Abstract

The study of epigenetics dates back to the early 1940s when Conrad Waddington, a British developmental biologist, first coined the term “epigenetics” to describe the interaction between genes and their environment during development. Waddington proposed the concept of the “epigenetic landscape,” which depicted how gene expression could be influenced by external factors.

In the decades that followed, researchers began to unravel the intricacies of epigenetic mechanisms and their impact on gene regulation. The discovery of DNA methylation and histone modification provided insights into how environmental factors, such as diet, could affect gene expression patterns without altering the underlying genetic code.

Thus, after many years of research, epigenetics can be defined as the study of how behaviours and environmental factors can cause changes to your epigenome, without altering the genome. This research article explores the intricate relationship between epigenetics and diet on future generations, emphasising how environmental factors impact metabolic processes and disease susceptibility.

Furthermore, this essay delves into the transgenerational impacts of a high-fat/sugar diet, a nutrient-deficient diet, and a change in gut microbiota in order to highlight what the average human diet should look like. By describing these pathways, this paper aims to underscore the importance of a specific diet and suggest ways to mitigate the adverse effects of diet-induced epigenetic alterations. Therefore, this article establishes the need for further research and calls attention to the issue of epigenetics and diet from a public health perspective.

Research on Epigenetics

The role of genetic background in determining dietary responses within a community is widely acknowledged. However, recent scientific evidence suggests that it is not solely genetic factors, but rather a complex interplay between environmental factors and genetic background, that ultimately governs diet-gene interactions (Kaput, J., 2004). A 2012 study also documented the impact of poor nutrition on the long-term health of offspring, as well as the susceptibility to chronic diseases later in life (Koletzko, B. et al, 2012). Despite this, little is currently understood about the molecular processes that initiate the development of food intake-related pathologies (Georgel, P.T. et al, 2021). Traditionally, the molecular bacteriology of diseases has been focused on understanding the genetic implications of specific pathogens. However, advancements in epigenetic research, such as the development of AI models to predict the DNA outcome in future generations, have prompted scientists to reevaluate how DNA modifications influenced by different diets enable the body to respond to food intake and establish alternate pathogen defence mechanisms (Hamamoto et al., 2019). New gene sequencing technologies have also played a crucial role in identifying genetic variations and their association with various dietary patterns. Furthermore, scientists have begun to explore the influence of epigenetic factors and dietary components on epigenetic changes. Particularly, researchers have started to investigate the gene outcomes resulting from diet-gene interactions in response to environmental factors such as dietary ingredients, such as fatty acids, altering the composition of intestinal bacteria.

Diet on Epigenetics

There is a wide range of evidence that suggests environmental stressors, such as diet, can have an impact across multiple generations (Lumey et al., 2009). For example, a 2009 article revealed that descendants of individuals who experienced starvation during the Netherlands “hunger winter” were at a higher risk for diabetes (Ramirez et al., 2022). Nevertheless, the cause-and-effect relationship of this type of inheritance remained uncertain. Epigenetics plays a crucial role in understanding how various lifestyle factors, such as dietary choices, can impact future generations. Epigenetics focuses on investigating changes in organisms that are caused by modifications in gene expression rather than alterations in the genetic code itself. It examines the factors and processes that influence whether genes are switched on or off, as well as the factors that control cell differentiation. These factors encompass aspects of lifestyle, exposure to the environment, and nutrition (Zhang. et al., 2021). In essence, studying epigenetics helps establish molecular connections between our physical well-being and the decisions we make in our lives, including the wide variety of foods and beverages consumed by humans.

Epigenetics effects on Inheritance

Epigenetics is a field within life science that has gained significant attention in recent years due to its potential for enhancing our understanding of the human body and discovering new approaches to developing therapeutic and diagnostic products for various conditions (Ashe. et al., 2021). The term is closely associated with examining the causes of changes in gene expressions within the human body and how these changes can be inherited across generations. Epigenetic research is not limited to studying temporary or heritable gene expression changes specific to the germline, but is also crucial for comprehending genetics as a whole and how gene regulation is influenced by the cellular environment. This knowledge is relevant regardless of whether we are examining transient or permanent cell differentiation. Epigenetics has provided a valuable connection between genetic markers and many medical conditions, such as Peutz-Jegher syndrome, which involves tumour formation in the digestive system and inherited susceptibility to certain cancers (Ilango et al., 2020). In today’s medical practice, hermeneutics (the study of human emotions in medical terms) and subsequent clinical diagnosis are becoming increasingly integrated, marking a significant shift.

