# Territory Health: A Transdisciplinary Approach of Environmental, Plant, Animal, and Human Health Interdependencies in a Rural Landscape in France

Sabrina Gaba, Sandrine Lefeuvre, Frédéric Ouédraogo, Céline Mougard, Eloïse Brillard, Fleur Delva, Antoine Dupuis, Alain Monnereau, Jérôme Moreau, Karine Monceau, et al.

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Sabrina Gaba, Sandrine Lefeuvre, Frédéric Ouédraogo, Céline Mougard, Eloïse Brillard, et al. Territory Health: A Transdisciplinary Approach of Environmental, Plant, Animal, and Human Health Interdependencies in a Rural Landscape in France. iScience, 2026, pp.114956. 10.1016/j.isci.2026.114956. hal-05516373

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*Territory Health:* A Transdisciplinary Approach of Environmental, Plant, Animal, and Human Health Interdependencies in a Rural Landscape in France

Sabrina Gaba, Sandrine Lefeuvre, Frédéric Ouédraogo, Céline Mougard, Eloïse Brillard, Fleur Delva, Antoine Dupuis, Alain Monnereau, Jérôme Moreau, Karine Monceau, Raphaëlle Teysseire, Nicolas Benvegnu, Vincent Bretagnolle

PII: S2589-0042(26)00331-7

DOI: https://doi.org/10.1016/j.isci.2026.114956

Reference: ISCI 114956

To appear in: *iScience*

Please cite this article as: Gaba, S., Lefeuvre, S., Ouédraogo, F., Mougard, C., Brillard, E., Delva, F., Dupuis, A., Monnereau, A., Moreau, J., Monceau, K., Teysseire, R., Benvegnu, N., Bretagnolle, V., *Territory Health:* A Transdisciplinary Approach of Environmental, Plant, Animal, and Human Health Interdependencies in a Rural Landscape in France, *iScience* (2026), doi: https://doi.org/10.1016/j.isci.2026.114956.

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# Territory Health: A Transdisciplinary Approach of Environmental, Plant, Animal, and Human Health Interdependencies in a Rural Landscape in France

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## Authors

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Sabrina Gaba¹,²,§, Sandrine Lefeuvre³,⁴, Frédéric Ouédraogo⁵,⁶, Céline Mougard⁵, Eloïse Brillard³, Fleur

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Delva⁶,⁷, Antoine Dupuis³,⁴, Alain Monnereau⁶,⁷, Jérôme Moreau²,⁵, Karine Monceau²,⁵, Raphaëlle

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Teysseire⁶, Nicolas Benvegnu⁸ and Vincent Bretagnolle²,⁵

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¹ Centre d'Etudes Biologiques de Chizé, USC1339 CNRS INRAE La Rochelle Université, 79360 Villiers-en-Bois, France

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² LTSER Zone Atelier Plaine & Val de Sèvre, 79360 Villiers-en-Bois, France

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³ Université de Poitiers, CNRS 7267, Laboratoire EBI, Équipe IHES, 86000 Poitiers, France

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⁴ Laboratoire de Pharmacocinétique et Toxicologie, CHU de Poitiers, INSERM CIC 1402, Axe EATHER, 86000

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Poitiers, France

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⁵ Centre d'Etudes Biologiques de Chizé, UMR7372 CNRS La Rochelle Université, 79360 Villiers-en-Bois, France

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⁶ Bordeaux Population Health Research Center, Inserm UMR1219-EPICENE, University of Bordeaux, 33076

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Bordeaux, France

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⁷ Department of Occupational and Environmental Medicine, Bordeaux Hospital, 33000 Bordeaux, France

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⁸ Médialab, Sciences Po, 75007 Paris, France

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§ Corresponding author: Sabrina Gaba, sabrina.gaba@inrae.fr, 405 route de Prissé la Charrière, F79360 Villiers-

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en-Bois, +33549099601
## 22 SUMMARY

Health is increasingly understood as an integrated property of human, animal, plant, and environmental systems, as articulated by the One Health and EcoHealth concepts. The *Territory Health* project applies these perspectives within an agricultural landscape to examine interdependencies between environmental, non-human organisms, and human health. Using in a participatory and experimental approach, the project brings together researchers, local residents, farmers, decision-makers, and NGOs to investigate the relationships between pesticide use, *in situ* exposure to pesticide mixtures, and health effects on non-target organisms. A key objective is to establish a "partner cohort" to examine how changes in food production, dietary practices, and the human-nature relationship shape health of the territory under study. By situating the food-biodiversity-environment-health nexus within a socio-ecosystem perspective, this work supports agrifood system transformations toward long-term territorial health.

## 34 KEYWORDS

Biodiversity, Birds, Cohort, Ecosystem Health, Experiment, Human Health, Knowledge Co-production, Nature-Based Solutions, Organic Farming, Transdisciplinary Research
37 INTRODUCTION

38 There is now little doubt that humans impact and transform their environments¹ and that, in return, those
39 changing environments impact social and economic development or human health to such an extent
40 that they represent an existential risk to societies ². Industry, energy, and transportation have contributed
41 to the crossing of critical planetary boundaries. Among human activities, agriculture is, however, by far
42 the most stressful to the environment ³,⁴, causing the earth system to pass critical boundaries and tipping
43 points ⁵, through climate change, habitat destruction, increasing landscape homogenization, and
44 biodiversity loss ⁶. The latter, i.e. declines in insects, birds, and aquatic organisms, has been associated
45 at least in part to pesticide use ⁷,⁹, which has further negative effects on human health ¹⁰⁻¹², and a
46 decrease in air, water, and land quality¹³. Recently, pesticide use has prompted social concerns¹⁴,
47 resulting in the launch of several political initiatives to, for instance, ban the use of synthetic pesticides
48 (e.g., #StopGlyphosate; https://www.pan-europe.info/stop-glyphosate) or call for bee-friendly agriculture
49 to benefit farmers, health, and the environment (Save Bees and Farmers;
50 https://www.savebeesandfarmers.eu/eng). As a consequence of growing evidence on their detrimental
51 impacts on biodiversity, some pesticides—such as dichlorodiphenyltrichloroethane (DDT) and
52 neonicotinoids—have been withdrawn from the European market ¹⁵. However, banning one chemical
53 can result in the use of others, or in alternative practices that are harmful to biodiversity or associated
54 with increased greenhouse gas emissions¹⁶. A well-documented example is the replacement of
55 glyphosate with mechanical tillage, which often results in increased soil erosion and greenhouse gas
56 emissions ¹⁷. Pesticide use can, therefore, be considered as a wicked problem spanning human, non-
57 human organisms, and environmental health and having multiple interconnected economic, social, and
58 environmental facets¹⁸.

