Abstract
Stress is universal, and its toll on mental and physical health is undeniable. Health care systems, however, remain largely reactive—treating patients only after chronic stress has fueled conditions such as depression, heart disease, or gastrointestinal disorders. The critical question is not how to manage stress once it becomes pathological, but how to prevent it from taking root in the first place—and whether the body can be trained to adapt more effectively to life’s inevitable challenges.
Resilience has many definitions, but in the context of stress, it generally refers to our ability to cope after a threat or stressful events. Stress resilience involves the acceptance of change, tolerance of negative affect, tenacity, and the ability to recover after stressful events. 1 A growing body of research suggests that stress resilience is not a fixed trait that a person either has or doesn’t; it’s a trainable phenotype that we can build, measure, and maintain. This resilience emerges from the dynamic interplay between flexible emotional regulation and the brain–gut–microbiome (BGM) axis.
A Primer on Good Stress and Bad Stress
In Super Agers, Eric Topol delineates the difference between lifespan and health span. Lifespan is the number of years that a person at a given age is expected to live, while health-adjusted life expectancy (HALE) is the average number of years spent in good health. 2 One way to think of it: it’s the difference between spending the last few decades of your life managing chronic diseases, or maintaining a good quality of life and mobility well into old age. Several factors impact a good HALE, which Topol describes as lifestyle+: a well-balanced diet, regular aerobic and muscle-strengthening physical activity, good-quality sleep, minimal exposure to environmental toxins, and companionship—factors associated with a marked improvement in healthy aging. 2
Longevity is not reactive—it is a prevention-first approach grounded in specific behaviors and choices, such as eating fewer ultra-processed foods (UPFs) and practicing good sleep hygiene. Learning how to manage stress is an important part of this picture because stress impacts Topol’s longevity+ factors; over time, heightened cortisol due to a person’s stress response may prompt them to eat more sugary foods, prevent them from getting restful sleep, or respond as well to exercise. There is a difference between “good stress” and “bad stress”—the former is adaptive and helps build resilience, while the latter has negative consequences for our biology.
In healthy conditions, stress is not always bad. The stress system evolved to help us respond to our environment and enhance survival; it is both highly reactive and capable of long-term adaptation.³ The acute stress response mobilizes energy and sharpens cognition, and the body returns to baseline via negative feedback mechanisms in the nervous system. This is “good stress”—the type that builds neurobiological preparedness for future stressors and a stronger ability to cope.
In contrast, “bad stress” is chronic, uncontrollable, and maladaptive, to the point that it interferes with the body’s ability to return to homeostasis—another way of saying that stress fails to shut off. The body moves into allostasis, a new normal that wears down the cardiovascular, immune, metabolic, and neural systems. That load raises the risks of mood and anxiety disorders, diabetes, cardiovascular disease, and other conditions. The biology of resilience sits at this junction: the capacity to mount a vigorous stress response when needed and then return to baseline efficiently, without burning out. 3 Recent systems biology reviews underscore this as a dynamic, trainable process—rooted in neuroplastic adaptations across brain–body networks—that buffers against allostatic overload, inviting targeted interventions to rewire vulnerability into strength.
The brain is not the only player in the body’s stress response. The gut—with its approximately 40 trillion microorganisms, gut-associated lymphoid tissue and role in immunity, and its bidirectional vagal highway to the brain—impacts how that stress unfolds. Some BGM links are firmly established, such as how the gut and brain communicate via the vagus nerve, immune signals, endocrine pathways, and microbial metabolites. Certain gut bacteria have been found to synthesize or influence neuroactive compounds (GABA, dopamine, acetylcholine, serotonin precursors), contributing to tone in neural circuits tied to mood and arousal. 4 And treatments targeting the vagus nerve have been shown to increase vagal tone (the activity of the vagus nerve) and inhibit cytokine production, both of which are important mechanisms of resiliency. 5 Vagal tone is correlated with the capacity to regulate the stress response, and it is an essential part of the brain–gut axis.
Other BGM signals are newer but compelling. A 2024 study surveyed 116 people about their resiliency and separated them into high-resiliency (HR) and low-resiliency (LR) groups. 1 Participants underwent MRI imaging and gave stool samples. People in the HR group were less anxious and depressed, less prone to judge, and had activity in the brain regions associated with emotional regulation and cognition compared with the LR group. The HR group also had different microbiome activity than the LR group; the former had metabolites and gene activity associated with low inflammation and a strong gut barrier.
Early clinical cues point in the same direction. An exploratory study investigated the microbiome of patients with PTSD and trauma, revealing that PTSD patients had fewer bacteria strains important for immune regulation, which could have contributed to immune system dysregulation and the development of PTSD symptoms. 6 We are far from proving causality in humans, but early evidence suggests that resilient minds and well-regulated guts are connected.