Importance of analysing Epigenetic Modifications of different diets

The analysis of epigenetic modifications resulting from dietary choices can provide valuable insights into the potential impact on future generations’ health. A deeper understanding of this phenomenon could also aid in developing more customised dietary interventions that can effectively manage the adverse effects of diet-induced epigenetic modifications on health. This is especially crucial for individuals who have poor-quality diets, as their choices can have consequences not only for their own health, but also for the health of future generations.

Of particular importance, however, are the observations of potential “nutritional reprogramming,” where an unhealthy maternal diet can lead to increased disease susceptibility in offspring later in life (Haggartyet al., 2013). It is also worth considering the epigenomic effects of different diets on both males and females, as evidence suggests that paternal diet can also play a role. For instance, a study by Wen et al. (2018) explored the sex-specific effects of paternal high-fat diets on offspring growth, metabolic phenotypes, and epigenetic changes and found that there is a difference in epigenetic effects of unhealthy diets on males and females (Wen et al., 2018).

However, the research in this area has been limited, particularly regarding the effects of paternal diets, especially high-fat diets, on epigenetic outcomes and their potential implications for therapeutic processes like in-vitro fertilisation (IVF). Furthermore, understanding diet-induced epigenetic changes can also shed light on the mechanisms of natural selection. It can help explain why certain genetic polymorphisms have survived evolution, whether it be due to the mutations themselves or the resulting changes in methylation patterns that provide survival advantages until reproductive age or even later when the negative effects are offset by the inability to adapt to other environmental triggers. This knowledge has significant implications for the fields of anthropology (the study of human societies), the understanding of current genetic diversity, and the ability to adapt to other environmental triggers.

The Difficulty of Tracing Epigenetic Inheritance

While transgenerational epigenetic inheritance is a widely studied field, the complete validity of epigenetic marks being passed down to future generations is questioned. The inability to control genetic, ecological, and cultural factors undermine the establishment of causal links between epigenetics and phenotypes of future generations (Horsthemke, 2018). It is acknowledged that transgenerational effects occur in mammals, but it is not certain how much these environmental effects can be passed on without the initial stimuli. In mammals, germline reprogramming is efficient and it is unlikely that these two marks of epigenetic erasure will lead to epigenetic marks being passed on (Heard et al., 2014). Thus, it can not be proven that transgenerational phenotypes and epigenetics have a cause-and-effect relationship.

The Impact of High Fat and Sugar Diets

Dr. Oliver J. Rando, a molecular biologist at the University of Massachusetts Medical School, has focused years of research on how dietary factors, such as high fat and sugar intake, can alter epigenetic markers in the liver and other tissues. These studies have shown that high fat and sugar diets can induce epigenetic changes that contribute to obesity, diabetes, and other metabolic disorders. Similarly, excessive consumption of saturated fats has been linked to alterations in DNA methylation patterns, which can disrupt “normal” gene expression in adipose (connective) tissue and promote fat storage (Perfilyev et al., 2017).

In addition, high sugar intake has been shown to affect histone modification patterns, leading to changes in gene expression that contribute to insulin resistance and inflammation. These epigenetic alterations can have lasting effects on metabolic health and increase the risk of chronic diseases.

Dr. Robert H. Lustig, a paediatric endocrinologist at the University of California, San Francisco, has been a vocal advocate for reducing sugar consumption to improve metabolic health (Lustig , 2010). Dr. Lustig’s research has highlighted the role of fructose in promoting insulin resistance and liver disease through epigenetic mechanisms, contributing to negative metabolism diseases.

Another instance is Dr. Tanya C. Sippy, a nutritional scientist at the University of North Carolina, who has conducted pioneering research on the effects of high fat diets on epigenetic regulation in the brain specifically (Sippy et al., 2021). Her work has shown that saturated fats can alter histone acetylation patterns in the hippocampus, a part of the brain that contributes to memory, learning, and emotion, leading to cognitive impairments and mood disorders.