59 Assessing the effects of pesticide use on biodiversity, human health, and the environment, and
60 developing solutions to this wicked problem requires whole-system thinking to adequately grasp the
61 interrelationships between the multiple causal factors. In rural landscapes, the environment, non-human
62 organisms, and humans are typically exposed to various synthetic chemicals at the same time. For
63 instance, over 380 molecules and 309 different compounds are applied, generally in a mixture, to protect
64 cereals in Switzerland (https://www.fedlex.admin.ch) or France (https://ephy.anses.fr/). Yet, risk
65 assessments in Europe and the United States are currently established on standardized trials based on
66 the use of a single pesticide substance or product on a specific crop 6. Moreover, non-target organisms,
67 humans (usually agricultural workers), and the environment are repeatedly, sometimes continuously,
68 exposed to pesticides, resulting in long-term effects occurring after chronic exposure with variable time
69 lag 19-21. Thus, delayed or lagged non-lethal or sublethal effects also need to be evaluated. Since they
70 are seldom quantified in natura, this can lead to the underestimation of pesticide effects on non-target
71 organisms in laboratory assessments, which may account for the repeatedly observed contrasting
72 results when comparing in situ and laboratory assessments (see 22,23 for examples on bees and
73 neonicotinoids). To add to this complexity, such assessments need to consider agricultural landscapes
74 as mosaics of several crops, the composition of which varies greatly across time and space. This
75 heterogeneous composition results in spatio-temporal variation in the type and intensity of pesticide
pressure—i.e., the pesticides and the amount of each being applied to a crop type—and hence also varied exposure. Despite the presence of pesticide residues in air²⁴, soil²⁵, rain²⁴, groundwater and surface water²⁶,²⁷, plants²⁸,²⁹ and animals²⁰, and even humans³⁰ having been confirmed in many studies highlighting the widespread environmental contamination by chemical compounds and their by-products and raising concerns about their long-term ecological and health impacts, only a static picture emerges. Indeed, the important dynamic processes that involve the interaction between these components, the mobility of living organisms, including humans, and the detoxification, persistence, bioaccumulation, and biomagnification processes, are still not captured.

A good example is provided by the most widely used herbicide, glyphosate (commercially known under trade names such as Roundup™). It is far more persistent than initially believed and was detected in 30% of global cropland soils³¹, and in earthworms³², and in rodents³³ in its unaltered form. Recent studies also emphasize that glyphosate residues in soils and biota may disrupt microbial communities³⁴ and affect soil biodiversity, further exacerbating environmental risks³⁵,³⁶. Its primary metabolite, aminomethylphosphonic acid (AMPA), is even more pervasive, being found in over 90% of global cropland soils³¹, as well as in earthworms³² and rodents³³. Finally, assessments of pesticide effects typically have a narrow focus on specific subgroups of non-target organisms, assuming that an absence of effect for a studied group (e.g., a model bird species such as the Japanese quail, *Coturnix japonica*) holds for the whole system (e.g., all bird species). As such, the human health impacts of pesticides have been primarily demonstrated among farmers³⁷, but recent evidence suggests increased risks of cancer, neurological disorders, and developmental issues in populations living near agricultural fields³⁸⁻⁴⁰.

All this evidence underlies the urgent need for a complex systems approach to understanding pesticide exposure pathways and developing strategies to mitigate their effects on the health of humans, non-humans, and the environment. To ensure scientific relevance and offer comprehensive insights for decision-makers and policymakers, this approach should encompass the interconnected health impacts on humans, non-humans, and the environment; integrate diverse scientific disciplines; and actively involve stakeholders and citizens in the process⁴¹.

In this paper, we present a research project designed to address the critical knowledge gaps identified above. This project, led by a multidisciplinary research team that also includes non-academics, is implemented by conducting an integrated, holistic, interdisciplinary, and transdisciplinary research study within a French agricultural landscape that is also a Long-Term Socio-Ecological Research (LTSER) platform, the LTSER site Zone Atelier Plaine & Val de Sèvre (ZA-PVS)⁴². Referred to as the *Territory Health* project, it aims to demonstrate that biota and ecosystems, far from being a menace to human health (i.e., zoonosis), can provide solutions that enhance the overall health of a region, particularly in rural areas. By fostering a deeper understanding of the relationships between biodiversity and ecosystem functioning, agricultural practices, and health, *Territory Health* seeks to promote sustainable solutions that benefit both human and environmental well-being. *Territory Health* thus adopts a complex systems perspective that simultaneously considers human, non-human, and environmental health, recognizing the validity of multiple perspectives and the interdependencies between ecosystems and social systems across multiple scales. By doing so, it aligns with various postmodern views that
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challenge the positivist, value-free objectivity of "normal" science, such as the concept of "post-normal"
science<sup>43</sup>. *Territory Health* is grounded on the EcoHealth approach, an extended version of One Health
(as defined by <sup>44</sup> and <sup>45</sup>), which emphasizes the interconnectedness of human, animal, plant, and
environmental health.

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In the following sections, we first describe the conceptual framework and basis of *Territory Health*. We then outline its main hypotheses and the various stages of its implementation, including the development of the research design and protocols, the formation of an interdisciplinary consortium, and the active involvement of citizens, local stakeholders, schools, and healthcare professionals in the research process. Next, we focus on two fundamental aspects of the project: its experimental approach and the process of building and monitoring a partnership cohort over time and across different locations. Finally, we reflect on the challenges encountered, highlighting key mistakes to avoid and precautions to consider when managing such a complex project. We also offer guidance on how similar initiatives can be replicated in other regions, emphasizing the importance of local context, stakeholder engagement, and adaptability.

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CONCEPTUAL BACKGROUND OF THE TERRITORY HEALTH PROJECT: ECOHEALTH APPROACH

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*Territory Health* is grounded in the EcoHealth approach<sup>44,45</sup>, an environmental health framework (**Box 1**). This approach is multifaceted, encompassing the co-production of knowledge, governance, social ethics and human values, gender equality, and the pivotal role of ecosystems in improving health<sup>46</sup>. More than other environmental health approaches, the EcoHealth approach raises the way we understand health as a paradigm shift, moving from a solely human-centered perspective to embrace a broader view that focuses on the relationships, interdependence, and cooperation between humans and other living organisms. From an EcoHealth perspective, biodiversity, ecosystem functioning, and nature in its broader sense are viewed as essential components by providing nature-based solutions that improve the health of all living beings. By recognizing the interconnectedness of human and ecosystem health through shared risks and solutions, *Territory Health* posits that biodiversity and ecosystems can serve as critical levers for reducing exposure to pathogens and pollutants, thereby mitigating their impacts on humans and the ecosystems. Through more effective management practices, biodiversity and ecosystems provide systemic and sustainable pathways to improving the health of all components within the socio-ecosystem, adaptive system linking human societies and ecosystem through feedbacks that shape their dynamics and resilience<sup>47</sup>. This postulate drives our research team and its partners to test hypotheses that are rooted in ecological theory, such as the dilution<sup>48</sup> or barrier effects<sup>49</sup> that result from biodiversity and landscapes. In particular, from an academic perspective regarding the wicked issue of pesticide exposure, it aims at evaluating the role of biota in the transfer of pesticides (i.e., bioaccumulation), or in their mitigation by detoxification through landscapes or soils<sup>13</sup>, as well as the role of nature for humans in decreasing pesticides' impacts on health.

