Harnessing Evolution and Biomimetics to Enhance Planetary Health

Abstract

Planetary health encompasses the understanding that the long-term well-being of humanity is intrinsically linked to the health of global ecological systems. Unfortunately, current practices often overlook this principle, leading to a human-oriented (anthropocentric) worldview that has resulted in heightened greenhouse gas emissions, increased heat stress, lack of access to clean water, and pollution, threatening both the environment and health and survival of Homo sapiens and countless other species. One significant consequence of these environmental changes is the exacerbation of inflammatory and oxidative stressors, which not only contributes to common lifestyle diseases but also accelerates the aging process. We advocate for a shift away from our current anthropocentric frameworks to an approach that focuses on nature's solutions that developed from natural selection over the eons. This approach, which encompasses the field of biomimicry, may provide insights that can help protect against an inflammatory phenotype to mitigate physiological and cellular senescence and provide a buffer against environmental stressors. Gaining insights from how animals have developed ingenious approaches to combat adversity through the evolutionary process of natural selection not only provides solutions for climate change but also confronts the rising burden of lifestyle diseases that accumulate with age.

“Nothing in biology makes sense except in the light of evolution”—Theodosius Dobzhansky

Environmental Factors and Health: Emphasizing Biodiversity in the Anthropocene

Less than 20% of the global burden of adult kidney disease is attributable to genetics.¹ Consequently, environmental factors significantly influence the onset and progression of kidney disease. Human activities cause unprecedented damage to the natural world and the health of the present and future generations. The rate of change is so profound that this geological epoch has been named the Anthropocene.² Over the past 50–60 years (the period of Great Acceleration), humans have altered the planet's climate 170 times faster than the changes that occurred over the previous 7000 years.³ At present, species are disappearing up to 1000 times faster than the historical norm, with a staggering 73% decline in wildlife populations since 1970.⁴ The narrative of life is intricately linked to the planet's evolving geology. Geology and biology are interconnected, shaping one another through the Earth's evolutionary journey. Many researchers believe we are now entering the sixth major mass extinction, and notably, this is the first instance in which geological factors are not contributing to such a dramatic event.

The debate surrounding climate change caused by rising concentration of carbon dioxide in the atmosphere has been resolved—the overwhelming scientific consensus confirms its existence and effect.⁵ Climate change and biodiversity loss represent two of the most significant threats of our time, and they are deeply interconnected. Although we understand the measures needed to reduce greenhouse gas emissions, the actions required to halt the loss of biodiversity are less certain. A frequent misconception is that there is an inherent conflict between human development and environmental conservation, creating a false debate over a choice between prioritizing human needs or those of nature.

We are not only fundamentally dependent on biodiversity for environmental resources, such as clean air and water, fertile soil, and crop pollination, but also for health. Biodiversity plays a crucial role in protecting us from epidemics and pandemics and provides us with a foundation for medical advancements. The conservation of biodiversity is also recognized as being culturally important and psychosocially salutogenic. Given our dependence on natural systems, nephrology should adopt a planetary health approach that highlights the interconnections between kidney disease, dietary habits, and animal and environmental health. In this context, we explore the significance of biodiversity and planetary health in relation to kidney disease.

Understanding Kidney Vulnerability during the Anthropocene

The kidneys safeguard the body against water and electrolyte imbalances, but they also eliminate toxins and protect us from environmental stressors. As essential filters for environmental contaminants, the kidneys are particularly vulnerable in polluted, arid, and hot environments. While climate change and air pollution represent external threats, compromised kidney function creates an internal environmental risk that causes a gradual buildup of both endogenous and exogenous toxins.^6,7 Currently, kidney disease affects 10% of the global population, and the incidence of CKD has increased by 36% between 2010 and 2017.⁸ By 2040, CKD is projected to become the fifth leading cause of years of life lost. Given our expertise in understanding how internal waste products affect biological systems,⁹ nephrologists are particularly well positioned to investigate the effects of environmental pollution on human health.

