Evaluation of pharmacokinetics of single-dose primaquine in undernourished versus normally nourished children diagnosed with Plasmodium vivax malaria in Mumbai.

BACKGROUND: The pharmacokinetics of primaquine [PQ] have been the subject of studies in both adults and healthy participants. However, there is no study on its pharmacokinetics in a setting of undernourishment. In India, there is evidence to show considerable malnourishment in children that in turn can affect drug pharmacokinetics. Given that the country is moving towards malaria elimination, the present study was planned with the objective of comparing pharmacokinetics of the drug in undernourished children relative to normally nourished children. MATERIALS AND METHODS: After Institutional Ethics Committee approval, children of either gender between the ages of 5 and 12 years and smear-positive for Plasmodium vivax malaria were included. Nourishment status was determined using the Indian Academy of Pediatrics classification of protein energy malnutrition based on Khadilkar's growth charts. Twelve children each were enrolled in the two groups. PQ was given in the dose of 0.3 mg/kg/d and blood collections were made at 0, 1, 2, 3, 4, 6, 8 and 24 hours post-dosing. Levels were estimated by high-performance liquid chromatography. Chloroquine in the dose of 25 mg/kg was given over three days along with supportive care. RESULTS: Of the 24 children, there were 17 boys and 7 girls. There was a statistically significant difference in the body weight between the undernourished and the normally nourished children [21.5 ± 5.52 vs. 28.8 ± 8.84, P < 0.05]. PQ levels showed wide inter-individual variation in both groups. No significant difference was seen in any pharmacokinetic parameter between the two groups. DISCUSSION: This study adds to the limited body of evidence on the pharmacokinetics of PQ in children with malaria and indicates that the dosing of primaquine could potentially be independent of the nourishment status.

Precision mapping child undernutrition for nearly 600,000 inhabited census villages in India.

There are emerging opportunities to assess health indicators at truly small areas with increasing availability of data geocoded to micro geographic units and advanced modeling techniques. The utility of such fine-grained data can be fully leveraged if linked to local governance units that are accountable for implementation of programs and interventions. We used data from the 2011 Indian Census for village-level demographic and amenities features and the 2016 Indian Demographic and Health Survey in a bias-corrected semisupervised regression framework to predict child anthropometric failures for all villages in India. Of the total geographic variation in predicted child anthropometric failure estimates, 54.2 to 72.3% were attributed to the village level followed by 20.6 to 39.5% to the state level. The mean predicted stunting was 37.9% (SD: 10.1%; IQR: 31.2 to 44.7%), and substantial variation was found across villages ranging from less than 5% for 691 villages to over 70% in 453 villages. Estimates at the village level can potentially shift the paradigm of policy discussion in India by enabling more informed prioritization and precise targeting. The proposed methodology can be adapted and applied to diverse population health indicators, and in other contexts, to reveal spatial heterogeneity at a finer geographic scale and identify local areas with the greatest needs and with direct implications for actions to take place.

Impact of Treatment with RUTF on Plasma Lipid Profiles of Severely Malnourished Pakistani Children.

(1) Background: Little is known on impacts of ready-to-use therapeutic food (RUTF) treatment on lipid metabolism in children with severe acute malnutrition (SAM). (2) Methods: We analyzed glycerophospholipid fatty acids (FA) and polar lipids in plasma of 41 Pakistani children with SAM before and after 3 months of RUTF treatment using gas chromatography and flow-injection analysis tandem mass spectrometry, respectively. Statistical analysis was performed using univariate, multivariate tests and evaluated for the impact of age, sex, breastfeeding status, hemoglobin, and anthropometry. (3) Results: Essential fatty acid (EFA) depletion at baseline was corrected by RUTF treatment which increased EFA. In addition, long-chain polyunsaturated fatty acids (LC-PUFA) and the ratio of arachidonic acid (AA)/linoleic acid increased reflecting greater EFA conversion to LC-PUFA, whereas Mead acid/AA decreased. Among phospholipids, lysophosphatidylcholines (lyso.PC) were most impacted by treatment; in particular, saturated lyso.PC decreased. Higher child age and breastfeeding were associated with great decrease in total saturated FA (ΣSFA) and lesser decrease in monounsaturated FA and total phosphatidylcholines (ΣPC). Conclusions: RUTF treatment improves EFA deficiency in SAM, appears to enhance EFA conversion to biologically active LC-PUFA, and reduces lipolysis reflected in decreased ΣSFA and saturated lyso.PC. Child age and breastfeeding modify treatment-induced changes in ΣSFA and ΣPC.