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[Box 1]
152 Adopting an EcoHealth approach to promoting health in socio-ecosystems not only requires an
153 interdisciplinary approach with a systemic vision, but also a form of research based on action (action
154 research<sup>50</sup>) that actively engages both researchers and non-academic stakeholders through
155 transdisciplinary collaboration<sup>51-53</sup>. The approach adopted in *Territory Health* is interdisciplinary in that it
156 requires the knowledge and methods of several disciplines. The project team gathers researchers in
157 agroecology, ecology, ecotoxicology, plant, animal, and human epidemiology, ergonomics, public
158 health, sociology, and management sciences. Equally importantly, the approach is also
159 transdisciplinary, going beyond academic boundaries by involving non-academic stakeholders with
160 diverse and complementary expertise and roles. The project thus engages local stakeholders such as
161 local elected representatives and health practitioners and further extends transdisciplinarity by engaging
162 residents (including farmers), as well as primary school children and their teachers from the 24
163 municipalities of the ZA-PVS, in the research process. Transdisciplinarity is designed to be inclusive by
164 including non-academic actors as integral members of the project consortium. This means that the ideas
165 and actions of the research project are not solely led and implemented by a group of researchers, but
166 will emerge from a collaborative and enriched consortium that includes representatives of local
167 associations, practitioners, and territorial actors. In addition, the project's approach must have a
168 territorial dimension that emphasizes place-based research and a redefinition of human societies, where
169 non-humans are recognized as full members<sup>54</sup>. This latter perspective acknowledges the intrinsic
170 interconnection between humans, non-humans, and the environment within specific territories,
171 reinforcing the need for locally grounded approaches that respect the agency and role of all living and
172 non-living components in shaping sustainable, healthy ecosystems. *Territory Health* is thus based on
173 three key components: (i) **Nature-based solutions**<sup>55</sup>, which emphasize the co-benefits for humans and
174 ecosystems through the implementation of sustainable solutions that address long-term environmental
175 changes and risks; (ii) The **Territory**, as a political concept referring to the existence of a collective
176 deeply connected to a geographic area and united by a shared political project<sup>56</sup>; and (iii) the **Socio-ecosystem**, a complex adaptive system that highlights the interdependence and interconnectedness
177 of ecological and social systems through non-linear, feedback processes across multiple spatial and
178 temporal scales<sup>57</sup>. Thus, the project rests upon three core components: a defined territory (the ZA-PVS),
179 a collaborative group of researchers and non-academic stakeholders, and funding. The interactions
180 between these components require the implementation of adaptive management and governance<sup>58</sup> to
181 ensure that the project adapts quickly to the uncertainties and unexpected challenges that arise when
182 conducting research in real-word conditions and engaging local communities.
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184 A RESEARCH PROJECT TESTING HYPOTHESES USING A QUASI-EXPERIMENTAL
185 DESIGN TO ASSESS PESTICIDE EXPOSURE AND ITS IMPACTS AT THE LANDSCAPE
186 LEVEL

187 The *Territory Health* project has been set up in a 450 km² agricultural region in the southern part of the
188 Deux-Sèvres department (Western France), the LTSER Zone Atelier Plaine & Val de Sèvre<sup>42,59</sup> (Figure
189 1). Long-term monitoring of major components of the socio-ecosystem have been carried out for 30
190 years. Since 1994, biodiversity, ecological functions, agricultural practices, local food consumption, and
land use have been annually monitored and analyzed. The LTSER comprises 24 municipalities with populations ranging from 166 to 5,377 inhabitants⁶⁰ and nearly 400 farms, approximately 19% of which are certified organic. This extensive and continuous monitoring has yielded a rich dataset, offering both implicit knowledge of pesticide pressure—through the location of organic versus conventionally managed fields, as well as interviews conducted with farmers to obtain detailed data on pesticide treatments—and enabled in-depth analysis of long-term socio-ecological dynamics⁶¹. This makes the area a valuable living laboratory for EcoHealth research in practice, allowing researchers to analyze pesticide exposure according to the pesticide pressure and evaluate its impact on the ecosystem (biota and the environment) and human health.

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[Figure 1]

One central question in *Territory Health* investigates, in real-world conditions, the relationships between pesticide pressure in the environment and its effects on humans and non-human organisms, mediated through exposure. Addressing this question requires researchers to contrast levels of pesticide pressure at the landscape scale, thereby enabling the detection of differential impacts according to these contrasts. This quasi-experimental approach has been designed to deal with two major issues: it involves humans, and it is designed at a large scale (the territory). For these reasons, we have implemented a specific approach that is quasi-experimental in its spatial design, similar to a space-for-time substitute. This innovative experimental design is structured around two nested explicit spatial gradients of pesticide pressure, one across villages and one within villages (Figure 2). The first gradient uses the percentage of area under organic farming surrounding the village as an inverse proxy for pesticide pressure, assuming that a higher presence of organic farming corresponds to lower pesticide pressure in the landscape around the village. The second gradient considers the distance of houses within a village to the nearest conventionally farmed field, with the assumption that proximity to such fields correlates with higher pesticide exposure. Together, these two gradients allow for evaluating the relative contribution of distance (proximity to conventionally managed fields) and quantity (the mass effect of organic farming) on pesticide exposure and its effects on ecosystem and human health in rural communities. Additionally, while the statistical unit of our design is houses, our focus here is on inhabitants who also have a garden so that we can measure the impact on non-human organisms, specifically birds. Consequently, this design provides a robust analytical framework for understanding the complex relationships between pesticide use, landscape management, the degree of pesticide exposure, and the associated risks. The analyses of pesticide exposures of the environment, humans, and non-humans along the gradients will be further used to understand and quantify the links and interdependencies between environmental, human, and non-human organisms' health.

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[Figure 2]

Specifically, we focus on two main hypotheses within the quasi-experimental design. H1 posits that the diversity and quantity of pesticides detected, both in terms of total concentrations and concentrations of crop-specific molecules, is positively associated with the percentage of area under conventional farming surrounding the village and with proximity to conventional fields, reflecting either short-range drift of applied compounds or short-distance foraging behavior for birds. Accordingly, we expect the total
number of pesticides detected to be higher in villages surrounded predominantly by conventional agriculture. H2 proposes that villages with at least 20% of untreated habitats (organic farming and/or grasslands) will host higher insect and bird diversity and abundance, including a greater occurrence of rare species. This 20% threshold is supported by previous studies conducted in the LTSER ZAPVS, which showed that semi-natural habitats covering at least one-fifth of the landscape significantly enhance pollination service ⁶², and by a systematic review comprising of over 4,000 studies indicating that at least 20% to 25% habitat per km² is needed to sustain nature's contributions to people ⁶³.

## 237 MEASURING PESTICIDE EXPOSURE IN REAL-LIFE CONDITIONS

The exposome concept has gained popularity in human, animal, and plant epidemiology since it was first formalized in 2005⁶⁴,⁶⁵. The exposome is understood as the cumulative measure of environmental exposures and associated biological responses across the lifespan of an individual, including exposures from the environment, diet, behavior, and endogenous processes⁶⁶. As such, the study of the exposome is complex and presents several challenges, making it difficult to comprehensively measure the exposome across the lifespan of humans and other living organisms. In the case of pesticides, exposure levels and types vary over time based on the application schedule⁶⁷. For an accurate exposure assessment with the aim of correlating pesticide pressure with exposure levels and health, selecting appropriate measurement time points is crucial. In fact, the health effects of a given exposure can vary across different developmental periods and may be modified by synergistic or interactive effects when combined with other exposures.

In the cereal plains of western France, pesticide applications peak during two key periods: pre-sowing treatments for winter cereals (from mid-October to late November) and oilseed rape, and spring treatments (roughly from mid-March to mid-May) for all crops. From an EcoHealth perspective, pesticide exposure is assessed in humans, in living organisms (earthworms, insects, and birds, as well as pets if there are any), and in the environment (household dust, air, soil and water) during these critical periods. Both recent and long-term exposures are considered in humans and birds. While urine and feces in humans, and blood in birds offer insights into short-term pesticide exposure due to the rapid excretion of pesticides, hair in humans and feathers in birds serve as long-term biomarkers, capturing cumulative exposure over several months⁶⁸. The analysis of hair and feathers helps in understanding chronic exposure risks and provides a historical perspective on pesticide exposure⁶⁹.

