Overview of foodborne hazards associated with inflammation and metabolic health

Abstract

Access to safe and nutritious food is key to ensuring health and well-being and is critical to meeting the United Nations’ Sustainable Development Goals. However, a synthesis of the associations between foodborne illness and malnutrition, such as metabolic health, remains a gap in the literature base. In this review, we summarized existing evidence on the impacts of biological and chemical hazards on nutrition-related health outcomes, specifically overweight and obesity, inflammation, metabolic disease, thyroid function, cancer development, and adverse birth outcomes, examining physiological mechanisms, epidemiological associations, and animal studies. Mechanisms between some foodborne hazards, such as H. pylori, and adverse pregnancy outcomes, e.g., gestational diabetes mellitus, or between nitrates and impaired thyroid function, are relatively well-studied. However, evidence on the effects of many other chemical hazards on metabolic and human health remains limited: for example, while arsenic exposure is associated with adverse birth outcomes, the limited availability of dose-response studies and other challenges limit ascertaining its causal role. Untangling these associations and physiological mechanisms is of high relevance for both high- as well as low- and middle-income countries. Emerging technologies and novel assessment techniques are needed to improve the detection and understanding of understudied and complex foodborne diseases, particularly those arising from chemical hazards. These evidence gaps are highlighted in this review, as well as the need for establishing surveillance systems for monitoring foodborne diseases and metabolic health outcomes across populations.

Background

The availability of healthy foods that are safe to consume is paramount to achieving global food and nutrition security [1]. Adequate nutrition is crucial to health and well-being; poor-quality (e.g., high-energy with low nutrient density) diets have consistently ranked among the top risk factors for morbidity and mortality worldwide [2, 3] and are often the focus of dietary recommendations, guidelines, and programming. However, improving diets, and subsequently health, requires food to be safe. Food safety, defined as “the absence—or safe, acceptable levels—of hazards in food that may harm the health of consumers” [4] is also critical to achieving the United Nations’ Sustainable Development Goal 2 to “end hunger, achieve food security and improved nutrition and promote sustainable agriculture” [5]. The bidirectional relationship between exposure and impacts of foodborne diseases (FBDs) and health outcomes related to nutrient intake and absorption, inflammation, and metabolic health leading to metabolism-related disorders, and chronic disease development such as cancer [6] is critical to understand but remains mostly overlooked.

FBDs refer to a range of acute and chronic adverse health outcomes caused by foodborne hazards such as pathogenic microbes and helminths, chemical compounds, and biogenic toxins ingested with food [7]. In the longer term, exposure to foodborne hazards exacerbates socioeconomic and health disparities, particularly in low- and middle-income countries (LMICs). While economic consequences can include increased healthcare costs, lost productivity, and declining local and global trade [1], the health impacts of unsafe food are striking. Together, 31 foodborne hazards—including 11 diarrheal disease agents, 10 helminths, seven invasive infectious disease agents, and three chemicals/toxins—were responsible for 600 million episodes of FBD, 420,000 deaths, and 33 million disability-adjusted life years (DALYs) in 2010 [7]. In the most recent 2021 update, the global age-standardized DALYs of enteric infections was 1020.15 per 100,000 population [8].

Many of the major health impacts of compromised food safety are known, as are the major impacts of malnutrition [9]; however, the effects of exposure to foodborne hazards—such as pathogens and chemical agents—on nutrition-relevant outcomes remain poorly understood, in both direction of causality and in their joint contribution to health outcomes [6]. While increasing evidence exists on the association between diarrheal disease and stunting, an endpoint relevant to nutrition, evidence is still scattered on other health endpoints relevant to both foodborne exposure and nutrition, such as inflammation and metabolic health like glucose or lipid metabolism and chronic disease condition like cancer. Chronic low-grade inflammation could disrupt metabolic homeostasis and favor the development of a wide range of noncommunicable diseases (NCDs) such as diabetes, cardiovascular diseases, and cancer [10]. With the rising prevalence of NCDs, it is essential to tackle the related factors across various domains including exposure to foodborne hazards such as cyanogenic glycosides, mycotoxins, or heavy metals.