Perspectives and Analysis

From a positive perspective, the study of high fat and sugar diets on epigenetics has shed light on the importance of nutrition in gene regulation and metabolic health. Research, such as the ones listed above, have provided new insights into the mechanisms underlying obesity and diabetes, paving the way for targeted interventions to improve public health.

However, there are also negative implications of this research, as it highlights the potential harm of unhealthy dietary habits on epigenetic regulation and disease risk. The prevalence of high fat and sugar diets in modern society has fueled an epidemic of metabolic disorders, underscoring the urgent need for dietary interventions and policy changes to promote healthier eating habits.

Future Developments

Looking ahead, future research in the field of epigenetics and nutrition is likely to focus on personalised dietary recommendations based on individual genetic and epigenetic profiles. This approach, known as “precision nutrition”, aims to optimise health outcomes by tailoring dietary interventions to an individual’s unique genetic makeup and epigenetic signatures.

Advances in technology, such as high-throughput sequencing and bioinformatic tools, have made it possible to analyse epigenetic markers on a genome-wide scale and identify novel targets for therapeutic intervention. This research holds promise for the development of precision medicine approaches to prevent and treat metabolic disorders associated with high fat and sugar diets.

Nutrient deficiencies

Nutrient deficiencies can have a profound effect on epigenetics, which refers to changes in gene expression that are not caused by alterations in the DNA sequence. These changes can have significant impacts on an individual’s health, well-being, and can even be passed down to future generations. In this section, we will explore the relationship between nutrient deficiencies and epigenetics, and how this connection can have far-reaching consequences for human health.

To understand how nutrient deficiencies affect epigenetics, we must first understand the role of nutrients in the body. Nutrients are essential substances that our bodies need to function properly. They are obtained from the food we eat and are responsible for a wide range of biological processes, including energy production, cell growth and repair, and hormone regulation. Without adequate levels of nutrients, our bodies cannot carry out these processes effectively, leading to a host of health issues.

One of the key ways that nutrient deficiencies can impact epigenetics is through the production of methyl groups. Methyl groups are small molecules that attach to our DNA and act as a “switch” that turns genes on or off. This process is known as DNA methylation and is crucial for regulating gene expression. However, when our bodies lack certain nutrients, such as folate, vitamin B12, and choline, the production of methyl groups can be disrupted, leading to changes in gene expression (Zeisel., 2017).

In fact, folate deficiency can lead to alterations in DNA methylation patterns, particularly in genes involved in brain development and function (Irwin et al., 2016). This can have long-term effects on cognitive function and mental health. Similarly, deficiencies in vitamin B12 and choline have been linked to changes in DNA methylation that can affect the risk of chronic diseases, including cardiovascular disease and cancer.

In addition to affecting DNA methylation, nutrient deficiencies can also impact another important epigenetic process known as histone modification (Milagro et al., 2013). Histones are proteins that help package and organise our DNA within the cell. Like DNA methylation, histone modifications can influence gene expression, and nutrient deficiencies have been shown to disrupt this process. For instance, a deficiency in zinc, an essential mineral, can lead to changes in histone acetylation, which can affect the expression of genes involved in immune function and inflammation (Brito et al., 2020).

Furthermore, nutrient deficiencies can also influence the activity of microRNAs, small molecules that regulate gene expression by binding to specific sequences in the RNA. These microRNAs play a crucial role in various biological processes, including cell growth and differentiation, and their dysregulation has been linked to several diseases. Research has shown that deficiencies in nutrients such as vitamin D, selenium, and iron can alter the production and activity of microRNAs, leading to changes in gene expression (Beckett et al., 2020).

The effects of nutrient deficiencies on epigenetics are not limited to the individual experiencing the deficiency. It turns out that these changes can be passed down to future generations through a process known as transgenerational epigenetic inheritance. This means that the offspring of individuals who have experienced nutrient deficiencies may also be at risk of developing health issues due to altered gene expression.