Understanding exposure to complex chemical mixtures also necessitates screening a wide variety of molecules that have been applied, along with their metabolites and transformation products. In *Territory Health*, we adopt a nested approach that involves a broad screening (targeted/non-targeted screening) of more than 500 molecules, followed by quantitative assays of a predefined list of 164 molecules if detected in the first screening. This list of 164 molecules includes substances applied in the southern part of the Deux-Sèvres Department, identified using the national sales database (https://ventes-produits-phytopharmaceutiques.eaufrance.fr/), as well as molecules detected in previous studies conducted in the LTSER ZAPVS (Table S1) and those found in surface water, according to the national database (https://naiades.eaufrance.fr/bienvenue-naiades). Additionally, we included long-lived
molecules (such as lindane or dichlorodiphenyltrichloroethane (DDT)) and CMR substances (such as acetamiprid and metazachlor). The limit of detection (LOD), i.e., the lowest quantity of an exposure that can be detected by the screening method was different between matrix and molecules. For example, LOD in hair and in wipes used to collect dust varied between 0.78 and 3.12 pg/mg for hair, and between 0.01 to 0.5 ng/cm² for dust, respectively.

The human exposome is further assessed indirectly through questionnaires designed to link exposure measurements to health indicators (see below). Based on the PESTIPREV study<sup>70</sup> these questionnaires gather data on household members' characteristics (age, gender, employment, and education), the home layout (number of floors, rooms, door and window placement, and the state of renovation), dietary habits (proportion of organic food consumed), hygiene habits (housekeeping, pets, and domestic pesticide use), and outdoor activities (gardening, exercise, play, eating, and relaxing). To complement this, twice per year during spraying period (spring and autumn), residents are asked to fill out a weekly food diary during the week when urine (three samples collected on three separate days) and feces (1 sample during the week) samples are collected (with hair samples taken at the end of the week). The diary documents their meals, the provenance of food and beverages (e.g., supermarkets, local markets, or home gardens), whether the items were organically produced, and whether and how they were prepared by the residents. It also records details about outdoor activities and potential pesticide use during the week, whether being of domestic or professional use, as well as the dates of agricultural spraying in the nearby fields.

## 287 EVALUATING THE HEALTH CONSEQUENCES OF PESTICIDE EXPOSURE

In *Territory Health*, health, in its widest definition, is captured within an integrated, risk-oriented, and interdisciplinary framework applied at both individual and population or community levels for humans and birds, respectively. Environmental health is assessed through the lens of ecosystem function, focusing on the ability of soil to sustain healthy and productive ecosystems<sup>71</sup>. Soil functioning is strongly influenced by soil microorganisms through their essential role in supporting plant and animal productivity, and maintaining or improving water and air quality, hence promoting plant and animal health<sup>72</sup>. Organic matter cycling, used as a proxy for soil health<sup>73</sup>, is estimated using the tea bag index<sup>74</sup>, a method in which two types of tea bags (a green tea and a rooibos) are buried in the gardens of residents who are partners in the project. The health of the birds in these residents' gardens is assessed by measuring morphological (tarsus, beak and wing lengths, body mass, coloration of carotenoid-dependent secondary sexual characteristics), physiological (oxidative stress, antioxidant capacity), parasitic (ectoparasites, blood parasites, intestinal parasites), behavioral (vigor, aggressiveness, tonic immobility), and immune (hematocrit, leucocyte count) parameters<sup>75</sup>. Fecal analyses are also conducted to infer the birds' intestinal microbiota diversity, which plays critical roles in nutrient acquisition, immune system functioning, and detoxification processes<sup>76</sup>. This aspect is particularly relevant within an EcoHealth framework, as the connection between gut microbiota, immunity, and health in birds has parallels in humans<sup>77</sup>. Additionally, to investigate the hypothesis that birds can serve as health sentinels for humans, bird diversity is monitored in each garden through call counts (in addition to capture during mist-netting operations) within a precise radius of 100 m. Counts are performed in the morning (between
7 a.m. and 11 a.m.) twice in the breeding season (usually between April 10th and May 10th, and between May 10th and June 25th). A garden with a diverse bird community is considered a healthy environment, as such diversity reflects an abundance of food resources (insects, seeds) and suitable nesting sites for birds; birds can thus be used as proxies for human health (see below). Finally, the health of humans is assessed indirectly by analyzing the composition of human intestinal microbiota and examining the urine metabolome; both are non-invasive methods of medical diagnostics<sup>78</sup>. The composition of the intestinal microbiota is closely linked to overall health, influencing immune function, metabolism, and even mental health<sup>79</sup>. Urinary metabolites, on the other hand, serve as biomarkers for various health conditions, including neurological diseases<sup>80</sup> and cancers<sup>81</sup>, that are suspected to be associated with pesticide exposure<sup>82-83,84</sup>. The measurement of these health indicators is combined with an epidemiological study on pesticide exposure and cancer risk in humans using data from the population-based cancer registry of Poitou-Charentes. Since 2008, this Registry has been actively, continuously, and exhaustively collecting all new cancers occurring in the population living in Poitou-Charentes—regardless of where they are treated—for research and public health purposes<sup>85</sup>. The average number of new cancer cases is approximately 12,500 per year.

## A RESEARCH PROJECT THAT SETS UP A “PARTNERSHIP COHORT”

Rooted in the science of complexity, *Territory Health* recognizes that the system under study is dynamic, has non-linear properties, and is often unpredictable in regard to its trajectory. Consequently, the project has adopted a medium-term perspective spanning 10 years, with the aim of establishing a "partnership cohort" called the *Nov'Land* cohort. Inspired by medical cohorts in the traditional sense, the *Nov'Land* cohort includes humans who are monitored over the long term. However, it is distinguished by four key characteristics. Firstly, the *Nov'Land* cohort sits at the intersection of large-scale epidemiological studies and experimental controlled trials. While epidemiological studies are known for their strong statistical power due to large sample sizes, they often struggle with the potential effects of numerous covariates or confounding factors. Even when controlled for, shortcomings can persist, and only a small proportion of the variation is explained<sup>86</sup>. On the other hand, experimental studies—typically clinical trials conducted under controlled clinical conditions—generally assess the effect of a single factor in isolation. While this approach allows for a clear causal inference, it lacks realism, as it is removed from the complexity of real-world conditions. In the *Nov'Land* cohort, we combine the strengths and weaknesses of both approaches by integrating the realism of multiple exposure sources using a quasi-experimental design using a two-gradient approach to capture an accurate and comprehensive understanding of pesticide exposure. Secondly, the *Nov'Land* cohort is spatially explicit, considering and leveraging the heterogeneity of the territory—such as the varying proportions of organic farming in the landscape—to contrast different exposure scenarios (**Figure 2**). Thirdly, the *Nov'Land* cohort allows us to monitor how solutions aimed at reducing pesticide pressure and exposure actually affect pesticide exposure and its consequences. The territory of the cohort is also a research infrastructure where socio-ecological experiments have been carried out with and by farmers to promote the agroecological transition, testing solutions for reducing pesticide use in real-world conditions, while maintaining production, economic performance, and biodiversity<sup>87,88</sup>. In addition, actions have been taken with inhabitants to increase the
amount of food consumption from local organic farming<sup>89</sup>. Furthermore, within *Territory Health*, a series of targeted interventions has been thought to transform food consumption practices, foster capacity building, and improve the health of the territory (detailed in the next section). As a result, the *Nov'Land* partners—whether they be farmers or non-farming inhabitants—are expected to actively modify their environment through changes in agricultural production practices, diets, and behavior. Fourthly and finally, the *Nov'Land* cohort includes non-human species, specifically the birds in residents' gardens. Birds are of particular interest because they share their environment with the inhabitants, living in the same gardens, and as many health-related parameters can be measured in birds to assess the impact of various pesticide exposures. Moreover, our project will explore the extent to which garden-foraging or -dwelling birds can serve as sentinels of human health. The underlying reasoning is that a garden rich in birds serves as an indicator of a healthy, thriving environment, with the consequence that the human inhabitants of such gardens will likely also enjoy better health. As members of the cohort, birds can thus act as early warning signals for both environmental and human health risks. If our hypotheses are confirmed, this could provide inhabitants with a means of improving their gardens' health—by offering more and healthier resources to birds—as well as a tool for monitoring the effects of changes in garden management, such as through birdsong patterns.