In this review, we illustrate current evidence examples of physiological or epidemiological associations between acute or chronic FBDs and nutrition-relevant outcomes [6, 11]. We focus on foodborne hazards associated with inflammation and metabolic health endpoints while mentioning that the foodborne hazards associated with gastrointestinal health, nutrient absorption, and growth and development have been extensively reviewed elsewhere [12,13,14].

Type of hazards related to foodborne diseases and their health implications

Biological hazards

Biological hazards include certain bacteria, viruses, protozoa, fungi, and helminths that can result in disease. Among these, bacteria are one of the most prevalent biological foodborne hazards [15]. Acute gastrointestinal illness (AGI) is among the most common manifestations of FBD and presents with a variety of symptoms such as diarrhea with or without hemorrhage, constipation, nausea, vomiting, and abdominal pain, as well as immediate consequences of diarrhea such as dehydration and blood loss. This has been studied in human populations as well as experimental studies and extensively reviewed [12,13,14] and is discussed briefly here. Food- and waterborne AGI are most commonly caused by microbial hazards and often present with diarrheal symptoms. Inflammatory diarrhea—an AGI—can be caused by non-invasive organisms (e.g., non-invasive pathogenic Escherichia coli (E. coli) strains such as enterohemorrhagic E. coli (EHEC)) that stimulate the release of inflammatory mediators in the intestinal mucosa or by invasive organisms (e.g., enteroinvasive E. coli (EIEC), Shigella spp., and Salmonella spp.), via activation of cytokines and inflammatory mediators [16]. Research has suggested that elevated exposure to some enteropathogens, in the absence of diarrheal illness, may adversely impact nutrition outcomes such as growth. It is hypothesized that cryptic enteric pathogen exposure contributes to impairing gut function and altering nutrient absorption and immunity [17]. The evidence of chronic inflammation and reduced intestinal nutrient absorption due to infections and its lasting negative effects on linear growth has been extensively covered by other reviews [18]. The World Health Organization (WHO) identified norovirus, Campylobacter, and non-typhoidal Salmonella as major causes of foodborne diarrhea, with a significant burden in sub-Saharan Africa, where rotavirus, pathogenic E. coli, adenovirus, and Giardia lamblia are common pathogens in children under five [7, 14].

Foodborne pathogens are not only responsible for enteric or diarrheal symptoms but also manifestations including among others fever, pain, kidney failure, hemolytic uremic syndrome, jaundice, meningitis, ulcers, paralysis, miscarriage, and septicemia [19]. Furthermore, acute FBD can lead to severe long-term sequelae including irritable bowel syndrome, inflammatory bowel disease, reactive arthritis, Guillain-Barré Syndrome, neurological and cognitive impairment, and kidney disease, among those currently most supported by evidence as described in a 2019 scoping review [20].

Chemical hazards

Foodborne disease caused by ingested chemicals can result from naturally occurring chemicals (e.g., cyanogenic glycosides in cassava or solanine in potatoes and other Solanaceae plants) or end-products from microbial metabolism, i.e., biogenic chemicals (e.g., mycotoxins such as fumonisins and aflatoxins, or bacterial toxins from spores formed by Bacillus cereus) [21,22,23,24]. There is evidence that mycotoxins, which contaminate a wide range of staple foods across LMICs, potentially contribute to childhood stunting by mediating intestinal damage, inflammation, and the development of environmental enteric dysfunction (EED) [21, 22]. Exposure to foodborne mycotoxins such as aflatoxin, fumosin, and deoxynivalenol is suspected to impair child growth by mediating EED and intestinal damage [21]. Nitrites used in food processing have been associated with higher risks of breast, prostate, thyroid, and colorectal cancers via inhibiting iodide update and the formation of carcinogenic compounds [25, 26].