Over the course of evolution, the mammalian kidney has evolved in response to a series of catastrophic planetary changes, including climate shifts and mass extinctions. Its unique features (such as the high-pressure, high-flow glomeruli; mitochondria-rich tubules; and the hyperosmotic, hypoxic medulla) make the kidney particularly vulnerable to circulatory and toxic injuries. The interplay between these anatomical constraints and environmental threats promote trade-offs and mismatches that ultimately can lead to nephron loss.¹⁰ As natural selection is primarily driven by reproductive fitness rather than longevity, this explains the exponential rise in kidney disease as individuals age. This phenomenon is attributed to antagonistic pleiotropy, where certain genes beneficial for reproduction may have detrimental effects on health later in life.

CKD: The “Black Lungs” of Climate Change

Western diets rich in ultra-processed foods and sugar are well-recognized drivers of metabolic diseases, CKD, aging, and mental health issues,^11–15 but they also negatively affect the environment.¹⁶ While ultra-processed foods confer metabolic risk, food and water may also contain toxins, such as xenobiotics, pharmaceuticals, endocrine-disrupting compounds, pesticides, phosphate additives,¹⁷ and micro- and nanoplastics.¹⁸ Global water shortages are looming, and the United Nations recently reported that at least 50% of the world's population experience water shortages for at least 1 month each year.¹⁹ Lack of clean water and ground water contamination are risk factors of CKD.²⁰

Global temperature has increased by 1.11°C since the late 19th century and has precipitated a surge in heat waves. June 2024 marked the 12th consecutive month that the average temperature on land and in the oceans was at least 1.5°C above the average calculated from the months between 1850 and 1900. The underlying causation is unequivocal: the rising concentration of atmospheric carbon dioxide, of which every third molecule is anthropogenic in origin.²¹ The 2022 summer heatwave in Europe resulted in nearly 62,000 fatalities and highlights the deadly consequences of extreme weather events.²² Patients with CKD, especially those on dialysis, are especially at risk,²³ and care providers must take action to protect this vulnerable population against the consequences of climate change.²⁴

Heat stress can disrupt sodium and potassium balance, cause AKI, and is linked to a higher frequency of hospital admissions for kidney-related conditions.²⁵ In warmer regions, such as Central America, Mexico, India, and Sri Lanka, there have been alarming outbreaks of an enigmatic CKD of unknown etiology.²⁶ This condition predominantly affects male agricultural laborers who endure strenuous working conditions in oppressive heat. They typically labor under temperatures exceeding 29°C for 6–8 hours a day, 6 days a week, throughout the 5- to 6-month harvest season. Post hoc analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial has shown that patients with CKD living in the hottest countries experienced an additional 3.7 ml per 1.73 m² loss of eGFR each year compared with those living in temperate climates.²⁷ Inflammatory proteins triggered by heat stress may contribute to kidney damage, suggesting a potential pathway for prevention.²⁸ Overall, the current scenario indicates that kidney disease is becoming the “black lung” of climate change and could function as a critical indicator of the effect of the environment (Figure 1).

Figure 1.

Kidneys are particularly vulnerable to a rapidly changing environment. It can be hypothesized that the rising global incidence of kidney disease reflects the effects of climate change. As such, kidney disease may be considered the “black lungs” of climate change. Scientific research has shown that various factors—including the consumption of ultra-processed foods, insufficient access to clean water, viral pandemics, exposure to toxins, heat stress, air pollution, psychosocial stress, and urbanization—contribute to the growing global burden of kidney disease.