Overall, the *Nov'Land* cohort monitors and measures how shifts in landscape, time, and the practices of its members will modify the impact of pesticide use and exposure on health across individuals (humans and birds), collectives, and landscapes. "Practices" are considered in a wider sense, being related to food production and consumption, diet, garden and housekeeping management, and the environment within which each member of the cohort lives. What makes the *Nov'Land* cohort particularly innovative is its focus on the diverse sources of pesticide exposure, whether through food or environmental pathways, while also being experimental and explicitly integrating human-nature relationships. The cohort adopts a pluralistic and inclusive approach, encompassing all inhabitants of the ZA-PVS—humans who are not necessarily patients, but everyday residents, including farmers—and non-humans, alongside their shared environment (specifically the gardens). The ultimate aim is for the *Nov'Land* cohort to encompass all 34,000 residents of the area.

## 373 CREATING A TERRITORIAL DYNAMIC TO IMPROVE HEALTH IN THE TERRITORY

The challenge lies not only in characterizing these changes and their impact on human and ecosystem health through the existence of the cohort, but also in assessing the wider implications for the trajectory of the socio-ecosystem under study and understanding whether these changes ultimately contribute to more sustainable practices and healthier communities and environments. This raises the question of how to characterize the trajectory of the socio-ecosystem and, in particular, how to assess its overall health, as well as the health of its individual components. In *Territory Health*, we aim to co-design a set of indicators—ecological, health, social, and economic—with the cohort partners to provide critical insights into animal and human well-being, ecosystem functioning, economic viability of economic actors (such as farmers), species diversity, and so forth.

*Territory Health* seeks to identify novel solutions that enhance health by actively involving diverse stakeholders in structured, deliberative learning and decision-making processes. It is grounded in a
collaborative adaptive management framework<sup>90</sup> that integrates multiple perspectives and knowledge sources to minimize uncertainty and promote a shared understanding of ecosystem dynamics and management outcomes. The project therefore promotes the participation and collaboration of inhabitants and stakeholders, not only by monitoring pesticide exposure and its health effects but also through a series of targeted interventions. Our approach expands a strategy that has been conceptualized and implemented for more than ten years in the LTSER ZAPVS <sup>89</sup>. Our strategy combines what we call *background actions, targeted actions and transformative actions* (Figure 3). While *background actions* are carried out across the entire LTSER ZAPVS area, *targeted actions* take place only in the villages where the research program is implemented.

[Figure 3]

The *background actions* aim to build trust in the research process, in science, and among participants, thus facilitating citizen engagement in the research process. For example, we take part in local markets or community events to introduce the program to residents and to gather their perspectives on health, as well as on the roles of biodiversity and ecosystems (Figure 3A). We also communicate through electronic letters that are sent to approximately 2,000 inhabitants of the LTSER ZAPVS (four to six letters per year).

The *targeted actions* encompass, in targeted villages, a range of research and intervention activities designed to generate actionable knowledge on the interconnections between human health, biodiversity, and the environment; while no such activities occur in the other villages of the LTSER ZAPVS allowing for comparison. Within this framework, the *Territory Health* project is presented to health professionals or municipal councils during dedicated meetings. In addition, the members of our consortium, comprising associations, NGOs, and farmers' cooperative enterprises, collaborate with schools and high schools to address the "Agriculture-Food-Environment-Health" nexus. Four separate interventions address each of these themes individually, before bringing the scholars together to reflect and create projects that connect all four themes, emphasizing their views on the interdependencies between human health, biodiversity, and the environment (Figure 3B). Since 2023, a total of six schools, representing about 900 children between 5 and 11 years of age, have taken part in these interventions. In high schools, the interventions are designed to empower teenagers to act to improve health within the framework of the EcoHealth approach. In this context, the high school is envisioned as a territory, and the interventions aim to empower the scholars to develop projects that enhance its overall health. In addition, meetings are organized to foster social interactions and engagement within a reflexive process, while establishing relationships, strengthening collaborative capacity, promoting social learning and identifying local leaders. These meetings seek to gather inhabitants and stakeholders from diverse backgrounds, knowledge, and experiences, who may have differing concerns about health and the risks related to pesticide exposure. Participants include local residents, farmers, healthcare professionals (including practitioners, pharmacists, and nurses), decision-makers, and representatives from local NGOs, ensuring a balanced and representative mix of local and regional stakeholders. Building on previous transdisciplinary projects<sup>91</sup>, the *Territory Health* project emphasizes knowledge exchange, knowledge generation, and social learning<sup>92</sup> to strengthen adaptive capacity through cooperation
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between scientists and participants. To support this process, scientists share and discuss the data and insights they have gathered on local pesticide exposure, its health effects, and the potential factors that may mitigate or amplify exposure (including the roles of biota and ecosystems). For example, public disseminations of pesticide exposure results were organized in summer 2025 in the villages, in the presence of cohort members, others residents and local elected representatives (Box 2). These events each brought together from 40 to 70 participants and provided a first space for questioning potential individual and collective solutions to reduce pesticide exposure.

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Building on these discussions, *transformative actions* will be carried out to design transformed practices and indicators to assess the efficiency of these practices to improve health (Figure 3C). Examples of such transformations could be a reduction in the use of pesticides by farmers, an increase in the consumption of organic food by local inhabitants, or a change in garden management to increase biodiversity, especially of bird species. Although the final methodology has not yet been decided, we are considering approaches such as scenario analysis, strategic foresight and speculative fiction, back casting and scenario-building ⁹³,⁹⁴, complemented by participative tools such as forum theatre ⁹⁵ or participatory prospective analysis ⁹⁶. These methods enable participants to share visions of a desirable future for their territory and identify common unknowns. Workshops will be documented and transcribed for thematic analysis, combining both inductive and deductive approaches with explicit reference to the Territory Health conceptual framework (see ⁹⁷ for an example based on the analysis of farmers’ surveys). Evaluation will rely on surveys to assess the processes of knowledge co-production, the diversity of participation, and the range of ideas generated, complemented where relevant by pre- and post-tests to examine changes in perceptions or knowledge.

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By connecting diverse communities and sharing knowledge over time and across the boundaries of stakeholder organizations, the overall interventions will contribute to building a knowledge infrastructure: a substrate supporting how the issues are conceptualized and acted upon⁹⁸. Its ability to enhance the processes of knowledge creation and integration related to improved health at multiple scales (from the individual to the territory in an EcoHealth Perspective) to achieve the required transformed practices will be evaluated by social scientists.

