Homo sapiens appeared roughly 300,000 years ago. As outlined in naturalist Charles Darwin’s book On the Origin of Species, this long transition occurred through continuous evolutionary pressures, shaped by interactions with surrounding microbial communities and natural environments. As species struggled and evolved within their ecosystems over time, natural selection shaped not only their physical traits but also their internal immune system. This evolutionary process equipped organisms with a sensitive and a complex system to combat pathogens and foreign agents encountered in their natural environments. Ultimately, it is fair to say that human existence is the direct product of nature shaping our biology.

The long-standing relationship among humans, microbes, and their shared environment was double-edged, yet they complemented each other. However, driven by rapid urbanisation and shifting lifestyles, human populations are slowly becoming disconnected with nature. Extensive scientific research and data collection have demonstrated the adverse effects of this ecological disconnect on the human immune system, particularly among recent generations of children, in the form of immune-mediated inflammatory diseases (IMIDs).

Multiple factors impact inflammatory diseases

Over the past two decades, the rising incidence (new patients) of immune-mediated inflammatory diseases (IMIDs) has drawn increasing attention from global researchers and policymakers. These are heterogeneous groups of inflammatory pathologies of multifactorial etiology (conditions caused by multiple factors) and involve either simultaneously or sequentially more organs. Some of the common examples are Crohn’s disease, ulcerative colitis, psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis, psoriasis, multiple sclerosis, type 1 diabetes, and asthma.

Unlike diseases caused by infectious agents, IMIDs are multifactorial in origin and arise through interactions among genetic susceptibility, environmental exposures, lifestyle factors, and immune dysregulation. The epidemiology of these diseases is thought to be closely associated with rapid urbanisation, change in lifestyles, industrialisation, and reduced exposure to natural environmental factors according to a 2010 overview of studies of the incidence, prevalence, natural history, and comorbidities of IMID.

As these changes occur at different rates across countries and regions, substantial geographic variation in disease incidence and prevalence has been observed. It has also been observed that the burden of IMIDs is often reported following periods of industrial development and urban growth, suggesting that environmental and lifestyle transitions may play an important role in disease emergence.

Developing immune tolerance

This commentary focuses on immune tolerance alone in the broad umbrella topic of immune maturation and development. The immune system of a child is still immature after birth, and it continues to mature through interactions with the surrounding environment and microbes from infancy (0-12 months) through early childhood, approximately one to five years of age. During infancy and childhood, the body produces millions of immune cells with receptors generated at random. New immune cells continue to develop throughout life, although new T-cell production is the highest during infancy and early childhood. It is during this stage that the immune system learns what to attack and when not to attack, a process known as immune tolerance. This involves mechanisms that help regulate immune responses to substances encountered throughout the body and environment. These mechanisms strengthen peripheral tolerance, teaching the immune system that many antigens, from commensal microbes to pollen and food proteins, are not threats.

In allergic diseases (including atopic asthma, hay fever, atopic dermatitis, food allergy), and other immune-mediated inflammatory diseases, this balance is disrupted. Instead of strong regulatory control, the immune system skews toward inflammatory pathways.

Just as we cannot learn to swim without getting into the water, how is the immune system supposed to learn tolerance without sufficient exposure? It needs “training data,” and an inevitable part of that comes from microbial diversity: the trillions of microbes that live on our skin, in our gut, and in the air we breathe. This connection between the natural environment and immune system development has been recognised by scientists for more than three decades. It has been studied against the backdrop of the increasing burden of allergies and other immune-mediated inflammatory diseases (IMIDs).

Over time, different hypotheses have evolved to explain this relationship. The Hygiene Hypothesis, first proposed in the late 1980s, suggested that reduced exposure to infections during childhood was associated with a higher risk of allergic diseases. As research progressed, this idea matured into the Old Friends Hypothesis, which argued that what matters most is not infections per se, but the loss of harmless microbes that co-evolved with humans, our “old friends”. More recently, the Biodiversity Hypothesis has broadened this perspective by linking human health directly to environmental biodiversity. It proposes that contact with diverse natural environments enriches the human microbiome and supports balanced immune regulation. The causal link between nature and the human immune system development is still being investigated, and a great deal of research is currently being conducted across the globe.