Urbanization, Air Quality, and Kidney Health: A Complex Relationship

A growing body of research indicates that polluted air promotes inflammation.²⁹ In 2021, particulate matter (PM_2.5) emerged as the leading contributor to the global disease burden.³⁰ According to the World Health Organization, polluted air is responsible for over 7 million premature deaths each year³¹ and may accelerate aging.³² PM_2.5 is associated with a higher risk of CKD and/or signs of kidney injury, especially in India and China,³³ but also in areas considered to have good air quality, such as Sweden.³⁴ The relationship between long-term ambient air pollution and CKD has been noted especially in the United States, where the combined exposure to air pollution and heat is associated with greater morbidity and mortality in patients receiving dialysis.³⁵ Certain risk factors may exacerbate risk of worsening kidney function in the setting of poor air quality, including abdominal obesity,³⁶ a history of kidney transplantation,³⁷ or kidney donation.³⁸ Although the exact mechanisms by which air pollution incites kidney disease remain unclear, it is hypothesized that inflammation either mediated by a disturbed gut ecosystem³⁹ or mediated by a disruption of the nuclear factor erythroid two–related factor 2 (Nrf2) pathway by PM_2.5 plays a role.^40,41 Nrf2, an important stress regulator that serves as a hub for renal transcriptional networks,⁴² protects against kidney disease progression,⁴³ mitochondrial dysfunction, and inflammation.⁴⁴ Nrf2 deficiency leads to impaired mitochondrial fatty acid oxidation, respiration, and ATP production.⁴⁵ This raises the possibility that nutritional Nrf2 activators offer protection for vulnerable populations in air-polluted regions.⁴⁶ Encouraging a shift toward more plant-based diets could be an effective strategy for mitigating ambient air pollution and reducing the related health and economic effects.⁴⁷

The presence of greenery in outdoor and residential facilities reduces the risk of cardiovascular disease,⁴⁸ improves the well-being of critically ill patients,⁴⁹ reduces health care costs,⁵⁰ and protects against new-onset CKD.⁵¹ The walkability of cities is associated with improved physical activity of patients receiving dialysis.⁵² Urbanization is associated with higher levels of PM_2.5 and NO₂, more CKD,⁵³ and inflammation.⁵⁴ Because socioeconomic position influences the risk of CKD,⁵⁵ the geophysical environment within specific urban post codes seems to play a far greater role than previously expected.

Biomimetics: Nature's Ingenious Solutions

Nature's biodiversity may be endangered by the effect of climate change and pollution, but it may also provide solutions. The field of evolutionary medicine has made significant strides over the past 30 years by linking disease vulnerability to evolutionary adaptive responses. This approach not only enhances our understanding of how diseases progress but also sheds light on the underlying reasons for their occurrence.^10,56 Natural products and their structural analogs have historically made a major contribution to pharmacotherapy.⁵⁷ Many species have evolved ingenious solutions through natural selection that could be adapted to combat the anthropogenic stressors. Biomimicry is the scientific discipline that identifies these biological systems in nature and melds them into an interdisciplinary framework to find solutions to disease and/or human problems. In essence, biomimicry provides a novel approach to achieving health and sustainability^58,59 and shifts the focus from an anthropocentric perspective toward a more naturogenic worldview that recognizes humanity as one integral element of a larger, indivisible natural ecosystem.⁶⁰

Examples of biomimetic application in nephrology include: (1) the development of captopril, which was derived from a bradykinin-potentiating peptide found in the venom of the Brazilian viper Bothrops jararaca⁶¹; (2) sodium-glucose cotransporter-2 (SGLT2) inhibitors—an established treatment strategy of progressive CKD.⁶² SGLT2 inhibitors originated from phlorizin, an element identified by chemists in the bark of apple trees during the 1830s that was later shown to cause a rapid increase of sugar in urine.^63,64 By blocking the uptake of glucose into the kidney, it triggered a switch to fat oxidation similar to estivating animals that allowed them to survive periods of food shortage or drought⁶⁵; and (3) the discovery that Gila monster venom could prolong the biological effect of glucagon-like peptide-1 that led to the development of a new class of drug that now benefit humans. These nature-based drugs treat not only type 2 diabetes but are also used to treat obesity⁶⁶; slow progression of CKD⁶⁷; improve heart failure⁶⁸; and possibly decrease addictive behavior, such as smoking⁶⁹ and alcoholism.⁷⁰

Natural selection has developed mechanisms that shield animals from the effect of lifestyle diseases, pedagogical for enhancing health and well-being in human populations.¹¹ Hibernating bears are protected from osteoporosis, muscle wasting, type 2 diabetes,⁷¹ immobility-associated thrombosis,⁷² and arteriosclerosis.⁷³ Numerous other protective traits have been documented across a variety of species (Figure 2). The natural world also presents a range of ingenious solutions for protecting kidney function. For instance, deep-diving seals have developed mechanisms that safeguard them against AKI,⁷⁴ while bears exhibit protective adaptations that allow them to endure months of anuria during hibernation.⁷⁵

Figure 2.