Role of gut microbiota on adapting epigenetics

The gut microbiota, also known as gut flora or gut bacteria, refers to the community of microorganisms that reside in our digestive tract, mainly in the colon, as part of a complex ecosystem that consists of trillions of microorganisms (Billah., 2022). These microorganisms have a symbiotic relationship with our bodies, where they provide essential functions such as breaking down food, producing vitamins, and protecting against harmful pathogens. However, a recent study by Wen et al. in 2018 shows that the gut microbiota also has a significant impact on our epigenetics, influencing various physiological processes such as digestion, metabolism, and immunity.

One of the ways in which gut microbiota influence epigenetics is through the production of metabolites. Metabolites are small molecules that are produced by the gut microbiota during the digestion process (Shi and Qi ., 2023). These molecules can enter our bloodstream and travel to different organs, including the brain, where they can influence gene expression. For example, a metabolite called butyrate, which is produced by gut bacteria, has been found to have anti-inflammatory properties and can regulate the expression of genes involved in inflammation (Pannaraj et al., 2017). This can have a significant impact on diseases such as inflammatory bowel disease, where chronic inflammation is a key factor.

Furthermore, gut microbiota can also influence the production of short-chain fatty acids (SCFAs), which are another type of metabolite (Portincasa et al., 2022). SCFAs are produced when gut bacteria ferment dietary fibre, and they have been shown to have a wide range of effects on our body. One of the most significant effects of SCFAs is their ability to regulate the expression of genes involved in energy metabolism. This means that the gut microbiota can play a role in conditions such as obesity and type 2 diabetes, where dysregulation of energy metabolism is a key factor.

In addition to metabolites, gut microbiota can also directly affect epigenetic mechanisms. One such mechanism is DNA methylation. For example, a study by Bhat and Kapila (2017) revealed that certain gut bacteria can produce enzymes that can alter the methylation pattern of our DNA , which can have long-lasting effects on gene expression and potentially lead to the development of diseases (Bhat and Kapila., 2017).

Moreover, the gut microbiota is not only influenced by our diet and lifestyle, but it can also be affected by external factors such as antibiotics, stress, and pollution. These factors can disrupt the balance of our gut microbiota, leading to dysbiosis, which refers to an imbalance of the gut bacteria. Dysbiosis has been linked to various diseases and can also affect epigenetic mechanisms, further emphasising the crucial role of gut microbiota in our health.

To summarise, the gut microbiota plays a significant role in adapting epigenetics, which can have a profound impact on our health. The production of metabolites, direct influence on epigenetic mechanisms, and susceptibility to external factors all contribute to the complex relationship between gut microbiota and our epigenetics.

How obesity related diets affect the future generations

The gut microbiome and immune system co-develop around the time of birth, well after genetic information has been passed from the parents to the offspring. Each of these ‘organ systems’ displays plasticity. Despite this plasticity, there is a growing appreciation that these ‘organ systems’ once established, are remarkably stable. For example, the immune system rapidly mounts responses to infections, and once cleared, resolves inflammatory responses to return to homeostasis. However, a skewed immune system, caused by the effects of obesity, does not easily return to homeostasis. As previously covered, gut microbiota is affected by changes in the environment, and dysbiotic gut microbiota can be developed through poor diet and sedentary lifestyle. Recent observations suggest that maternal factors encountered both in utero and after birth can directly or indirectly impact the development of the offspring’s gut microbiome and immune system (Romano-Keeler and Weitkamp., 2015). This shows how non-genetic maternal influences can have long term effects on the offspring’s health. How and when the microbes comprising the gut microbiota of the offspring are acquired, and how this community becomes assembled, are not well understood. At the time of delivery, babies become exposed to a plethora of microbes. The microbes encountered are at least partially dependent upon delivery mode. Vaginally delivered babies have microbial communities similar to their mother’s vaginal microbiota, and caesarian section delivered babies having microbial communities similar to those of their mother’s skin. Moreover, breastmilk may contribute to the offspring’s developing gut microbiota beyond providing a nutrient source for microbes (Edouard Bourre and Marc Paquotte., 2008). The breast milk microbiome is composed of bacteria commonly seen on the skin and within the gastrointestinal tract (Bar-Yoseph et al., 2023). Therefore, indicating that some dysbiotic gut microbiota may be inherited.