As of now, the available evidence points in the direction that the further we move away from nature, and the greater the ecological disconnect a child experiences, the higher the price they may pay in the form of immune dysregulation, potentially leading to lifelong immune-mediated inflammatory diseases (IMIDs).

Reconnecting children, cities and nature in India’s urban future

Urbanisation and economic development are inevitable aspects of a growing nation, and India is no exception. According to the World Bank, India has witnessed substantial urban expansion over the past decade. Urbanised regions are often associated with better infrastructure, improved living standards, and greater access to employment opportunities. As a result, people tend to migrate toward urban centres.

Also, because urban areas contribute more significantly to the economy, governments often seek to develop smaller towns into semi-urban or urban centres to distribute growth and opportunities more evenly across the country. However, the extent of urbanisation continues to expand across India. While urban development is essential for economic progress, inadequate urban planning can disrupt natural ecosystems and compromise the surrounding environment. Although people generally perceive urbanised and developed regions as offering better healthcare and improved living conditions, rapid urbanisation can also introduce lifestyle changes that negatively impact health. Reduced exposure to natural environments, changes in dietary patterns, increasing pollution, and sedentary lifestyles have all been implicated in altering immune system development and function.

Several epidemiological studies from developed countries have shown that the rise in immune-mediated inflammatory diseases (IMIDs) often coincides with periods of rapid industrialisation and urbanisation. As India continues to develop, this represents a critical opportunity to monitor emerging trends in IMID burden across its population.

According to a recent Lancet publication, the incidence of immune-mediated inflammatory diseases (IMIDs) has been increasing in India. While the exact causes of IMIDs are multifactorial and remain incompletely understood, one of the leading explanations is the reduced exposure to the natural environment during critical stages of immune system development in childhood. Concepts such as the Old Friends Hypothesis and the Biodiversity Hypothesis have gained significant attention in this regard. Today’s children may be at a greater risk of immune dysregulation due to rapid environmental and lifestyle changes, including the loss of natural ecosystems, reduced outdoor exposure, increasing urbanisation, and shifts in lifestyle patterns.

While families can play an important role at the individual level, policymakers and urban planners also have a responsibility to create environments that support public health. Urban planning strategies that prioritise green spaces, parks, tree cover, and access to natural environments can help promote healthier and more sustainable communities. Evidence suggests that well-designed urban environments may contribute not only to improved physical and mental well-being but also to healthier immune system development. Parents should be encouraged to provide children with regular opportunities to interact with natural environments during their developmental years. In addition, several studies have suggested that early-life exposure to pets may be associated with a lower risk of certain allergic conditions, further supporting the role of environmental exposures in immune system development.

In the most extreme cases of limited exposure to nature, urban day-care yards and similar settings can be enriched with natural forest floor and sod. This is an intervention that has been shown to enhance immunoregulatory pathways in children aged three to five years.

With increased global mobility, families are now able to relocate across countries and continents more easily than ever before. However, a child who is moved early in life may experience a dramatic shift in environmental and ecological exposures compared with those present in their birthplace and ancestral environment. Although migration is often necessary for education, employment, and improved opportunities, sufficient consideration should also be given to a child’s developmental stage and interaction with their surrounding natural environment. Ensuring that children have adequate time to engage with and adapt to local ecosystems may be an important, though often overlooked, aspect of healthy immune system development in an increasingly urbanised and interconnected world.

If we continue to neglect the importance of our connection with nature, future generations may face compromised immune systems, further burdened by heavy air pollution. This could eventually lead to a higher prevalence of IMIDs, increased out-of-pocket healthcare expenditure, and a reduced quality of life. Conserving natural environments should therefore be viewed not only as a means of protecting biodiversity and ecosystems, but also as a potential investment in human health, with the broader goal of safeguarding and promoting a high quality of life for future generations.

Banner image: Children walk through a forest in West Bengal. Reduced exposure to natural environments, changes in dietary patterns, increasing pollution, and sedentary lifestyles have all been implicated in altering immune system development and function. Image by Rangan Datta Wiki via Wikimedia Commons (CC BY-SA 4.0).

Irfan Shakeer is an epidemiologist at Clarivate India. Ayisha Farseena PA is a public health researcher at the state health systems resource centre in Kerala.

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