Nature offers a wealth of ingenious solutions that may enhance health and address climate challenges. Natural products and their structural analogs have historically played a significant role in pharmacotherapy, contributing not only to the treatment of cancer and infectious diseases but also to the advancement of treatment of CKD, as indicated in green. Derived from the venom of the Gila monster, GLP-1 receptor agonists are used to manage diabetes and obesity.¹²⁹ Found in the venom of the Brazilian viper, bradykinin-potentiating peptides form the basis of therapeutic strategies for CKD.⁶¹ Originating from phlorizin, discovered in the bark of apple trees during the 1830s, SGLT2 inhibitors are now key in CKD management.^63,64 Cyclosporin¹³⁰ and rapamycin,¹³¹ sourced from fungus and bacterium, are critical for success in transplantation. Found in the death cap mushroom, the orellanine toxin is selectively harmful to kidney cells but has been harnessed in treating metastatic kidney cancer, despite the risk of kidney function loss.¹³² Furthermore, nature provides insights into understanding disease mechanisms and developing innovative treatment strategies, as indicated in blue. Hibernating bears are metabolic marvels that offer insights into protection against osteoporosis, muscle wasting, type 2 diabetes, thromboembolism, obesity, and arteriosclerosis.⁷¹ With the highest recorded BP in the animal kingdom (300/180 mm Hg), giraffes exhibit no damage to their kidneys, heart, or brain, thanks to a protective genetic mutation that has been successfully transferred to mice.¹³³ Bats have become models for healthy aging, showcasing remarkable defenses against chronic inflammation and viral infections.¹³⁴ Burmese Pythons undergo significant organ growth after feeding, attributed to an enriched NRF2-mediated oxidative stress response.¹³⁵ Tree shrews are an unassuming species that thrive on nectar from brewery-scented palm trees; they demonstrate intriguing resilience to high alcohol content.¹³⁶ Sharks are renowned for their ability to self-heal and regenerate skin.¹³⁷ The sluggish Greenland shark (Somniosus microcephalus) has an average lifespan of at least 250 years but can potentially reach a lifespan over 500 years. It was recently reported that genes duplicated in this shark form a functionally connected network enriched for DNA repair function.¹³⁸ Adapted to deep-sea diving, seals possess mechanisms to protect their kidneys from oxygen deprivation.¹³⁹ Despite the risks of fatty liver and blood glucose spikes from their high-sugar diet, hummingbirds demonstrate remarkable metabolic resilience, leading to insights into diabetes management.¹⁴⁰ Komodo dragons exhibit strong immunity in bacterium-laden environments, and a synthetic molecule derived from their blood is being explored as a potential antibiotic.¹⁴¹ Sleeping only approximately 2 hours a day, elephants also display resilience to cancer, possessing an incredible 40 copies of the p⁵³ gene, providing them with superior cancer protection.¹⁴² Naked mole rats are unique for their insensitivity to pain, exceptional cancer resistance, and maintenance of youthful vascular health.¹⁴³ Hippos secrete a reddish fluid once mistaken for blood—this natural UV-blocking compound protects their skin from the harsh African sun.¹⁴⁴ Adapted to desert environments, camels endure extreme temperature fluctuations and demonstrate efficient water conservation. Their milk is rich in vitamin C, lactobacilli, and immunoglobulins, offering protective benefits by activating the Nrf2 pathway.¹⁴⁵ Nephrologists can also glean lessons from animal species that exhibit susceptibility to disease, highlighted in red. The significantly higher risk of CKD in nondomesticated felids offers insights into dietary risk factors, particularly the consumption of red meat, enhancing our understanding of CKD susceptibility and prevention strategies.⁸⁰ ACE, angiotensin-converting enzyme; GLP-1, glucagon-like peptide-1; Nrf2, nuclear factor erythroid two–related factor 2; SGLT2, sodium-glucose cotransporter-2.