Building on these brain–gut insights, training stress resilience involves targeted interventions that leverage this axis, from psychological tools to lifestyle tweaks.
A Path Toward Stress Resilience
So, how do we train people to have healthier responses to stress and promote stress resilience? Decades of research show that there is no single “gold standard” coping strategy that always works. Instead, what matters is training the ability to remain sensitive to the situational context, utilize a diverse repertoire of regulatory strategies, and monitor feedback to maintain or adjust regulation as needed. 7 Taken further, deliberately building stress resilience must happen in layers: before, during, and after exposure to the stressor.
Pre-exposure inoculation with skills
Similar to the way a vaccine inoculates the body against disease, stress inoculation training (SIT) helps inoculate individuals to future potentially traumatizing stressors by teaching them to manage them more effectively. 8 With SIT, patients conceptualize the stressor, acquire and rehearse coping skills, and then apply them in regular life. One example of SIT is virtual reality therapy with physiological monitoring. In VR, clinicians can precisely titrate the “dose” (intensity, duration, and frequency of the stressor) and capture objective markers, such as heart rate/heart rate variability (HRV) dynamics, breathing, and even sweat responses, while the patient practices emotional regulation strategies under safe, controlled pressure. VR-assisted exposure with physiological feedback has been shown to be particularly useful in clinical settings and contributes to low dropout rates in PTSD treatment. 9
HRV biofeedback
Evidence suggests that HRV biofeedback yields large reductions in perceived stress and anxiety. HRV is a measure of cardiac vagal tone, and high resting HRV has been shown to predict self-regulatory strength and reduced negative emotions during acute stress. 10 Breathing training, yoga, and mindfulness meditation exercises may enhance a patient’s ability to regulate their emotions during high-stress periods. In addition, HRV training pairs well with CBT and other therapy modalities and is increasingly accessible via consumer wearables—people can easily monitor their heart rate with an Apple Watch or a similar wearable heart rate monitor and practice breathing exercises with live feedback during high-stress periods.
Diet
What we eat directly impacts our microbiome, and we know that the microbiome talks to the brain. A small randomized trial of a psychobiotic diet (higher in prebiotic fibers and fermented foods) reduced perceived stress and shifted microbial metabolites in healthy adults. 11 The effects were modest and group differences were limited, so caution is warranted, but the risk is low and dovetails with Topol’s longevity guidance: minimize UPFs; emphasize vegetables, legumes, whole grains, nuts, seeds, olive oil, and omega-3-rich fish; and maintain consistent sleep–wake cycles to support the gut’s circadian rhythm. Diet is not the only path toward stress resilience—it is one piece of a series of foundational levers (sleep, physical activity, and managing one’s stress response).
Nature-informed curricula
Emerging pilots in educational settings, such as forest-bathing integrated into college courses, have shown promise in slashing perceived stress while bolstering resilience scores—offering a simple, group-based layer that blends ecological immersion with stress education. 12 These scalable models, especially when augmented with digital tools such as VR nature exposure, point to hybrid approaches ripe for broader testing in high-stress populations.
These elements work together to help promote long-term resilience. While new therapeutics, such as GLP-1s and microbiome engineering, are exciting, it will be “hard for any new drug or intervention to match the overwhelming consequences of a well-guided healthy lifestyle,” but that doesn’t mean these emerging therapies aren’t worth pursuing. 2
Evidence suggests that we are facing a second pandemic of mood and anxiety disorders, but scientific knowledge can be deployed at multiple levels to help promote a more resilient society
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Prioritize mental health as a target at the national and global levels, and adopt the notion that mental health care is a human right. At the state, municipal, and local levels, guide public policy to create an integrated infrastructure to address mental health issues within school systems, workplaces, and the broader community. Increase awareness about the mental health crisis among mental health care workers, provide mental health resources, and incorporate evidence-based approaches into treatment programs. Provide scientifically based guidelines to shape lifestyle interventions to reduce stress and build resilience at the individual level, including behavioral interventions, diet, nutrition, and digital hygiene.
Resilience is not the absence of stress—it is the trained capacity to rise after you fall.
Beneath the mind’s storm, the gut quietly roots: each breath a filament along the vagus, and each fiber a signal to calmer circuits. We do not outrun the gale—we grow through it. A prevention-first world demands that we stop waiting for breakdown and start building unbreakable adaptation—one rooted meal, one measured pulse, and one quiet dawn at a time.
Brenda K. Wiederhold
Editor-in-Chief