Project Newsletter | Winter 2023/24

Recapping our research focus

Our first paper described the overall design of the HEDIMED project. It was published as a review article together with other European Human Exposome Projects in the Journal of Environmental Epidemiology. The main goal summarizes well the key determinants:

“The main goal of HEDIMED is to identify the complex interactions between external and internal exposomes and the key molecules and pathways that are critical for the development of type 1 diabetes, celiac disease, allergy, and asthma. HEDIMED fills critical knowledge gaps that have hindered the identification of exposomic determinants of immune-mediated diseases (IMDs) and thereby facilitate the development of prevention and better treatments and diagnostics for IMDs.” 

Research publications

This is an overview of the published original articles categorised by exposomic factors. Also look at our website for background information on the immune-mediated diseases studied in HEDIMED.

Viral infections

Viral infections are possibly associated with the development of different autoimmune diseases, and in HEDIMED they are also one of the key exposomic factors studied. The first published virus-related HEDIMED paper was by Tapia et al., where the authors wanted to study whether early-life parechovirus and anellovirus infections were associated with subsequent development of celiac disease.

Parechoviruses are common enteric viruses, which often infect children without clinical symptoms. Another investigated virus group was anelloviruses, which are persistent human viruses, which have been seen to be related to the human immune system.

Longitudinal early-life samples from children who later developed celiac disease and from their matched controls who didn’t get the disease were included. Transglutaminase 2 antibodies, a marker of celiac disease autoimmunity, were determined from blood samples, whereas viruses were quantified in stool samples. The samples were from Norwegian MIDIA study of children at genetic risk of celiac disease.

The results showed that parechovirus infections were detected in 11% of the samples studied and were more frequent in children who later developed celiac disease-related autoantibodies compared to controls. Anelloviruses were detected in 84% of the samples without any statistical differences between the case and control subjects. In conclusion, it might be beneficial to find ways to prevent parechovirus infections, if the result gets more support in future research.

Read: Parechovirus Infection in Early Childhood and Association With Subsequent Celiac Disease

Probiotic supplementation

Lactiplantibacillus plantarum and Lacticaseibacillus paracasei are commonly included in probiotic supplements. It’s assumed that they have many positive effects on human health. In the following two studies, researchers investigated some specific effects the supplements could have on the human gut.

A randomised, double-blinded placebo-controlled clinical trial was carried out to study the effect of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei supplementation on the stool metabolome in children with celiac disease autoimmunity (screened positivity on Transglutaminase 2 antibodies).

The study by Jeníčková et al., showed that the combination of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 showed marginal, yet significant changes in the levels of numerous stool metabolites after 6 months of intervention. Changes consisted mainly differences in amino acid profiles, indicating a shift towards known healthier metabolic patterns.

Read: Effects of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei supplementation on the faecal metabolome in children with coeliac disease autoimmunity: a randomised, double-blinded placebo-controlled clinical trial

The second paper by Hurych et al. is based on the same trial and focused on the single-cell faecal parasitome. The researchers studied how a probiotic intervention affects beneficial intestinal protists in children with celiac disease autoimmunity. It was found that there isn’t any significant effect. The level of protist colonisation stayed low and stable regardless of the probiotics. The researchers were surprised, that the presence of the beneficial protists was inversely associated with gut-health-promoting bacteria. 

Read: Effects of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei supplementation on the single-cell fecal parasitome in children with celiac disease autoimmunity: a randomized, double-blind placebo-controlled clinical trial

Food microbiome

It’s known that microbes and their diversity in the human gut have an effect in many ways on human health, even though many mechanisms remain unclear. But which factors are affecting the gut microbiome? One of those is quite evidently the food we eat. Therefore, it’s important to investigate, what affects the food microbiome and how it can modulate our gut’s microbiome.

To investigate the impact of cultivation methods, researchers / Wicaksono et al. collected samples from both, naturally grown (wild or home gardens) and horticultural, apples and blueberries, and compared the microbiome compositions of each sample.  They discovered that the cultivation methods highly affect the microbial species and diversity of the berries and fruits. Horticultural products have a more homogenous microbiome in comparison to naturally grown ones.

Read: Impact of Cultivation and Origin on the Fruit Microbiome of Apples and Blueberries and Implications for the Exposome

In another study Wicaksono et al. characterized the structure and function of the apple microbiota. the study group found that some of the bacteria may have beneficial health effects. To find out how processing affects bacterial abundance and diversity, the researchers analyzed unprocessed apples and apples processed in several ways, which have been commonly used in manufacturing food products for infants.

The group found that the processing of apple fruits decreased the level of bacterial load and diversity. Additionally, it shifted the bacterial community structure. This might reduce the potential health effects of apple consumption.

Read: Modulation of the food microbiome by apple fruit processing

You can also read the HEDIMED blog post on this topic!

The latest research on the food microbiome was carried out by profiling the microbial communities of the human gut and fruits and vegetables. Wicaksono et al. reconstructed representative genomes of fruit- and vegetable-related bacteria from 156 fruit and vegetable metagenomes (which means the recovery and complete sequencing of genetic material extracted from the samples). The genomes were used as a basis to investigate the prevalence of fruit- and vegetable-associated bacteria in selected 2,426 publicly available gut metagenomes.

The results from DAIBIMMUNE cohort data (1,154 stool metagenomes from 269 individuals), showed that the fruit and vegetable -related bacteria composed an average of 2,2% of the overall gut bacterial diversity, ranging from 0.8% to 13.6%.) Additionally, the analysis of the American Gut Project data (964 metagenome) showed that the frequency and the diversity of consumed fruits and vegetables were associated with the richness of fruit and vegetable-related bacteria in the human gut.