Excluding animals from their natural habitat, whether for a short period (such as in captivity) or a longer duration (as seen in domestication), poses significant health risks. Bears in captivity lose their protective phenotype and are at higher risk of disease and premature aging.⁷⁶ Kidney disease and vascular calcification are prevalent among felids in captivity,⁷⁷ while the diversity of the gut microbiome exhibits stepwise decrease in primates living in wild, semicaptive, and captive conditions.⁷⁸ These health risks reflect the effects of modernization and urbanization in humans and likely share a common foundation. Recognizing this shared ground may bridge the gap between human medicine and veterinary medicine. After all, Homo sapiens is merely a small branch on the vast phylogenetic tree of the animal kingdom.

Studies of the natural world have also identified protective mechanisms that have unintended consequences in modern society. For example, metabolism of fructose either from diet or generated endogenously from carbohydrates likely may be associated with better survival by stimulating foraging and accumulation of fat to assist an animal at risk of food or water shortage.⁷⁹ However, in Western society, excessive fructose intake from added sugars or from production from high glycemic carbohydrates has likely played a role in the epidemic of obesity and metabolic-associated diseases.

How Nature Shields Animals from Environmental Changes

Understanding how animals survive extreme environments⁸⁰ or rapidly adapt to changing environments is of significant interest.⁸¹ Some species are rapidly evolving to survive in response to global warming⁸² and have undergone adaptive physiological changes to climate change.⁸³ One of the most compelling examples of how animal species have evolved powerful defense mechanisms against environmental threats is seen in bats, which have evolved potent host defense systems that block inflammation and protect energy metabolism.^84,85

One common characteristic strategy associated with survival is the presence of advanced defense mechanisms to protect the organism from oxidative stress, inflammation, and mitochondrial dysfunction—survival requires a robust maintenance of cellular energy levels. Oxidative stress, often exacerbated by environmental disruptions, is linked to a range of diseases and drives aging.⁸⁶ Global warming, pollution, and lack of clean water drives an inflammatory phenotype characterized by metabolic dysregulation, oxidative stress, cellular senescence, DNA damage, tissue hypoxia, mitochondrial dysfunction, Nrf2 depletion, and impaired autophagy.⁸² Heat stress induces apoptosis and/or inflammatory signaling across a range of tissues,^80–83 coincident with premature cellular senescence.⁸² As heat stress⁸⁷ and air pollution⁸⁸ cause DNA damage, environmental cues thus drive premature aging. The effects of climate change on mental health and psychosocial stress may indirectly contribute to inflammation through endogenous psychosocial stress–related mechanisms and disease sequelae.^89,90 In summary, environmental changes seem to trigger the same inflammatory phenotype that promotes lifestyle diseases. This phenomenon exacerbates the widening gap between human health span and lifespan in the Anthropocene epoch.

The Role of the Mitochondria and the Mitochondrial Antioxidant Nrf2

The intricate relationship between mitochondrial biogenesis and climate change underscores the complexity of biological responses to environmental shifts and involves the coordinated regulation of both nuclear and mitochondrial genomes in response to exposome changes.⁹¹ Exposome refers to the totality of environmental exposures that an individual encounters throughout their life. Notably, this includes transgenerational effects that can be transmitted along both paternal and maternal lines. While matrilineal inheritance encompasses mitochondrial inheritance as part of an egg, paternal effects are also transmitted in the form of mitochondrial RNAs,⁹² enabling rapid and dynamic epigenetic regulation of gene expression in response to environmental change, in particular diet. Similarly, chloroplasts responsible for energy production in plants are also susceptible. Tropical forests are now approaching a critical temperature threshold that could affect photosynthesis.⁹³

Essential to these processes are the activity of several genes that are considered key regulators of mitochondrial biogenesis, including (1) peroxisome proliferator–activated receptor gamma coactivator 1α that coordinates the activation of the transcription factors involved in mitochondrial biogenesis. When a protein that inhibits proliferator–activated receptor gamma coactivator 1α is blocked, mitochondrial function improves, resulting in enhanced protection for organs. This innovative strategy is exemplified in the natural world by the Atlantic bluefin tuna, which benefits from a strong physiological foundation that enables it to thrive in the ocean's fast lane⁹⁴; (2) mitochondrial transcription factor A: a key activator of mitochondrial DNA transcription and replication; and (3) nuclear respiratory factors 1 and 2 (Nrf1 and Nrf2): transcription factors that regulate the expression of nuclear genes encoding mitochondrial proteins and, in the case of Nrf2, regulation of most cytoprotective responses.