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## IMPORTANT ISSUES IN CONDUCTING ECOHEALTH RESEARCH, AND SUGGESTED GUIDANCE

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### Ethical considerations

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The first two years of the project were devoted to developing and drafting research protocols for submission to the relevant ethics committees. These steps are essential to ensuring the ethical integrity and scientific rigor of the project. For birds, the protocols were submitted to the Comité d'Ethiques en Expérimentation Animale (CE2A) and the Centre de Recherches sur la Biologie des Populations d'Oiseaux (CRBPO), which ensures that the study meets ethical standards for the treatment and monitoring of wild bird populations. Authorization for the proposed bird health monitoring procedures was obtained in 2023 for 20 bird species. All procedures involving birds prioritize animal welfare, ensuring that the birds are not subjected to undue stress, injury, or death throughout the study. For humans, the protocols were submitted to the Comité de Protection des Personnes (CPP), which reviews
and approves research involving human subjects to protect their rights, welfare, and privacy (including personal data protection). The ethical approval process for the proposed studies on humans was more challenging due to the innovative nature of the research project, which differs significantly from conventional clinical trials. This led to some initial misunderstandings (e.g., the members of the partner cohort are not patients suffering from a disease for whom we are seeking explanatory factors.) and necessitated adjustments and clarifications to align our protocol with the requirements of the CPP, whilst maintaining the aims of our research. Despite these challenges, only minor changes were required and the project received approval in June 2024.

Since its set up, the project is responsibly run. Informed consent is obtained from all participants. Data are pseudo-anonymized to protect participant privacy, and individual results are returned directly to participants by the field investigators, who conduct the surveys and collect the various samples. Researchers responsible for data analysis do not have access to participants' identities.

## Data integration and analysis

Since 2023, over 6,000 samples of human, non-human and environmental matrices have been collected (Table 1), generating diverse datasets encompassing human, non-human, and environmental exposure measures, survey data, and health records. To ensure interoperability, each sample was assigned a unique identifier beginning with the housing code. Data analysis follows a "pressure-exposure-impact" framework (Figure 4). In the first step, pesticide pressure, which is approximated by landscape parameters (percentage of area in conventional farming) and pesticide sales or applications, is linked to exposure levels (Figure 4A). Exposure is quantified either as the number of detected molecules or total concentrations using Generalized Linear Models (GLMs) or Generalized Linear Mixed Models (GLMMs, when multiple samples of a given matrix were collected); or through multivariate analyses assessing pesticide profiles. The second step investigates the relationship between human, non-human and environmental exposure, for example, by exploring the correlations between dust, bird and urine pesticide exposures (Figure 4B). Here, GLMs are used when evaluating species richness or diversity, while multivariate approaches such as k-table methods, explore how exposure profiles shape microbiota community structure. The third step explores the entire pressure-exposure-impact chain using structural equation modelling, assessing how pesticide pressure affects health outcomes indirectly through its influence on exposure (Figure 4C). All steps incorporate relevant covariates into the statistical models and, where appropriate, apply predictive gradients (e.g., the percentage of area under organic farming as a potential mitigating factor for exposure) to evaluate the robustness of observed associations. The strength of this approach relies on both the size of the dataset and the availability of high-quality covariate information, including socio-economic and geographic characteristics.

## Recruiting participants and partners

The success of *Territory Health* largely depends on effective recruitment, achieved through a multimodal approach. To maximize recruitment success, we combine passive methods such as flyers and newsletters—in some cases, some of which are distributed by municipality staff—with direct strategies that involve person-to-person interactions. The studies conducted by the research team in the LTSER ZAPVS since 1994 have played a key role in building community relationships and fostering trust and
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credibility, which are essential for successful participation in research⁵⁹. In addition, a significant proportion of the LTSER ZAPVS population is interested in the research topic and eager to gain a deeper understanding of pesticide exposure in their environment. For the pesticide exposure study, the sample size was set at 20 households per target village to ensure both a sufficiently large sample for accurate data analysis and practical ease of sample collection and analysis. The inclusion criteria also accounted for the distance of each household from the nearest conventional arable field, and required garden characteristics allowing bird health assessment, socio-economic factors representative of the village population (such as age, occupations), and for the study cohort to be composed of at least 10% agricultural workers. Only LTSER ZAPVS residents aged 18 years or older who are willing and able to give informed consent are considered eligible. Inhabitants who are interested but either do not fit the inclusion criteria or are too busy to participate in the pesticide exposure study are invited to attend workshops on designing solutions for reducing pesticide exposure and on indicators of health and well-being.

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Maintaining participants within the cohort

Maintaining participants within the *Nov'Land* cohort over time will be challenging. We have therefore developed a strategy that combines communication, capacity building, trust-building relationships, and invitations to increase participants' involvement in the research project. A member of the consortium is the dedicated contact person for the cohort participants. This person is in charge of making appointments for data collection, conducting the surveys, inviting the participants to research-centered events and answering any specific questions the participants may have on the research. To avoid disturbing participants in their daily lives, we prefer to contact them by text messages. To foster a sense of inclusion in the research process, we produced a booklet for the cohort members. The booklet presents the aims of the project and provides a detailed explanation of its methodology. A portion of the booklet is reserved for the documentation of research outcomes - including but not limited to bird diversity, results of pesticide exposure measurements, and home-range movements of domestic cats -, giving participants a clear understanding of how their contributions are being used. In addition, the booklet includes a feedback section that encourages participants to share their thoughts, experiences and suggestions, promoting active engagement and facilitating improvement of the research throughout the project. Cohort members are also invited to attend seminars in which the project's initiatives and achievements are presented. These events provide an opportunity for members to meet other members in the cohort and speak with the researchers, fostering a collaborative atmosphere. They are also encouraged to contribute to workshops involving other residents, health professionals, and local elected officials. These workshops focus on co-designing the indicators that will be used to characterize the trajectory of the socio-ecosystem, ensuring that the indicators reflect the shared goals and concerns of the local population. This strategy has proven to be effective, as only six among the 214 participants have dropped out since the start of the project: two due to relocation, one due to health issues, and three due to changes in their availability for participation.
539 **CONCLUSION**

540 Improving the health of humans, non-human organisms, and the environment requires a dedicated effort
541 to fully understand the interrelationships between various causal factors of poor or good health, and to
542 develop solutions that consider the multidimensional, interrelated, and dynamic nature of these factors.
543 Rooted in the EcoHealth perspective, the *Territory Health* project addresses this challenge by adopting
544 whole-system thinking and a transdisciplinary approach with the goal of building the capacity of local
545 inhabitants (whether they be farmers, consumers, health practitioners, or students) to create knowledge
546 and hence build a knowledge infrastructure.

547 Part of this knowledge emerges from our innovative quasi-experimental design, which enables
548 hypothesis testing on the relationships between pesticide pressure, exposure, and health impacts.
549 Preliminary results on pesticide residues in household dust support our first hypothesis: the number of
550 pesticide molecules detected in dust increases with the proportion of conventional crop types in the
551 surrounding landscape (Box 2). Discussions of these findings during public dissemination workshops in
552 summer 2025 were particularly encouraging: almost all participants engaged actively in the dialogue,
553 many already seeking practical solutions to reduce pesticide exposure.

554 These preliminary results and participatory exchanges demonstrate the value of such projects in
555 reshaping science-society relationships and developing fundamental alternative practices that enhance
556 the overall well-being of humans, non-human organisms, and the environment, and ultimately create a
557 more sustainable, resilient, and inclusive socio-ecosystem system. The *Territory Health* project holds
558 promise for informing regional public policies such as the Nouvelle-Aquitaine region roadmap NéoTerra
559 (https://www.neo-terra.fr/) and the Regional Health-Environment Plan (PRSE4, https://www.nouvelle-
560 aquitaine.ars.sante.fr), both of which promote agroecology, healthy diets, and a One Health perspective.
561 If successful, this model could be replicated in other regions to generate locally grounded knowledge
562 and identify concrete levers for reducing chemical exposures and fostering healthier socio-ecological
563 systems.