Metabolic maturation in the first 2 years of life in resource-constrained settings and its association with postnatal growths.

Malnutrition continues to affect the growth and development of millions of children worldwide, and chronic undernutrition has proven to be largely refractory to interventions. Improved understanding of metabolic development in infancy and how it differs in growth-constrained children may provide insights to inform more timely, targeted, and effective interventions. Here, the metabolome of healthy infants was compared to that of growth-constrained infants from three continents over the first 2 years of life to identify metabolic signatures of aging. Predictive models demonstrated that growth-constrained children lag in their metabolic maturity relative to their healthier peers and that metabolic maturity can predict growth 6 months into the future. Our results provide a metabolic framework from which future nutritional programs may be more precisely constructed and evaluated.

The influence of nutrition on clinical outcomes in children with cancer.

Adequate and appropriate nutrition is essential for growth and development in children; all put at risk in those with cancer. Overnutrition and undernutrition at diagnosis raise the risk of increased morbidity and mortality during therapy and beyond. All treatment modalities can jeopardize nutritional status with potentially adverse effects on clinical outcomes. Accurate assessment of nutritional status and nutrient balance is essential, with remedial interventions delivered promptly when required. Children with cancer in low- and middle-income countries (LMICs) are especially disadvantaged with concomitant challenges in the provision of nutritional support. Cost-effective advances in the form of ready-to-use therapeutic foods (RUTF) may offer solutions. Studies in LMICs have defined a critical role for the gut microbiome in the causation of undernutrition in children and have demonstrated a beneficial effect of selected RUTF in redressing the imbalanced microbiota and improving nutritional status. Challenges in high-income countries relate both to concerns about the potential disadvantage of preexisting obesity in those newly diagnosed and to undernutrition identified at diagnosis and during treatment. Much remains to be understood but the prospects are bright for offsetting malnutrition in children with cancer, resulting in enhanced opportunity for healthy survival.

The relevance of nutrition to pediatric oncology: A cancer control perspective.

It is indisputable that adequate and appropriate nutrition is fundamental to the health, growth, and development of infants, children, and adolescents, including those with cancer. Nutrition has a role in most of the accepted components of the cancer control spectrum, from prevention through to palliation. The science of nutrigenomics, nutrigenetics, and bioactive foods (phytochemicals), and how nutrition affects cancer biology and cancer treatment, is growing. Nutritional epigenetics is giving us an understanding that there are possible primary prevention strategies for pediatric cancers, especially during conception and pregnancy, which need to be studied. Primary prevention of cancer in adults, such as colorectal cancer, should commence early in childhood, given the long gestation of nutritionally related cancers. Obesity avoidance is definitely a target for both pediatric and adult cancer prevention, commencing in childhood. There is now compelling evidence that the nutritional status of children with cancer, both overweight and underweight, does affect cancer outcomes. This is a potentially modifiable prognostic factor. Consistent longitudinal nutritional assessment of patients from diagnosis through treatment and long-term follow-up is required so that interventions can be implemented and evaluated. While improving, there remains a dearth of basic and clinical nutritional research in pediatric oncology. The perspective of evaluating nutrition as a cancer control factor is discussed in this article.

Assessment of nutritional status in children with cancer: A narrative review.

A child's appropriate development stems in large part from proper nutrition. Malnutrition is an adverse prognostic factor in children with cancer, and its prevalence is highly variable. Currently, there is no standardized definition and assessment method of nutritional status in pediatric oncology. A complete nutritional assessment includes anthropometry, biochemical, clinical, and dietary assessments. In this article, we explore these methods and suggest practical approaches for pediatric cancer units depending on the levels of care that these can provide. We also advise on the monitoring and follow-up of children with cancer during and after treatment, and discuss potential areas for future research.

Body Composition in Egyptian Children With Transfusion-dependent Thalassemia: The Impact of Nutrition and Metabolic Profile.