Nrf2 represents a crucial pathway used by many species during oxidative stress.⁴⁵ Nrf2 evolved during the Great Oxygenation Event that occurred approximately 2.4 billion years ago.⁹⁵ Loss of Nrf2 is linked with increased cellular aging.⁴⁴ Various animal species have developed mechanisms to maintain elevated levels of Nrf2 as a survival advantage against environmental stress.⁴⁴ Long-lived species, such as rougheye rockfish, naked mole rats, and bats, have protective mechanisms to combat inflammation, reduce mitochondrial dysfunction and DNA stress, and mitigate oxidative stress.⁹⁶ In addition, some species use the activation of the Nrf2/heme oxygenase-1 pathway as defense against heat stress.⁸² Nrf2 plays a role also in resistance against other forms of environmental stressors,⁴⁶ such as microplastics⁹⁷ and nickel exposure.⁹⁸ Whereas mussels use Nrf2 to protect from toxins, such as benzo(a)pyrene,⁹⁹ it may also be used as a defense against air pollutant exposure.¹⁰⁰ Thus, treatment opportunities that include plant-based Nrf2 activators,¹⁰¹ such as sulforaphane⁴⁶ and fucoidan,¹⁰² may offer protection against exposome stress. Because environmental stress triggers the same inflammatory and oxidative processes that accelerate aging,¹⁰³ implementing such treatment strategies may result in a win–win scenario—what benefits the planet enhances our health.

Shifting Toward Sustainability: Reducing Red Meat Intake for Health and the Planet

Results from a meta-analysis indicate that total and mixed red meat consumption, but not unprocessed red meat, significantly increased C-reactive protein concentrations.¹⁰⁴ Besides a proinflammatory effect, red meat accelerates the biological aging processes¹⁰⁵ and increases greenhouse gas emissions through industrialized farming.¹⁰⁶ The connection between red meat consumption and cancer was recently strengthened by a study of 110,000 animals from 191 species.¹⁰⁷ Although many factors may contribute to the linkage between red meat and CKD, recent research highlights the role of trimethylamine oxide (TMAO) in increasing susceptibility to health issues. Because free-ranging bears seem to activate a metabolic switch that redirects to the production of betaine instead of TMAO, characterizing and understanding this adaptive mechanism could provide insights into new treatment options for CKD.¹⁰⁸ Betaine plays a significant role in methylation processes in the body, particularly in the conversion of homocysteine to methionine, which is important for various metabolic functions. Higher serial measures of plasma TMAO were associated with higher risk of incident CKD and greater annualized kidney function decline.¹⁰⁹ Notably, the association with eGFR decline was equivalent or greater than seen for established CKD risk factors, including diabetes, systolic BP, older age, and race. Thus, patients with CKD should restrict their intake of red meat (especially ultra-processed meats and red meat from farmed ruminant species) both for health and environmental reasons.¹¹⁰

More than half of food-related greenhouse gas emissions originate from animal products. Contrastingly, plant-based diets produce 75% fewer climate-heating emissions, reduce water pollution, and require less land compared with domestic ruminant meat–rich diets.¹¹¹ Thus, a shift toward plant-based nutrients coupled with red meat restriction may not only reduce greenhouse gas emission and the risk of burden of lifestyle diseases but also prevent adverse health effects by exposome stressors and support environmental stability.^47,112,113

The Loss of Biodiversity Is Mirrored by a Decline in the Diversity of Gut Microbiota