Exposure to agricultural pesticides, fertilizers, and industrial byproducts through ingested food (e.g., heavy metals like cadmium and arsenic, and polychlorinated biphenyls (PCBs)) have been associated with higher risks of colorectal, liver, and kidney cancers and cardiovascular diseases [23, 27,28,29]. Heavy metals can accumulate in the skeleton and adipose tissues, depleting specific nutrients in the body and resulting in deficits of the central nervous system, as well as cardiac, gastric, hematological, and cognitive function, and intrauterine growth [23, 30]. One example is cadmium, a heavy metal that is toxic to humans [31,32,33]. Dietary cadmium has been shown to promote colorectal cancer metastasis, liver, kidney, and cardiovascular disease [27,28,29]. In terms of arsenic, some evidence suggests that malnourished individuals, regardless of age, are more susceptible to the detrimental health effects—skin lesions, neuropathy, gastrointestinal symptoms, diabetes, cardiovascular disease, and cancer—of dietary arsenic exposure, and these effects can take years of chronic exposure to develop [34]. In addition, PCBs have been known to adversely affect children’s neurological development and increase the risk of attention deficit disorders, autism, cerebral palsy, and mental retardation [23, 35]. Food contaminated by chemicals from PCBs and crop pesticides causes neural and kidney damage, reproductive problems, and cancer [36, 37].

There is evidence from in vitro, animal models, as well as epidemiological studies that endocrine-disrupting compounds (EDCs, also known as endocrine disruptors or hormonally active agents) can leach from everyday products such as plastic beverage bottles and food containers into food and are highly correlated with male and female infertility, obesity, diabetes, and fetal development [38]. EDCs interfere with hormone production, metabolism, and/or transport throughout the body [39]. The common EDCs are PCBs, dichlorodiphenyltrichloroethane (DDT), bisphenol A (BPA), phthalates, and dichlorodiphenyldichloroethylene (DDE).

Chemical hazards can also enter the food system via wastewater. While there are numerous processes in place, e.g., microbial digestion, to remove contaminants from wastewater [40, 41], many chemicals are unaffected by such mitigation leading to their direct consumption through drinking water or food preparation [42, 43]. The potential risk to human health increases when these chemical hazards accumulate in the food chain [42]. Agricultural use of contaminated wastewater on crops can lead to the bioaccumulation of certain contaminants, including heavy metals. If these crops are also used to feed livestock, further bioaccumulation can occur rendering the effective dose of a particular contaminant higher than it would have been at its source (the original wastewater) [42, 44].

Association between food hazards, inflammation, and metabolic health

Table 1 illustrates examples of the impacts of foodborne hazards, both biological and chemical, on inflammation and metabolic health —endpoints that are also relevant to nutrition. Below, we describe these in more detail.

Table 1 Impact of key FBD biological and chemical hazards on inflammation and metabolic health

Overweight and obesity

Foodborne hazards have been associated with weight gain or loss through various pathways. Strong short-term associations exist between AGI and weight loss, while long-term associations are less well defined [59]. Pathogens like Cyclospora cayetanensis, Taenia saginata, Taenia solium, and Cryptosporidium, to name a few, cause loss of appetite, nausea, diarrhea, and vomiting, which eventually leads to weight loss [60]. Helicobacter pylori (H. pylori) infection was also found to be associated with an increased likelihood of hyperemesis gravidarum during pregnancy, which is a severe manifestation of nausea and vomiting, weight loss, dehydration, electrolyte imbalances, and ketonuria in nearly 40 cross-sectional and case–control studies [45]. EDCs have also been hypothesized to induce weight gain, acting as “obesogens,” by interfering with the endocrine system [61], via pathways such as increased oxidative stress and lowered thyroid hormone levels, due to organochlorine pesticides and PCBs, and slower metabolic rates [62]. Other hormones that are also affected by chemical toxins are estrogen, testosterone, corticosteroids, insulin, growth hormone, leptin, and catecholamines [63]. Agents with obesogenic potential (e.g., persistent organic pollutants (POPs), BPA, PCB) can act through impairing thermogenesis, increasing adipocyte cell differentiation, or interaction with steroid hormone receptors [54, 55]. Mechanisms for POP-related obesity in humans are incompletely understood; however, evidence from in vivo and in vitro studies suggests thermogenesis impairment through a decrease in brown adipose ribonucleic acid [52]. In contrast, BPA has been suggested to cause an increased adipocyte cell differentiation leading to excess fat accumulation [55], while PCBs have been suggested to antagonize steroid hormone receptors or induce specific metabolic pathways that can either increase or decrease body weight [52, 54, 55]. The evidence on the effects of chemical hazards and body weight is variable, highlighting a need for further research.