BACKGROUND: Growth failure is a common complication in children with beta-thalassemia major (ß-TM) that has persisted despite major treatment advances. It could stem from malnutrition, especially in those who live in poor countries and who have inadequate nutrient intake. AIM: The aim of this study was to assess the influence of nutrition on growth, total body composition, and metabolic profile in Egyptian children with ß-TM. SUBJECTS AND METHODS: This cross-sectional study included 200 children with ß-TM and 50 age-matched and sex-matched healthy children. All subjects underwent full clinical assessment, which included assessment of growth and total body composition using anthropometric measurements (weight, height, mid-arm circumference, skinfold thickness, and body mass index) and bioelectric impedance analysis device (TANITA SC330). Nutritional assessment was performed using 24-hour dietary recall. Fasting serum insulin, C-peptide, and fasting serum lipid profile (high-density lipoprotein, low-density lipoprotein, cholesterol, and triglyceride) were measured. RESULTS: Children with ß-TM had a significantly lower mean value of the daily consumption of the studied nutrient elements including kilocalories, protein, carbohydrate, calcium, and phosphorus (P<0.001). ß-TM had a negative impact on anthropometric measures; the mean of all measurements recorded in children with ß-TM was significantly lower than that in the control group (P<0.001). Children with ß-TM had a significant abnormality in lipid profile, with higher triglyceride levels and lower cholesterol, low-density lipoprotein, and high-density lipoprotein than controls. They had significantly lower serum insulin and C-peptide. Age, sex, serum ferritin, and caloric intake have a significant impact on body composition in children with ß-TM. CONCLUSION: Regular assessment of nutrition is crucial for the health of children with ß-TM.

Decoding the Metabolome and Lipidome of Child Malnutrition by Mass Spectrometric Techniques: Present Status and Future Perspectives.

Child malnutrition (CM) is a global public health problem. It contributes to poor health in one in four children under five years worldwide and causes serious health problems in children, including stunted, wasted, and overweight growth. These serious public health issues lead to a higher chance of living in poverty in adulthood. Malnutrition is related with reduced economic productivity and increases the serious national and international burden. Currently, there is no meaningful therapeutic intervention of CM, and the use of different therapeutic foods has shown poor outcomes among supplemented malnourished children. The role of metabolites and lipids has been extensively recognized as early determinants of child health, but their contribution in CM and its pathobiology are poorly understood. This perspective provides a most recent update on these aspects. After briefly introducing the disciplines of metabolomics and lipidomics, we describe a mass spectrometry-based metabolic workflow for analysis of both metabolites and lipids and summarize several recent applications of metabolomics and lipidomics in CM. Finally, we discuss the future directions of the field toward the development of meaningful interventions for CM through metabolomics and lipidomics advances.

Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.

: Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.

Effects of microbiota-directed foods in gnotobiotic animals and undernourished children.

To examine the contributions of impaired gut microbial community development to childhood undernutrition, we combined metabolomic and proteomic analyses of plasma samples with metagenomic analyses of fecal samples to characterize the biological state of Bangladeshi children with severe acute malnutrition (SAM) as they transitioned, after standard treatment, to moderate acute malnutrition (MAM) with persistent microbiota immaturity. Host and microbial effects of microbiota-directed complementary food (MDCF) prototypes targeting weaning-phase bacterial taxa underrepresented in SAM and MAM microbiota were characterized in gnotobiotic mice and gnotobiotic piglets colonized with age- and growth-discriminatory bacteria. A randomized, double-blind controlled feeding study identified a lead MDCF that changes the abundances of targeted bacteria and increases plasma biomarkers and mediators of growth, bone formation, neurodevelopment, and immune function in children with MAM.

Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus-infected children in relation to treatment outcomes.

AIMS: Describe the pharmacokinetics (PK) of the antiretroviral drugs abacavir and lamivudine in malnourished paediatric patients and relate to viral load outcomes after 12 and 48 weeks of treatment. METHODS: Severely malnourished human immunodeficiency virus-infected children were randomized to early (within 14 days) or delayed (after nutritional recovery) initiation of antiretroviral treatment (ART) using World Health Organization weight-band dosages. Abacavir and lamivudine concentrations were measured as a secondary objective on day 1 and day 14 and patients were followed-up to week 48. Population PK of abacavir and lamivudine were described using NONMEM. RESULTS: In total, 623 abacavir and 627 lamivudine concentrations were collected from 75 paediatric patients aged 0.1-10.8 (median 1.4) years. Abacavir PK was described by a 2-compartment model, patients randomized to early ART showed increased bioavailability of 31%. Apparent clearance (CL/F, L/h/7 kg) of abacavir increased from day 1 to day 14 from 3.33 (95% confidence interval 2.71-4.12) to 5.86 (95% confidence interval 4.78-7.3). A 1-compartment model described lamivudine PK, variability on CL/F was explained by maturation with age, with age at half-matured CL/F being 4 months. For both drugs allometrically scaled total body weight was related to CL/F and apparent volume of distribution. PK exposure did not correlate with virological outcomes or death at 12 or 48 weeks. CONCLUSION: Increases in Abacavir's CL/F between day 1 to day 14, bioavailability and PK variability with early start of ART was found in this cohort of severely malnourished children; however, these changes did not influence virological outcomes. The study supports the use of weight-band dosage tables.