564 **AUTHOR CONTRIBUTIONS**

Conceptualization, S.G. and V.B.; methodology, S.G., V.B., J.M., S.L., and R.T.; writing—original draft, 565 S.G.; writing—review & editing, all authors; funding acquisition, S.G., V.B., and J.M.; supervision, S.G. 566

567 **DECLARATION OF INTERESTS**

The authors declare no conflicts of interest.

569 **DECLARATION OF GENERATIVE AI AND AI-ASSISTED TECHNOLOGIES**

During the preparation of this work, the authors did not use generative AI.

571 **ACKNOWLEDGMENTS**

572 We gratefully acknowledge the participation of the "habitants-partenaires" in the research. We thank
573 Audrey Bailly, Antonin Chesneau, Etienne Debenest, Jean-Luc Gautier, Roxane Hertz, Swann
Heuveline, and many students and field workers for excellence in conducting surveys, developing methodology, organizing workshops and restitutions, and data collection. We are also deeply grateful to our non-academic partners: the Groupement Ornithologique des Deux-Sèvres, the APIEEE, the Roseaux Sociaux, and the SCOP Wision. We are also grateful to the mayors and councilors of the communities where the project has been implemented for their support and help in recruiting "habitants-partenaires."

## 580 FUNDING

This work was supported by the Région Nouvelle Aquitaine (projects Nov'Land "Territoire en transition pour améliorer la santé des sociétés et des écosystèmes et la résilience alimentaire" and Together "Concilier agriculture et riverains en territoire rural en réduisant l'utilisation des pesticides et en améliorant la santé des écosystèmes"), INRAE Metaprogramme Metabio (through the cofounding of Audrey Bailly's PhD thesis), and SIRIC BRIO (through the cofounding of Frederic Ouédraogo's Post-Doctorate role). This research was funded, in part, by the Agence Nationale de la Recherche (ANR), grant PHYTOBIRD « ANR-24-CE34-1471-01 ». Action under Ecophyto II+ plan, led by the Ministries of Agriculture, Ecology, Health and Research, with financial support of the French Office for Biodiversity for the projects ALL-HEALTHY "Opérationnaliser le concept "une seule santé" par la recherche-action pour comprendre les liens entre exposition aux pesticides et santé d'un territoire" and NIEPCE " Conception d'un cadre méthodologique visant à l'élaboration d'un panel d'indicateurs précoces d'impacts de l'exposition aux pesticides sur la santé globale d'un territoire ". This work is part of the SOLU-BIOD project (Living-Lab 2.Sèvres) of the French national research program on nature-based solutions, and has benefited from a government grant operated by the French National Research Agency as part of the France 2030 program, reference ANR-22-EXSO-0002. SG is funded by INRAE.

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913 **BOX 1 – CONCEPTS FOR A UNITED VIEW OF HEALTH**

914 Several concepts fall under the broad umbrella of environmental health, including the One Health⁹⁹,
915 Planetary Health¹⁰⁰, and EcoHealth¹⁰¹ frameworks. These approaches collectively represent a paradigm
916 shift in our understanding of health, moving from a solely human-centred perspective to a broader
917 paradigm that integrates the health of humans with that of their environment. All of these concepts rely
918 on a holistic approach that links humans, animals, plants, and the environment (including water and air),
919 recognizing that their states of health are interdependent. However, they differ from one another—
920 sometimes in subtle ways, sometimes more profoundly—in how these relationships are defined and
921 explicitly considered. The differences primarily stem from the relative emphasis placed on human health
922 versus other components of health, as well as the role and importance attributed to non-human
923 organisms. The One Health concept primarily focuses on the interconnectedness of human, animal, and
924 environmental health, with an emphasis on zoonotic diseases and health systems¹⁰². In contrast,
925 Planetary Health broadens this perspective, addressing the interplay between human health and the
926 state of Earth's natural systems, emphasizing the sustainability of those systems for future
927 generations⁹⁹. In the *Territory Health* project, we specifically refer to the EcoHealth concept, as we
928 believe biodiversity and ecosystems play multiple critical roles in human health and well-being. These
929 roles have been explicitly acknowledged, quantitatively analyzed, and actively promoted¹⁰³.

930 **BOX 2 – FIRST FINDINGS FROM HOUSEHOLD DUST AND CITIZEN FEEDBACK**

931 Between July and September 2025, five meetings were organized between scientists from the *Territory Health* program and residents of the LTSER ZAPVS to present and collectively discuss the first results
932 on pesticide exposure from dust samples collected in four villages monitored in 2023 (two) and 2024
933 (two) **(Figure Box 2A)**. Four of these meetings were held in collaboration with the municipal councils
934 and took place in community halls, while the fifth was hosted at the research laboratory and targeted
935 healthcare professionals and agricultural stakeholders. Attendance ranged from 40 to 70 participants
936 per event, and the presentation of results lasted approximately one hour.
937

938 The figure below (Figure Box 2B) shows a first result: the number of pesticide molecules quantified in
939 dust samples from 77 households increased with the proportion of area in conventional farming within
940 a 1,500 m radius around each village. The presentation of these preliminary findings sparked extensive
941 discussion—almost all participants actively engaged in the exchange, and many were already seeking
942 practical ways to reduce pesticide exposure. Among the actions mentioned were banning domestic
943 pesticide use for mosquito control, finding alternatives to flea collars containing neonicotinoids for pets,
944 and increasing the consumption of local and organic food products. Workshops will be organized in
945 autumn 2025 to continue these reflections, with the aim of generating ideas for individual and collective
946 actions to reduce pesticide use and exposure.
947

[Figure Box 2]
948 FIGURE TITLES AND LEGENDS

949 **Figure 1. Location of the study site and its spatial organic farming distribution.**

950 (A) Map of the study site, Long Term Socio-Ecological research site Zone Atelier Plaine & Val de Sèvre, which is a rural territory in western France. Green areas represent fields under organic farming. (B) Location of the study site on the French map. Each yellow spot shows arable fields.

953 **Figure 2. Schematic representation of the transdisciplinary and quasi-experimental approach, based on a double gradient of pesticide pressure, to assessing pesticide exposure and its consequences on health within the Long Term Socio-Ecological research site Zone Atelier Plaine & Val de Sèvre (ZAPVS).**

957 The *Territory Health* project uses a "pressure-exposure-impact" chain. In the right upper corner: the colored square shows a schematic representation of the landscape around the villages within the ZAPVS in which the amount of organic farming varies from 0 to 99% (within 1 km²). Colored squares represent landscape pesticide pressure around villages (from low (green) to high (red)). In each village, sampling is performed in houses and gardens distributed along a gradient of distance to the nearest conventionally managed field. On the bottom left, the box presents the matrices sampled to assess pesticide exposure in humans (feces, urine, hair), biota (earthworms, insects, birds, and cats), and the environment (dust, water, soil). Questionnaires are also conducted to collect data on the potential factors influencing pesticide exposure. All samples are analyzed to detect and quantify pesticide residuals. Health is assessed through proxies such as the human microbiome, soil organic matter recycling, and bird species diversity and life history traits (upper right part of the figure).

968 **Figure 3. Strategy to foster a territorial dynamic for improving population health.**

969 The strategy combines background actions (A), targeted actions (B), and transformative actions (C). Background actions are implemented across the entire LTSER ZAPVS area, while targeted actions focus on the villages involved in the research program. (A) Examples of background actions: a stand at a local market and participation in the Science Festival (*Fête de la Science*). (B) School interventions where children created posters illustrating their understanding of One Health and its links with biodiversity and ecosystems. Two posters produced during the June 2024 closing days are shown. (C) Workshops will engage participants in sharing visions of a desirable territorial future and identifying common uncertainties.

