarrhea. To alleviate LI, previous studies have mainly focused on strengthening intestinal ß-galactosidase activity while neglecting the inconspicuous drop in the colon pH caused by the fermentation of non-hydrolyzed lactose by the gut microbes. A drop in colon pH will reduce the intestinal ß-galactosidase activity and influence intestinal homeostasis. RESULTS: Here, we synthesized a tri-stable-switch circuit equipped with high ß-galactosidase activity and pH rescue ability. This circuit can switch in functionality between the expression of ß-galactosidase and expression of L-lactate dehydrogenase in response to an intestinal lactose signal and intestinal pH signal, respectively. We confirmed that the circuit functionality was efficient in bacterial cultures at a range of pH levels, and in preventing a drop in pH and ß-galactosidase activity after lactose administration to mice. An impact of the circuit on gut microbiota composition was also indicated. CONCLUSIONS: Due to its ability to flexibly adapt to environmental variation, in particular to stabilize colon pH and maintain ß-galactosidase activity after lactose influx, the tri-stable-switch circuit can serve as a promising prototype for the relief of lactose intolerance.