Read: The edible plant microbiome: evidence for the occurrence of fruit and vegetable bacteria in the human gut

Also take a look at the press release of the study by Graz University of Technology and the EU cordis news about the results.

It was the first time, that the fruit and vegetable-associated bacteria were discovered in the human gut. The researchers concluded that as the fruit and vegetable microbiome can colonize the human gut, it’s important to pay attention to the fruit and vegetable microbiome that we consume, and thus further the cultivation and processing methods affecting the microbiome.

Microbiome of the living environment

It has been suggested that environmental microbes are possibly affecting the human immune system and that nature-based diverse environmental microbiome would be more beneficial than urban.

To find proof for the hypothesis, it’s vital to control other factors which could affect the relationship between environment and immune regulation. In one placebo-controlled, double-blinded trial Roslund et al. investigated the effects of microbially enriched sand on playschool children’s microbiome and immune regulatory system.

The children played with sandbox sand which was enriched with nature-based microbes. In the control group, children were playing with normal, similar-looking, sandbox sand. Sand, skin, stool bacterial and blood samples were taken in both groups at the beginning of the study and after 14 days intervention. In the blood samples of the children who played with the modified sand were discovered changes in plasma cytokines and immunoregulatory cells and children’s skin microbiota were more diverse in comparison to the control group. The differences in microbiota between the two groups were not observed anymore two weeks after the intervention period on day 28.

Read: A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children

It has also been studied, how the overall living environment might modulate the autoimmune disease risk.

By using satellite and map-based land cover data, Nurminen et al. compared the first year’s living environment of children who later got type 1 diabetes or the preclinical state of the disease, and the children who did not. Additionally, the study group analyzed the microbial communities of the doormats of 22 study participants.

An agricultural environment was associated with reduced risk of type 1 diabetes. It was also shown that snow cover affects the load of microbes transferred indoors, which possibly explains the difference seen in the strength of the connection between residential areas, as the length of the snowy period differs a lot between south and north. The results demonstrated that land cover of the living environment from birth to 1 year age might influence the risk of type 1 diabetes, and the association may be modulated by the environmental microbial diversity.

Read: Land Cover of Early-Life Environment Modulates the Risk of Type 1 Diabetes

In Voor’s et al study, land cover was associated also with atopic sensitization. The researchers investigated how a combination of various green area types (e.g. forest and grasslands) at radiuses of 1–10 km around homes of infants was related to signs of atopy during the first nine years of life.

The key message of the research is that green environments around infants’ homes are associated with a lower risk of atopic sensitization. Especially, forests, wetlands and grasslands seem to have a protective association.

Read: Atopic sensitization in childhood depends on the type of green area around the home in infancy

All three studies support the biodiversity hypothesis. Among other benefits, contact with natural environments might play a role in modifying immunoregulation. In our project, more studies are ongoing utilizing land cover / satellite data. You can also read more about this topic in our blog post on satellite data studies.


Perfluoroalkyls are a diverse group of synthetic chemicals with multiple sources in modern society, and they have been seen as potentially harmful to human health in several ways.

Sevelsted et al. examined, how exposures during pregnancy and in early life to PFOA and PFOS are associated with several health conditions such as childhood infections, asthma, allergic sensitization, atopic dermatitis, and lung function measures. The study subjects were population-based with 738 pregnant women and their children from the Danish COPSAC2010 cohort. The researchers analyzed their plasma PFOS and PFOA concentrations, from mothers on gestation week 24 and 1 week after delivery and children on the age of 0,5, 1,5 and 6 years.   All the children were closely followed in COPSAC research, so their health data was extensive.

It was found, that prenatal exposure to PFOS and PFOA increased specifically the risk of low prevalent non-atopic asthma, whereas there was no effect on atopic asthma, lung function, or atopic dermatitis. The association wasn’t found regarding childhood exposure.

Read: Exposures to perfluoroalkyl substances and asthma phenotypes in childhood: an investigation of the COPSAC2010 cohort

Omega-3 fatty acid

Intake of Omega-3 fatty acids is included in general dietary recommendations, as it has been shown to have multiple health effects. Regarding type 1 diabetes there is some evidence that higher use of omega-3 fatty acids in the early years of life could reduce the risk of the disease and its’ preclinical state (e.g. take a look at a previous DIPP cohort study on omega-3 acids)

Lund-Blix et al. investigated if long chain omega-3 fatty acid intake during pregnancy is associated with lower type 1 diabetes risk in the offspring. Two large birth cohorts, the Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on long chain omega-3 fatty acids (EPA and DHA) intake during pregnancy using validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries, and the dietary information of the diagnosed children was compared to the information of the children who didn’t get the disease. Contrary to what the hypothesis suggested, there wasn’t found an association between maternal prenatal long chain omega-3 fatty acid intake and the disease risk of the children.

This publication is still a preprint and it was published in medRxiv.

Read: Long chain omega-3 fatty acid intake in pregnancy and risk of type 1 diabetes in the offspring: Two large Scandinavian pregnancy cohorts – MoBa and DNBC

The European Human Exposome Network

The European Human Exposome Network (EHEN) is the world’s largest network of projects studying the impact of environmental exposure on human health. It brings together 9 EU research projetcs that address issues such as exposures to air quality, noise, chemicals, urbanisation etc. and health impacts. 

Read more about EHEN and see their latest news.

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