Diet approach

Various diet approaches can be investigated in order to see which is the most effective way to restore the balance of gut microbiota in the parents so as to prevent transgenerational inheritance of these microbiomes (Rosenberg. and Zilber-Rosenberg., 2021). The Mediterranean and Atlantic diets are both considered to preserve a good health status. The Mediterranean diet is an assortment of habitual eating behaviours followed by people in the countries contiguous to the Mediterranean Sea. Significant protection from chronic degenerative diseases has been provided by observing the Mediterranean diet. The Atlantic diet has been associated with metabolic health and lower mortality from coronary diseases and some cancers. The three components of the Atlantic diet include vitamin B, omega 3 fatty acids, and iodine, which may bring health benefits to consumers in the Atlantic area (Edouard Bourre, and Marc Paquotte., 2008). Diet has an immediate impact on microbiota composition. This can be synthetically described in terms of an increase or decrease in representative groups of species, as well as of a significant modification in the metabolites released in the environment.

Diet adjustment is a very easy and safe therapeutic strategy. Furthermore, when adopting a dietary approach, the contribution of micronutrients should be considered as an important factor influencing gut microbiota composition. Micronutrients, such as zinc, vitamins D/A, and folate deficiencies in early life may influence the maturation of the gut microbiota and its interaction with the host (Bar-Yoseph et al., 2023), with effects in adolescence and adult life. Additional information about gut micronutrient synthesis and its impact on microbiota composition and functions is necessary to improve the current understanding of the role of micronutrients. Studies investigating the impact of the microbiota on obesity and other pathologies should take into account the impact of micronutrient deficits (Cani et al., 2011). Hence, in a diet approach to rebuild the gut microbiota, there must be prior knowledge of the type of dysbiosis to establish personalised treatments. Metabolic profiling technologies provide valid support for the improvement of functional foods. The existence of high inter-individual variability indicates that a more personalised approach, accompanied by personalised functional foods, is the way forward as diet adjustment is a very easy and safe therapeutic strategy.

High-fat diet effect on pregnant mice offspring

Research has shown that eating a diet heavy in fat and low in fibre, which is a notable pattern of eating behaviour in the general American population, disrupts the gut microbiome’s bacterial equilibrium (Zmora. et al., 2019). As previously mentioned, the digestive system’s resident population of beneficial and dangerous bacteria is known as the microbiome. An increasing amount of research indicates that a high-fat diet consumed by the mother during pregnancy may increase the risk of health issues in the foetus. These problems range from neurodevelopmental diseases, which may vary from autism spectrum disorder to metabolic disorders, such as obesity (Matz et al., 2023).

In Shelly A. Buffington’s experiment, pregnant mice were categorised into two groups: one group was provided with a high-fat diet, while the other group was given a conventional diet. The study revealed that pregnant mice following a high-fat diet displayed imbalances in their intestinal microbes in comparison to those following a standard diet (Matz et al., 2023). More precisely, the high-fat diet modified the arrangement and variety of bacteria in the gastrointestinal tract.

Moreover, the study investigated the behavioural consequences in the offspring of these mice. Interestingly, children of mice that were given the high-fat diet exhibited a change in social behaviour in comparison to the offspring of mothers on the regular diet. The observed abnormalities in gut microbiota resulting from a high-fat diet in mothers had a lasting impact on the behaviour of their offspring, extending to numerous generations (Matz. et al., 2023).

The findings emphasise the possible enduring effects of parental dietary decisions on the health and behaviour of children. They emphasise the significance of maternal nutrition in influencing the gut microbiome of offspring and propose a connection between changes in gut microbiota and social behaviour. This study enhances our comprehension of the intricate relationship between nutrition, gut microbiota, and behaviour, and its potential impact on public health and dietary guidelines for pregnant women.