Metabolic disease

Metabolic disease can impair physiological processing and use of nutrients, hence affecting nutrition processes and outcomes. Several foodborne hazards have been associated with metabolic disease. Chemical hazards that can affect glucose metabolism include phthalates, which can alter receptors that contribute to adipogenesis, lipid metabolism, and metabolic homeostasis, or act via induction of oxidative damage [51]. H. pylori is a pathogen highly prevalent in LMICs which can be spread through feces as well as contaminated water and food [64, 65]. H. pylori infection contributes to metabolic disease via different pathways—for example, one review found H. pylori-induced inflammation caused insulin resistance and the development of diabetes mellitus [66]. H. pylori has also been shown to cause changes in perinatal glucose metabolism and subsequently inhibit insulin-receptor interactions, leading to strong associations with gestational diabetes mellitus [46]. It can also affect the production of the hunger hormones ghrelin and leptin subsequently modulating the secretion of the growth hormone [65], which may lead to growth retardation among malnourished children or children exposed to H. pylori in early childhood [65, 67, 68]. In addition, epidemiological evidence suggests that H. pylori infection affects micronutrient status through various mechanisms, including inhibiting iron absorption by inducing the conversion of ascorbic acid (vitamin C) to dehydroascorbic acid; changing gastric pH which in turn causes malabsorption of dietary cobalamin and inactivation of ingested vitamin C, inhibiting vitamin B₁₂ absorption, and lowering the mucosal concentration of α-tocopherol (vitamin E) in the colon [65].

An additional foodborne pathogen, Toxoplasma gondii (T. gondii), is a protozoan parasite for which one-third of the world population is seropositive. The prevalence between communities can range between 10 and 90% [69], with contaminated meat and dairy representing the main source of infection [70, 71]. The prevalence of latent toxoplasmosis in pregnant women is estimated to be the highest in South America [72] with prevalence on the decline in certain developed countries, possibly due to changes in food habits and improved hygiene [73]. Infection with the parasite is difficult to detect as most healthy people with toxoplasmosis are asymptomatic; acute flu-like symptoms occur in only 20% of infected individuals. T. gondii may contribute to type 2 diabetes mellitus (T2DM) development via different pathways: it can trigger an autoimmune response eventually causing inflammation of the Langerhans islets, a pancreatic tissue, or directly invade and destroy pancreatic β cells [50, 74]. While the association between T. gondii and T2DM is supported by epidemiological research [75], its exact mechanisms in T2DM pathogenesis remain understudied, though recent work points toward T. gondii’s manipulation of the host cell metabolic environment [69].

There is mounting in vitro, in vivo, and epidemiological evidence that EDCs, particularly phthalates, BPA, and acrylamides have also been identified as playing roles in diabetes development and progression [76] as well as obesity [77]. These chemicals can interfere with glucose and lipid homeostasis, including affecting the function of beta-cells in the pancreas [77]. A report from the European Union found that EDC exposures contribute substantially (20–69% depending on the EDC) to both diabetes as well as obesity in children, adults, and older women, with a probability of > €18 billion in costs per year [78]. Heavy metals like arsenic and cadmium can cause insulin resistance leading to T2DM. Arsenic and cadmium inhibit proliferator-activated receptor γ, which plays a crucial role in glucose metabolism. Cadmium also induces pro-inflammatory lipids and cytokines which are associated with chronic inflammatory diseases like obesity and T2DM. This has been extensively covered in a recent review [79].