977 **Figure 4. Examples of data analyses conducted within the Territory Health project in primary schools.**

979 Data analyses follow an integrated "pressure-exposure-impact" conceptual framework. (A) The number of molecules detected or the total concentrations quantified in urine are modeled using a generalized linear model (GLM) as a function of variables representing pesticide pressure, such as landscape elements and pesticide use. The model also includes covariates such as diet during the urine collection week and socio-economic factors (e.g., occupation, sex, age). (B) Multivariate analyses are used to explore correlations between pesticide profiles in humans, biodiversity, and/or environmental samples collected at the same sites. Depending on the analysis type, variables serving as proxies for pesticide
pressure can also be included. (C) The effects of pesticides on bird health are quantified using a
structural equation model that integrates the relationships between pesticide pressure (landscape,
pesticide use), pesticide exposure in the environment and preys, and bird exposure. This approach
allows both direct and indirect effects of pesticide exposure on bird health to be assessed.
Table 1. Number of samples collected per village and matrix. Samples were collected in villages A and B in 2023, villages C and D in 2024 and villages E and F in 2025. Bird sampling was conducted in a subset of households which had gardens suitable for bird surveys. The number of households, in which bird sampling was performed, is indicated in parentheses next to the number of blood samples and behavioral measurements.

<table><thead><tr><th></th><th></th><th>A</th><th>B</th><th>C</th><th>D</th><th>E</th><th>F</th><th>Total</th></tr></thead><tbody><tr><td rowspan="4">Human</td><td>Hair</td><td>31</td><td>28</td><td>26</td><td>26</td><td>26</td><td>29</td><td>102</td></tr><tr><td>Urine</td><td>93</td><td>84</td><td>81</td><td>87</td><td>84</td><td>103</td><td>489</td></tr><tr><td>Feces</td><td>28</td><td>23</td><td>21</td><td>25</td><td>21</td><td>29</td><td>149</td></tr><tr><td>Feces - Microbiote<sup>2</sup></td><td>28</td><td>24</td><td>21</td><td>26</td><td>22</td><td>29</td><td>149</td></tr><tr><td rowspan="4">Biodiversity</td><td>Earthworm</td><td>34</td><td>30</td><td>17</td><td>26</td><td>13</td><td>16</td><td>106</td></tr><tr><td>Insects</td><td>19</td><td>21</td><td>21</td><td>21</td><td>20</td><td>21</td><td>126</td></tr><tr><td>Birds - blood</td><td>~400(10)</td><td>~400(10)</td><td>~350(8)</td><td>~350(8)</td><td>~400(10)</td><td>~400(10)</td><td>~2300</td></tr><tr><td>Birds - behavior<sup>2</sup></td><td>>380(10)</td><td>~400(10)</td><td>~350(8)</td><td>~350(8)</td><td>~400(10)</td><td>~400(10)</td><td>~2300</td></tr><tr><td rowspan="5">Environment</td><td>Cat Hair</td><td>18</td><td>22</td><td>14</td><td>16</td><td>7</td><td>12</td><td>66</td></tr><tr><td>Air<sup>1</sup></td><td>2</td><td>1</td><td>2</td><td>1</td><td>2</td><td>2</td><td>10</td></tr><tr><td>Dust</td><td>123</td><td>117</td><td>63</td><td>66</td><td>60</td><td>63</td><td>375</td></tr><tr><td>Soil</td><td>64</td><td>61</td><td>34</td><td>35</td><td>34</td><td>35</td><td>125</td></tr><tr><td>Water</td><td>53</td><td>53</td><td>41</td><td>31</td><td>26</td><td>20</td><td>124</td></tr><tr><td></td><td>Tea-Bag<sup>2</sup></td><td>204</td><td>196</td><td>204</td><td>201</td><td>146</td><td>166</td><td>552</td></tr></tbody></table>

<footnote n="1">¹ Started in summer 2025</footnote>

<footnote n="2">² Proxies of health</footnote>
(A)

<figure><img src="image_3.png" /></figure>

ZAPVS

Organic farming

(B)

<figure><img src="image_4.png" /></figure>

France

<figure><img src="image_5.png" /></figure>

Other

<figure><img src="image_6.png" /></figure>

Cropland

<figure><img src="image_7.png" /></figure>

Grassland

<figure><img src="image_8.png" /></figure>

Forest

<figure><img src="image_9.png" /></figure>

Vineyard/Orchard

<figure><img src="image_10.png" /></figure>

Urban (artificial)

<figure><img src="image_11.png" /></figure>

<figure><img src="image_12.png" /></figure>

Zones
Ateliers

LYON FRANCE

PLAINE ET VAL DE DEVRE

<figure><img src="image_13.png" /></figure>

<figure><img src="image_14.png" /></figure>
## SELECTION OF VILLAGES & INVOLVEMENT OF INHABITANTS

<figure><img src="image_15.png" /></figure>

<figure><img src="image_16.png" /></figure>

<figure><img src="image_17.png" /></figure>

Personal information
Habits

Food consumption
House characteristics

<figure><img src="image_18.png" /></figure>

Hair + GPS

<figure><img src="image_19.png" /></figure>

Distance to the
nearest conventional
field

Inhabitants-Partners

PRESSION

EXPOSURE

IMPACT

<figure><img src="image_20.png" /></figure>

<figure><img src="image_21.png" /></figure>

<figure><img src="image_22.png" /></figure>

<figure><img src="image_23.png" /></figure>

<figure><img src="image_24.png" /></figure>

Microbiome

<figure><img src="image_25.png" /></figure>

<figure><img src="image_26.png" /></figure>

Life history traits

Behavior

Physiology

Reproduction

<figure><img src="image_27.png" /></figure>

Bird species diversity

<figure><img src="image_28.png" /></figure>

Soil functioning

Organic Matter Cycling

## ANALYSIS OF PESTICIDE RESIDUALS

Screening of 500 molecules (detection)

Specific research on 105 molecules (quantification)

<figure><img src="image_29.png" /></figure>

<figure><img src="image_30.png" /></figure>

<figure><img src="image_31.png" /></figure>

<figure><img src="image_32.png" /></figure>

<figure><img src="image_33.png" /></figure>

Zones
Ateliers

LTSEF FRANCE PLAINE ET VAL DE SEVRE

<figure><img src="image_34.png" /></figure>
(A)

Background actions

Entire LTSER ZAPVS

To build trust in the process, in science,
establishing relationships,
strengthening collaborative capacity

<figure><img src="image_35.png" /></figure>

Discussion on the role of insect pollination for
human health during a Science Festival (oct-25)

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(B)

Targeted actions

To generate actionable knowledge on the
interconnections between human health,
biodiversity, and the environment

<figure><img src="image_37.png" /></figure>

Santé = HEALTH

<figure><img src="image_38.png" /></figure>

(C) Transformative actions

In villages in which the program is implemented

To design transformed practices and
indicators to assess the efficiency of
these practices to improve health

Interventions in schools and high schools to address
the "Agriculture-Food-Environment-Health" nexus

<figure><img src="image_39.png" /></figure>

<figure><img src="image_40.png" /></figure>
<figure><img src="image_41.png" /><figcaption>(B) Relationships between Human, Biodiversity and Environmental exposure</figcaption></figure>

<figure><img src="image_42.png" /><figcaption>(C) Relationships between pesticides pressure, exposure and impact</figcaption></figure>

<figure><img src="image_43.png" /></figure>

<figure><img src="image_44.png" /></figure>