Use of CRISPR/Cas9

Epigenetic marks, such as methylation or acetylation, at specific genomic loci and histone residues can either be inherited or acquired, and can influence gene expression. Recent studies have used CRISPR/Cas9 genome editing to investigate the roles and targets for these epigenetic marks (Chao et al., 2011). In one such study, researchers performed CRISPR-mediated knockout of all three active DNA methyltransferases present in human embryonic stem cells, to characterise viable, pluripotent cell lines and study the distinct effects on the DNA methylation landscape (Doudna et al., 2011). But researchers increasingly need methods to introduce epigenetic modifications at desired genomic loci, in order to model diseases such as obesity and test hypotheses regarding potential therapeutic strategies. Using the CRISPR/Cas9 system, epigenetic editing has now become feasible. Utilising inactive dCas9 as a DNA-binding domain platform, fused enzymes such as DNA methylases, histone acetyltransferases, and deacetylases, can be targeted to alter the epigenetic state at precise locations within the genome. Researchers have used this approach to fuse the catalytic core of human acetyltransferase p300 with dCas9. This has proven to be sufficient for acetylation of histone H3 lysine 27 at specific target sites and to robustly activate transcription of target genes. Cas9 epigenetic effectors (epiCas9s) can also be used for genome-wide screening to discover novel relationships between epigenetic modifications, chromatin states, and phenotypes such as cellular differentiation or disease progression.

Poor Nutrition Effects on Low-Income Communities

While a sustainable diet is crucial for the health and wellbeing of future generations in terms of transgenerational epigenetic inheritance, suffice it to note that some people in low-income communities or families lack access to foods with great health benefits and turn to foods with too much sodium, fat, and sugar (de Araújo et al., 2022). Overconsumption of these nutrients increases people’s risk of developing chronic diseases such as heart disease, type 2 diabetes mellitus, and some types of cancers. Due to expensive fruits and vegetables, lack of transportation, and other factors, people in low-income communities do not consume the recommended servings of fruits and vegetables according to the Dietary Guidelines (Chun et al, 2022). As stated previously, there is a strong link between epigenetics and the human diet. Thus, there is a risk of unhealthy food consumption leading to modified epigenetic marks that could be passed down to future generations, impacting their subsequent health and quality of life. Overall, this accessible diet that contains artificial and unhealthy additives could take a massive toll on the general health of humans in a community through generations. There must be modifications to the food industry to prioritise a more sustainable, convenient diet that all communities can access (Capone et al., 2014). In conclusion, negative effects of transgenerational epigenetic inheritance in regard to diet might have greater impacts on low-income communities, who have limited access to foods with greater health benefits due to affordability.

Conclusion

In conclusion, this comprehensive exploration highlights the critical role of diet in shaping epigenetic processes and influencing health outcomes across generations. These findings highlight the complex interplay between dietary choices, epigenetic modification, and gut microbiota, underscoring the importance of a balanced diet for optimal health. Therefore, understanding how diet-induced epigenetic changes can be transmitted across generations opens paths for personalised dietary interventions and preventive plans to mitigate the long-term health consequences of poor dietary habits. Further research is warranted to elucidate the underlying mechanisms and develop targeted interventions to promote healthy gene expression patterns and prevent the transmission of adverse health outcomes through epigenetic inheritance. By unravelling the complexities of diet-gene interactions, we can set a precedent for more effective public health initiatives and personalised interventions to improve the health and well-being of present and future generations.

Ashe, A., Colot, V. and Oldroyd, B.P., 2021. How does epigenetics influence the course of evolution?. Philosophical transactions of the Royal Society B, 376(1826), p.20200111. 

Beckett, E.L., Yates, Z., Veysey, M., Duesing, K. and Lucock, M., 2014. The role of vitamins and minerals in modulating the expression of microRNA. Nutrition research reviews, 27(1), pp.94-106.

Brito, S., Lee, M.G., Bin, B.H. and Lee, J.S., 2020. Zinc and its transporters in epigenetics. Molecules and cells, 43(4), pp.323-330.

Bhat, M.I. and Kapila, R., 2017. Dietary metabolites derived from gut microbiota: critical modulators of epigenetic changes in mammals. Nutrition reviews, 75(5), pp.374-389.

Capone, R., Bilali, H.E., Debs, P., Cardone, G. and Driouech, N., 2014. Food system sustainability and food security: connecting the dots. Journal of Food Security, 2(1), pp.13-22.