Food additives like nitrates and nitrites, e.g., food dyes, titanium dioxide, phosphate-containing additives, artificial sweeteners, and emulsifiers, are often used to enhance the taste, texture, and shelf life of food, may also pose chemical hazards. While food additives are subjected to rigorous toxicity assessments, some studies raise concerns about their safety. For example, there are mixed associations between metabolic syndrome and non-caloric artificial sweeteners (NAS), such as sucralose, saccharine, and aspartame. As their name indicates, they are low in calories while still providing sweetness to foods. In contrast to energy-containing sugars such as sucrose, NAS passes through the digestive system without being digested and absorbed by the host, instead directly encountering the colonic microbiota [80]. Some studies have found that NAS improved glycemic response, while other studies have found NAS caused weight gain and a higher risk of T2DM in humans [80]. In animals, NAS consumption has been associated with more adverse outcomes. For example, aspartame at doses 7–15% of the maximum recommended daily intake caused learning and memory deficits in mice, which were passed down to offspring [81]. In another study, saccharin, sucralose, and aspartame consumption by mice, dose exceeding 5 mg/kg of body weight (the acceptable daily intake limit set by the US Food and Drug Administration) caused impaired glucose tolerance, which was mediated by changes in the gut microbiome, including increases in the abundances of taxa associated with T2DM in humans [80]. This topic has been reviewed extensively elsewhere [82, 83]. A thorough review of other food additives and human health remains less explored in the literature but is beyond the scope of the current manuscript.

Thyroid function

Thyroid hormone and its optimal functioning are essential for regulating metabolism in humans. The association between thyroid hormone, body weight, and energy expenditure is well established. Excess production of thyroid hormone could induce weight loss, increased energy expenditure, reduced cholesterol levels, and increased lipolysis and gluconeogenesis. Low hormone levels could increase weight gain, reduce energy expenditure, and increase cholesterol levels [84]. A systematic review and meta-analysis found that exposure to nitrites and nitrates has been associated with inhibition of iodine uptake and resulting impaired thyroid function, which can cause hypertrophy and goiter development, in humans part of experimental and clinical studies [53]. Environmental toxins can affect women’s reproductive health by increasing the risk of cancer and ovulatory dysfunction. EDCs have been shown to cause reproductive development disorders, subfertility, and polycystic ovarian syndrome in women [85]. Higher serum BPA concentrations also contribute to these factors in addition to increasing insulin resistance and hyperandrogenism.

Cancer development

The carcinogenic potential has been attributed to various foodborne hazards, mostly chemical but also biological. For example, epidemiological evidence has shown H. pylori infection or aflatoxicosis is associated with an increased risk of stomach cancer across several systematic reviews and meta-analyses [47,48,49], cadmium ingestion was shown to play a role in colorectal cancer metastasis via cell culture in vitro and in mice [29], and dietary nitrites and nitrates from processed meats have been associated with greater risks of breast, prostate, thyroid, and colorectal cancers among adults in large cohort studies [25, 26] (Table 1). The colonization of H. pylori in the stomach may lead to stomach cancer from chronic gastric inflammation, hypochlorhydria (decreased gastric acid secretion), and immunomodulation [47,48,49]. Cadmium may increase metastasis through epidermal growth factor receptor signaling [29]. Nitrites, commonly used as a food additive in processed and cured meats, combine in the human body to form carcinogenic N-nitroso compounds (NOCs). Circulating vitamins C and E have been shown to inhibit the metabolism of NOCs in the gut [86].

Birth outcomes

Foodborne hazards can jeopardize the health and nutritional status of pregnant women and newborns, affecting a range of development endpoints for the fetus and infant, as well as the health of the pregnant woman. Several systematic reviews have found H. pylori infection was associated with an increased risk of gestational diabetes [46], and mycotoxin and arsenic exposure impaired fetal growth and neurologic function [57, 87]. Arsenic can cross the placenta and accumulate in developing fetal organs, as well as in the placenta leading to disruption or alteration of cord blood methylation [56, 57]. Arsenic has also been identified as a potential risk factor for adverse birth outcomes such as neural tube defects as described in a systematic review and meta-analysis [88], which could be a result of increased fetal folate requirements due to arsenic exposure [89, 90]. However, more research is needed to ascertain the causal association between arsenic due to limited studies on dose response and methodological challenges [88]. Mercury and lead toxicity have been associated with poor fetal development and are known causes of neurodevelopment disorders in offspring. These heavy metals also lower maternal manganese and zinc levels during the prenatal period and 5 months postnatally [63].