Gut microbiota alterations and dietary modulation in childhood malnutrition - The role of short chain fatty acids.

The gut microbiome affects the health status of the host through different mechanisms and is associated with a wide variety of diseases. Both childhood undernutrition and obesity are linked to alterations in composition and functionality of the gut microbiome. One of the possible mechanisms underlying the interplay between microbiota and host metabolism is through appetite-regulating hormones (including leptin, ghrelin, glucagon-like peptide-1). Short chain fatty acids, the end product of bacterial fermentation of non-digestible carbohydrates, might be able to alter energy harvest and metabolism through enteroendocrine cell signaling, adipogenesis and insulin-like growth factor-1 production. Elucidating these mechanisms may lead to development of new modulation practices of the gut microbiota as a potential prevention and treatment strategy for childhood malnutrition. The present overview will briefly outline the gut microbiota development in the early life, gut microbiota alterations in childhood undernutrition and obesity, and whether this relationship is causal. Further we will discuss possible underlying mechanisms in relation to the gut-brain axis and short chain fatty acids, and the potential of probiotics, prebiotics and synbiotics for modulating the gut microbiota during childhood as a prevention and treatment strategy against undernutrition and obesity.

Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children.

The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.

Determinant Variables, Enteric Pathogen Burden, Gut Function and Immune-related Inflammatory Biomarkers Associated With Childhood Malnutrition: A Prospective Case-Control Study in Northeastern Brazil.

Malnutrition results in serious consequences for growth and cognitive development in children. We studied select child and maternal biologic factors, socioeconomic factors, enteric pathogenic burden and gut function biomarkers in 402 children 6-24 months of age in Northeastern Brazil. In this prospective case-control study, not being fed colostrum [odds ratio (OR): 3.29, 95% confidence interval (CI): 1.73-6.26], maternal age ≥18 years (OR: 1.88, 95% CI: 1.10-3.22) and no electric fan (OR: 2.46, 95% CI: 1.22-4.96) or bicycle (OR: 1.80, 95% CI: 1.10-2.95) in the household were positively associated, and higher birth weight (OR: 0.27, 95% CI: 0.19-0.38), larger head circumference (OR: 0.74, 95% CI: 0.66-0.82) and shortness of breath in the last 2 weeks (OR: 0.49, 95% CI: 0.27-0.90) were negatively associated with malnutrition. Subclinical enteric pathogen infections were common, and enteroaggregative Escherichia coli infections were more prevalent in malnourished children (P = 0.045). Biomarkers such as the lactulose-mannitol test, myeloperoxidase, neopterin and calprotectin were highly elevated in both malnourished and nourished children. Nourished children had a better systemic immune response than the malnourished children, as detected by elevated serum amyloid A-1 and soluble cluster of differentiation protein 14 biomarkers (P < 0.001). Serum amyloid A-1 and soluble cluster of differentiation protein 14 were also associated with better nutritional Z scores. Neonatal, maternal and socioeconomic factors were associated with malnutrition in children. There was a substantial subclinical enteric pathogen burden, particularly with enteroaggregative E. coli, in malnourished children.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

BACKGROUND: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. OBJECTIVES: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. METHODS: We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. RESULTS: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. CONCLUSIONS: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

Evaluation of pharmacokinetics of single-dose chloroquine in malnourished children with malaria- a comparative study with normally nourished children.

OBJECTIVES: Studies on antimalarial kinetics in children or adults who are undernourished or malnourished are both limited and have yielded conflicting results. The present study was carried out with the objectives of evaluating the pharmacokinetics of single dose chloroquine and its metabolite desethylchloroquine in children who were undernourished and compare them with children who were normally nourished. METHODS: Children of either gender between the ages of 5 and 12 years, smear positive for P. vivax malaria and classified either as well nourished or undernourished were included. Undernourishment was adjudged based on the Indian Academy of Pediatrics (IAP) classification of protein energy malnutrition [PEM] which in turn was based on Khadilkar's growth charts. All participants received 10 mg/kg on the first day followed by 10 mg/kg on Day 2 and 5 mg/kg on Day 3 along with supportive treatment. Blood samples for the levels of chloroquine [CQ] and desethylchloroquine [DECQ] were collected at 0, 0.5, 1, 2 4, 8, 12, 24, 48, 72 hours and 14 days after the first dose and levels assessed by High Performance Liquid Chromatography. RESULTS: A total of 12 children who were normally nourished and 13 who were undernourished were studied. Wide inter-individual variability was seen in the levels of both drug and metabolite in both groups of patients. However, the differences in Cmax, AUC 0-inf, Clearance, half life and Vd between the two groups were not significantly different. DISCUSSION: Our results indicate that dosage requirement is unlikely to be needed for chloroquine in undernourished children with uncomplicated P. vivax malaria.