De Araújo, J.R.T., Ferreira, L.M.D.B.M., Jerez-Roig, J. and de Lima, K.C., 2022. Mobility limitation in older adults residing in nursing homes in Brazil associated with advanced age and poor nutritional status: an observational study. Journal of Geriatric Physical Therapy, 45(3), pp.E137-E144.

Deltcheva, E., Chylinski, K., Sharma, C.M., Gonzales, K., Chao, Y., Pirzada, Z.A., Eckert, M.R., Vogel, J. and Charpentier, E., 2011. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature, 471(7340), pp.602-607.

Delzenne, N.M., Neyrinck, A.M. and Cani, P.D., 2011. Modulation of the gut microbiota by nutrients with prebiotic properties: consequences for host health in the context of obesity and metabolic syndrome. Microbial cell factories, 10, pp.1-11.

Edouard Bourre, J.M. and Marc Paquotte, P., 2008. Contributions (in 2005) of marine and fresh water products (finfish and shellfish, seafood, wild and farmed) to the French dietary intakes of vitamins D and B12, selenium, iodine and docosahexaenoic acid: impact on public health. International journal of food sciences and nutrition, 59(6), pp.491-501.

Elce, A., Amato, F., Zarrilli, F., Calignano, A., Troncone, R., Castaldo, G. and Canani, R.B., 2017. Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells. Beneficial Microbes, 8(5), pp.841-847.

Georgel, P.T. and Georgel, P., 2021. Where epigenetics meets food intake: their interaction in the development/severity of gout and therapeutic perspectives. Frontiers in Immunology, 12, p.752359.

Hamamoto, R., Komatsu, M., Takasawa, K., Asada, K. and Kaneko, S., 2019. Epigenetics analysis and integrated analysis of multiomics data, including epigenetic data, using artificial intelligence in the era of precision medicine. Biomolecules, 10(1), p.62.

Haggarty, P., Ferguson-Smith, A.C., Kuh, D., Cooper, R., Hardy, R., Richards, M. and Ben-Shlomo, I., 2013. Life course epigenetics and healthy ageing. A life course approach to healthy ageing, pp.198-212.

Heard E, Martienssen RA (2014). Transgenerational epigenetic inheritance: myths and mechanisms (1), pp. 95-109.

Horsthemke, B (2018). A critical view on transgenerational epigenetic inheritance in humans. Nature Communications (9).

Irwin, R.E., Pentieva, K., Cassidy, T., Lees-Murdock, D.J., McLaughlin, M., Prasad, G., McNulty, H. and Walsh, C.P., 2016. The interplay between DNA methylation, folate and neurocognitive development. Epigenomics, 8(6), pp.863-879.

Kaput, J., 2004. Diet-disease gene interactions. Nutrition, 20(1), p.26. 

Koletzko, B., Brands, B., Poston, L., Godfrey, K. and Demmelmair, H., 2012. Early nutrition programming of long-term health. Proceedings of the nutrition Society, 71(3), pp.371-378.

Ilango, S., Paital, B., Jayachandran, P., Padma, P.R. and Nirmaladevi, R., 2020. Epigenetic alterations in cancer. Frontiers in Bioscience-Landmark, 25(6), pp.1058-1109.

Le Doare, K., Holder, B., Bassett, A. and Pannaraj, P.S., 2018. Mother’s milk: a purposeful contribution to the development of the infant microbiota and immunity. Frontiers in immunology, 9, p.361.

Ling, C., 2017. Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomised controlled trial. The American journal of clinical nutrition, 105(4), pp.991-1000.

Littlejohn, P.T., Bar-Yoseph, H., Edwards, K., Li, H., Ramirez-Contreras, C.Y., Holani, R., Metcalfe-Roach, A., Fan, Y.M., Yang, T.M.S., Radisavljevic, N. and Hu, X., 2023. Multiple micronutrient deficiencies alter energy metabolism in host and gut microbiome in an early-life murine model. Frontiers in Nutrition, 10.