Population considerations

High-risk populations

Foodborne pathogens are more likely to cause severe disease in individuals with weakened or immature immune systems. Immunologically vulnerable groups including infants and young children, pregnant women, the elderly, and immuno-compromised individuals may be at increased risk of contracting food-related diseases [7]. The extent to which vulnerable populations are more susceptible to short- and long-term adverse FBD-related nutritional outcomes as compared to non-vulnerable groups has not been established. Children under 5 years of age carry a large proportion (40%) of the disease burden attributable to FBD, despite representing only 9% of the global population [7]. Given their developing immune system and small body size, malnourished infants and children are at higher risk of developing serious forms of foodborne diarrheal diseases—exacerbating malnutrition and further increasing the morbidity and mortality risk [7, 91]. Children can also exhibit behaviors that can lead to FBD, for example, by eating food contaminated with soil or animal feces [92].

Gender and occupational factors

Gender and occupation are important determinants of FBD exposure and potential drivers of adverse health outcomes. A recent assessment of traditional livestock and fish value chains in 20 LMICs identified socially constructed gender differences in exposures and occupations as major drivers of FBD in 19 of 20 reviewed studies [93]. While men are more likely to sustain injuries associated with livestock production, fishing, hunting, and slaughterhouse work, women are more exposed to foodborne pathogens during food processing, selling, and preparation [93]. These risks are particularly relevant in the context of traditional markets where vendors and food handlers are in close and frequent contact with food and food-contact surfaces that can be highly exposed to foodborne or zoonotic pathogens [94]. Differences in FBD outcomes attributable to sex or biology have been identified for several FBD-related pathogens. For example, susceptibility to Listeria monocytogenes infection is elevated during pregnancy [93], whereas invasive amebiasis is more common in adult males than females, though no gender differences have been reported in children [95]. A possible sex-dependent association between arsenic exposure and child growth in girls has also been identified [56]. Likewise, PCB exposure was associated with obesity in girls, whereas prenatal PCB exposure was associated with reduced birth weight among male infants [55].

Research gaps and future directions

In this review, we have examined the epidemiological, animal, and in vitro evidence on the associations between foodborne biological or chemical hazards, and nutrition-related outcomes including overweight and obesity, metabolic health, thyroid function, cancer development, and adverse birth outcomes. We have also considered gender differences in exposure to these hazards, noting the particular risks for women. Findings demonstrate that integration of food safety and nutrition programs is critical to improving population health (Fig. 1). Risks associated with unsafe foodborne hazards are substantial, and there are ongoing efforts to systematically quantify them at the global level [7]. The lack of certainty of evidence, as well as limited data attributing disease burden to specific foodborne hazards or food categories, limits the ability for an adequate response [96]. Evidence points toward a negative impact of certain hazards on nutrient absorption (e.g., helminths, H. pylori) and metabolic functions such as glucose and thyroid metabolism (e.g., persistent organic pollutants and other chemicals), as well as gastrointestinal ulcers (H. pylori). For some hazards (e.g., H. pylori), mechanisms are better understood, at least partially, because they have been investigated for decades, while there is limited evidence on the effects of other biological and chemical hazards on metabolic and human health due to a small number of studies and methodological differences, such as T. gondii and T2DM pathogenesis. For most associations between foodborne hazards and health outcomes, cytokine-induced inflammation serves as an intermediary pathway. EDCs cause mitochondrial dysfunction with an increase in reactive oxygen species, causing inflammation-induced obesity. Biological hazards such as H. pylori and T. gondii can produce inflammatory cytokines leading to insulin resistance and T2DM. Heavy metals like lead and cadmium can also produce oxidative stress and inflammation causing insulin resistance. Emerging technologies may allow for more accessible (i.e., cheaper and faster) detection and mechanistic assessment of currently understudied hazards. There is also a need to identify novel metrics or techniques for assessing more complex foodborne diseases.