It is crucial to recognize that our microbial exposome has been affected adversely during the Anthropocene.¹¹⁴ Concurrently, many rural areas are experiencing a decline in soil biodiversity. The increased use of agrochemicals, reduced plant diversity, and intensive soil management practices negatively affect crop biodiversity.¹¹⁵ These developments coincide with an increase in lifestyle diseases related to the human intestinal microbiome. The microbiome of hunter–gatherer and subsistence farming communities is characterized by high microbial biodiversity and ancient microbial lineages that are increasingly rare in modern industrialized societies.¹¹⁶ By contrast, Western diet and lifestyle have led to selection of a more restricted microbiome¹¹⁷ that increases the risk of lifestyle-associated diseases, including CKD¹¹⁸ (Figure 3). The gut microbiome plays a crucial role in inducing Nrf2 in the liver,¹¹⁹ highlighting the importance of gut bacterial composition for antioxidant and anti-inflammatory responses. A dramatically decreased consumption of dietary fiber is increasingly recognized as a major driver of the microbiome shift, in which generations have progressively lost their capability to metabolize complex carbohydrates. The decline in the consumption of fermented food products has further adversely affected our gut microbiome.¹²⁰ Microbiota reprogramming thus needs to involve strategies that incorporate dietary microbiota-accessible carbohydrates and taxa not present in the Western gut.¹²¹ Just as the human microbiome is essential for our health, the global microbiome plays a pivotal role in the functioning of Earth's planetary systems. The widespread and vital role of microbes presents unique opportunities for us to collaboratively enhance progress toward the United Nations's various sustainability goals.¹²²

Figure 3.

Gut microbiome at the interface between exposome and diseasome. Environmental stressors including an unbalanced diet, sedentary lifestyle, air pollution, and heat stress may mediate lifestyle diseases partly by disturbing the gut microbiome. A disrupted gut microbiome, reflected by a decreased a-diversity, a shift from Bacteroides to Firmicutes predominance, and suppressed carbohydrate fermentation, may compromise the gut epithelial barrier and gut epithelial mitochondrial bioenergetics and disturb bidirectional communication with the host, the latter involving immune, endocrine, humoral, and neural signals.^146,147 Pathophysiological pathways are complex, but mounting evidence identifies oxidative stress and inflammation as central drivers.¹⁴⁸ IBD, inflammatory bowel disease.

Environmental stressors, such as heat, may further modify gut flora composition¹²³; for example, a mere 2°C–3°C temperature rise led to a reduction in gut bacterial diversity in lizards.¹²⁴ Moreover, exposure to air pollutants have the potential to alter the composition and diversity of gut microbiota.¹²⁵ Targeting the gut microbiome through hydration, better air quality, balanced diets, and nutraceuticals can help mitigate the potentially harmful effects of heat stress.¹²⁶ Indeed, strategies to address gut dysbiosis by focusing on the foodome and other exposome stressors may help identify ways to prevent or treat human diseases.¹²⁷ Of approximately 2000 plants that are known dietary fiber sources, only a few are being used. These offer the potential to effect real-time modulation of the epigenetic landscape of aging by bioactive compounds in food, such as betaine in beet roots—the “pink pressure.”¹²⁸

Toward a One Health Approach: Nephrology and the Need for Biodiversity Conservation

Nephrologists need to increase their understanding of the effect of adverse exposome stressors on global kidney health. In the coming decades, we will witness the eventual predominance of climate-related and toxin-associated kidney diseases. Recognizing that exposome biodiversity in natural ecosystems significantly influences our health, its bioconservation is crucial for the well-being of kidneys in future generations. By preserving and promoting biodiversity, we can ensure that ecosystems continue to deliver essential services while safeguarding our physical and mental health. Embracing a profound reverence for nature and integrating our own individual intellectual capabilities with artificial intelligence and biological intelligence¹⁴⁹ can serve as a crucial lifeline. Intersectoral research initiatives that connect the dots are essential for bridging the gaps between these disparate research domains, ultimately advancing the World Health Organization's One Health agenda.

Supplementary Material

jasn-36-311-s001.pdf ^{(1.3MB, pdf)}

Disclosures

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/E971.

Funding

None.

Author Contributions

Conceptualization: Pieter Evenepoel, Richard J. Johnson, Peter Kotanko, Paul G. Shiels, Peter Stenvinkel.

Writing – original draft: Peter Stenvinkel.

Writing – review & editing: Pieter Evenepoel, Richard J. Johnson, Peter Kotanko, Paul G. Shiels.