Lumey, L.H., Stein, A.D., Kahn, H.S. and Romijn, J.A., 2009. Lipid profiles in middle-aged men and women after famine exposure during gestation: the Dutch Hunger Winter Families Study. The American journal of clinical nutrition, 89(6), pp.1737-1743.

Lustig, R.H. ed., 2010. Obesity before birth: maternal and prenatal influences on the offspring (Vol. 30). Springer Science & Business Media.

Matz, L.M., Shah, N.S., Urban, R.J., Kayed, R. and Buffington, S.A., 2023. Microbiome‐associated metabolic determinants of neurodegeneration and cognitive resilience. Alzheimer’s & Dementia, 19, p.e065786.

Milagro, F.I., Mansego, M.L., De Miguel, C. and Martínez, J.A., 2013. Dietary factors, epigenetic modifications and obesity outcomes: progresses and perspectives. Molecular aspects of medicine, 34(4), pp.782-812.

MM Billah – 2022 – unsworks.unsw.edu.au. Effects of paternal high-fat-diet and micronutrient supplementation on the health outcomes of offspring and grand-offspring. unsw.edu.au

Pannaraj, P.S., Li, F., Cerini, C., Bender, J.M., Yang, S., Rollie, A., Adisetiyo, H., Zabih, S., Lincez, P.J., Bittinger, K. and Bailey, A., 2017. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA pediatrics, 171(7), pp.647-654.

Perfilyev, A., Dahlman, I., Gillberg, L., Rosqvist, F., Iggman, D., Volkov, P., Nilsson, E., Risérus, U. and Ling, C., 2017. Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial. The American journal of clinical nutrition, 105(4), pp.991-1000.

Portincasa, P., Bonfrate, L., Vacca, M., De Angelis, M., Farella, I., Lanza, E., Khalil, M., Wang, D.Q.H., Sperandio, M. and Di Ciaula, A., 2022. Gut microbiota and short chain fatty acids: implications in glucose homeostasis. International journal of molecular sciences, 23(3), p.1105.

Q Shi, K Qi – Pediatric Investigation, 2023 – Wiley Online Library. Developmental origins of health and disease: Impact of paternal nutrition and lifestyle. wiley.com

Ramirez, D. and Haas, S.A., 2022. Windows of vulnerability: consequences of exposure timing during the Dutch Hunger Winter. Population and Development Review, 48(4), pp.959-989.

Romano-Keeler, J. and Weitkamp, J.H., 2015. Maternal influences on fetal microbial colonization and immune development. Pediatric research, 77(1), pp.189-195.

Rosenberg, E. and Zilber-Rosenberg, I., 2021. Reconstitution and transmission of gut microbiomes and their genes between generations. Microorganisms, 10(1), p.70.

Sashital, D.G., Jinek, M. and Doudna, J.A., 2011. An RNA-induced conformational change required for CRISPR RNA cleavage by the endoribonuclease Cse3. Nature structural & molecular biology, 18(6), pp.680-687.

Sippy, T., Chaimowitz, C., Crochet, S. and Petersen, C.C., 2021. Cell type-specific membrane potential changes in dorsolateral striatum accompanying reward-based sensorimotor learning. Function, 2(6), p.zqab049.

Wen, X., Hu, X., Miao, L., Ge, X., Deng, Y., Bible, P.W. and Wei, L., 2018. Epigenetics, microbiota, and intraocular inflammation: New paradigms of immune regulation in the eye. Progress in Retinal and Eye Research, 64, pp.84-95.

Zeisel, S.H., 2017. Choline, other methyl-donors and epigenetics. Nutrients, 9(5), p.445.

Zhang, W., Rodziewicz, G., Voss, M. and Lane, S.D., 2021. Historical Trauma and Epigenetics. The SAGE Handbook of Social Studies in Health and Medicine, p.197.

Ziso, D., Chun, O.K. and Puglisi, M.J., 2022. Increasing Access to Healthy Foods through Improving Food Environment: A Review of Mixed Methods Intervention Studies with Residents of Low-Income Communities. Nutrients, 14(11), p.2278.

Zmora, N., Suez, J. and Elinav, E., 2019. You are what you eat: diet, health and the gut microbiota. Nature reviews Gastroenterology & hepatology, 16(1), pp.35-56.