Protein Quality and Growth in Malnourished Children.

BACKGROUND: Protein quality refers to the amounts and ratios of essential amino acids in a food. Two methods most commonly used for determining protein quality are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensible amino acid score (DIAAS). OBJECTIVE: To use existing literature to compare different amino acid profiles and PDCAAS and DIAAS scores in individuals with acute inflammation and to assess their relationship with weight gain in children with severe acute malnourished (SAM). METHODS: A series stable isotope studies were previously conducted in children with SAM and acute infection, and these data were reviewed with respect to protein synthesis. Eleven published treatment trials for SAM with different therapeutic foods were analyzed to examine the relationship between protein quality scores with weight gain (g/kg/d). Protein scores were calculated with the PDCAAS and DIAAS amino acid reference patterns. A DIAAS score adjusted for the higher weight gain expected in malnourished children was also used. Bivariate correlation analysis was used to examine this relationship. RESULTS: The protein kinetic data supported the hypothesis that a balance of amino acids that matches the composition of acute-phase proteins maximizes amino acid synthesis. Protein quality scores were highly correlated with the rate of weight gain in recovery from SAM, and the DIAAS scoring system adjusted for the higher expected weight gain had the strongest correlation with the observed weight gain. CONCLUSION: Protein quality scores must account for physiologic status so that they better match with needs and thus better promote health.

Progressive Changes in the Plasma Metabolome during Malnutrition in Juvenile Pigs.

Severe acute malnutrition (SAM) is one of the leading nutrition-related causes of death in children under five years of age. The clinical features of SAM are well documented, but a comprehensive understanding of the development from a normal physiological state to SAM is lacking. Characterizing the temporal metabolomic change may help to understand the disease progression and to define nutritional rehabilitation strategies. Using a piglet model we hypothesized that a progressing degree of malnutrition induces marked plasma metabolite changes. Four-week-old weaned pigs were fed a nutrient-deficient maize diet (MAL) or nutritionally optimized reference diet (REF) for 7 weeks. Plasma collected weekly was subjected to LC-MS for a nontargeted profiling of metabolites with abundance differentiation. The MAL pigs showed markedly reduced body-weight gain and lean-mass proportion relative to the REF pigs. Levels of eight essential and four nonessential amino acids showed a time-dependent deviation in the MAL pigs from that in the REF. Choline metabolites and gut microbiomic metabolites generally showed higher abundance in the MAL pigs. The results demonstrated that young malnourished pigs had a profoundly perturbed metabolism, and this provides basic knowledge about metabolic changes during malnourishment, which may be of help in designing targeted therapeutic foods for refeeding malnourished children.

Epigenetics in Paediatric Gastroenterology, Hepatology, and Nutrition: Present Trends and Future Perspectives.

Epigenetics can be defined as stable, potentially heritable changes in the cellular phenotype caused by mechanisms other than alterations to the underlying DNA sequence. As such, any observed phenotypic changes including organ development, aging, and the occurrence of disease could be driven by epigenetic mechanisms in the presence of stable cellular DNA sequences. Indeed, with the exception of rare mutations, the human genome-sequence has remained remarkably stable over the past centuries. In contrast, substantial changes to our environment as part of our modern life style have not only led to a significant reduction of certain infectious diseases but also seen the exponential increase in complex traits including obesity and multifactorial diseases such as autoimmune disorders. It is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment, and a large body of existing evidence supports the importance of environmental factors such as diet and nutrition, infections, and exposure to toxins on human health. This seems to be particularly the case during vulnerable periods of human development such as pregnancy and early life. Importantly, as the first point of contact for many of such environmental factors including nutrition, the digestive system is being increasingly linked to a number of "modern" pathologies. In this review article, we aim to give a brief introduction to the basic molecular principals of epigenetics and provide a concise summary of the existing evidence for the role of epigenetic mechanisms in gastrointestinal health and disease, hepatology, and nutrition.