Fig. 1

Comprehensive overview of health outcomes of foodborne diseases and future directions. As, arsenic; BPA, bisphenol A; Cd, cadmium; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; PCBs, polychlorinated biphenyls; PFASs, perfluoroalkyl and polyfluoroalkyl substances. Created in BioRender

Given the high complexity of foodborne hazards and metabolic health outcomes combined with a lack of consistent data, this review contextualized the available evidence on how FBD impacts physio-pathological processes. Other relevant health implications, such as the impacts of FBD on cognitive development or impaired work productivity are beyond the scope of this article. Mortality resulting from FBD was not extensively reviewed but should be acknowledged as the extreme boundary of FBD-related detrimental health impacts. This review highlights the physiological impacts of FBD; however, non-physiological effects, such as modified consumption behavior in response to FBD scares or outbreaks as well as other socioeconomic aspects were not considered. These behavior changes could have important nutrition impacts. With the growing consumer interest in organic foods, it is important to compare the foodborne hazards associated with organic produce to those of conventionally grown crops. While organic foods may contain lower levels of pesticide residues, studies have found no significant differences in contamination levels of heavy metals, mycotoxins, or bacteria [97]. We refer the reader to a recent systematic review on the impact of organic foods on chronic diseases [98]. Further, the effects of per- and polyfluoroalkyl substances (PFASs), which have pleiotropic effects on human health through endocrine functions were not covered here but can be found in the review by Gaillard et al. [99]. PFASs are found to disrupt thyroid function and hormone synthesis and are associated with metabolic syndrome [100].

Programs and research efforts examining the impact of FBDs on health and nutrition status, possibly including causal and enabling factors, health outcomes, or potential mitigating actions are rare but exist. For example, research efforts such as the MAL-ED study investigated the interaction between enteric disease and malnutrition in birth cohorts across eight countries [101]. Other projects have jointly measured enteric illness and nutrition endpoints to evaluate the impact of food safety, water, sanitation, and/or nutrition interventions [102]. In the USA, federal nutrition programs could be leveraged to address food safety. The special supplemental nutrition program for Women, Infants and Children (WIC) protects beneficiaries from lead exposure by providing food packages that are rich in vitamin C, calcium, and iron—these nutrients help to limit lead absorption in the body [103]. Food safety regulations in the US are designed by the Food and Drug Administration (FDA) known as the Integrated Food Safety System (IFSS). The IFSS provides vision, guiding principles, and key components of a coordinated approach to food safety. This involves continuous improvements and collaboration through multiple initiatives, programs, and projects [104]. Further, the Food and Nutrition Service (FNS) under the U.S. Department of Agriculture develops food safety education, training, and technical assistance resources to support FNS program operators [105].

Further, there are regulations and standards for the use of PCBs under the Toxic Substances Control Act which addresses the production, importation, use, and disposal [106]. However, these programs and regulations focus on public health generally. The regulation to address the nutritional impact of foodborne hazards is often overlooked. Globally, the Codex Alimentarius—a joint Food and Agriculture Organization (FAO) and WHO Food Standards Program—formulates a voluntary international standard, codes of practice, and guidelines to promote the health of the consumers and ensure fair practice in food trade [107]. This also overlooks the direct impact on the nutritional status of the population. In contrast, the U.S. Agency for International Development (USAID) Feed the Future: EatSafe program worked with traditional markets in Nigeria and Ethiopia to improve food safety by engaging and empowering consumers and vendors to demand safe, nutritious food through food safety interventions [108]. The EatSafe program is also facilitating the development and adoption of international standards for food safety in traditional markets [109, 110]. This type of program ensures appropriate implementation of regulations and ensures safe and nutritious food for population health.

Methodological differences across disciplines arise when examining the effect of agriculture interventions on nutrition status [111], and similar challenges are evident when connecting food safety, nutrition, and public health, emphasizing the need to harmonize the interpretability and actionability of current research. Longitudinal studies are required to better assess the temporal relationships and long-term impacts of FBDs on nutritional outcomes. To assess the impact at the population level, there is a need for consistent surveillance of FBDs and metabolic health outcomes. Of note, the FDA recently launched a new unified Human Foods Program. This initiative aims to enhance public health through science-based strategies to prevent foodborne illnesses, reduce diet-related chronic diseases, and ensure the safety of chemicals in food. The program focuses on three key areas: microbial food safety, chemical food safety, and nutrition, through the Nutrition Center for Excellence. While each area will operate independently with its own priorities, they share a common vision of making food a source of wellness for everyone [112]. More such transdisciplinary and intersectoral efforts are needed across the globe to fully understand the burden of FBDs, and the role of other associated risk factors including available treatments, sex, gender, and environmental stressors to inform the design of effective programs and interrupt the cycle of poor food safety, malnutrition, and health.