Helen Frankenthaler Foundation

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The Effects of Psychobiotics and Adaptogens on the Human Stress and Anxiety Response: A Systematic Review

Abstract

In recent years, growing interest has emerged in the use of psychobiotics and adaptogens for regulating stress and anxiety. However, it is essential to assess their effectiveness as treatment alternatives, particularly given the limitations of conventional approaches, such as adverse effects of pharmacological therapies and the limited remission rates associated with psychotherapy alone. This systematic review primarily aims to assess how effective psychobiotics and adaptogens are in alleviating stress- and anxiety-related psychophysiological symptoms. A secondary aim is to identify specific bacterial strains and herbal compounds most consistently linked to beneficial outcomes. An extensive search was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar using the terms ((adaptogens) OR (psychobiotics)) AND (stress), resulting in 23 selected articles. The findings suggest that both psychobiotics and adaptogens show promise in reducing stress- and anxiety-related symptoms. Bifidobacterium longum and Lactobacillus rhamnosus were frequently associated with improved gut–brain axis regulation, while Withania somnifera and Rhodiola rosea demonstrated physiological benefits through cortisol reduction and stress adaptation. Although results are encouraging, further research is needed to confirm long-term efficacy and clarify the specific mechanisms and compounds responsible for these effects.

Introduction

Stress is a multifaceted physiological and psychological response influenced by environmental, chemical, and psychological factors. Acute stress specifically involves an immediate psychophysiological response to a perceived or real threat, challenge, or significant event, which is typically short-lived and subsides once the stressor is removed. It is driven by the activation of the hypothalamic–pituitary–adrenal (HPA) axis, leading to the release of stress hormones such as cortisol, epinephrine, and norepinephrine, which facilitate the ‘fight or flight’ reaction. Furthermore, one possible response to stress, particularly in acute situations, is anxiety. Unlike acute stress, anxiety is characterized by its anticipatory nature, arising in response to perceived future threats and manifesting feelings of apprehension and worry. Anxiety symptoms are key indicators of stress-related dysregulation.

Life events significantly contribute to stress reactions, with chronic illness, divorce, house moving, caregiving, and exam periods being recognized as major stressors. While an efficient stress response enables effective coping, chronic overstimulation—known as allostatic load—can disrupt HPA axis function, leading to physical and mental health issues such as cardiovascular disease, post-traumatic stress disorder, and depression. In Spain, anxiety-related mental health issues have increased by 105% from 2016 to 2021, making anxiety disorders the most prevalent mental health concern, affecting 126.9 per 1000 residents and leading to a higher consumption of psychotropic medications, particularly anxiolytics, which account for 9.1% of total medication use. The widespread prescription and consumption of these medications raise concerns, as pharmacological treatments for emotional disorders are associated with several adverse side effects. Moreover, a substantial proportion of individuals receiving psychotherapy alone do not achieve full remission. Given the undeniable role of stress as a mediator in mental and physical health, exploring diverse strategies to mitigate its effects could yield substantial societal benefits.

Emerging research highlights the role of gut microbiota in regulating emotions, cognition, and behavior. Microbiota are understood as the multitude of microorganisms, such as bacteria, archaea, yeasts, etc., that the human gut hosts. The gut–brain axis enables bidirectional signaling via endocrine, neural, and immune pathways. It is of paramount interest to know that microbiota affects the HPA axis, and consequently, the release of cortisol, involved in the stress response. Dysbiosis, or alterations in gut microbiome composition, has been linked to emotional disorders, such as anxiety-related disorders. Modulating microbiota presents potential benefits for mental health, particularly through substances like psychobiotics and adaptogens.

Background on Psychobiotics

The term “psychobiotics” was defined as “live microbes that have a positive mental health benefit”. Probiotics and prebiotics have shown promising potential as psychobiotic agents with increasing evidence on how they affect the central nervous system. Evidence shows that psychobiotics exert significant benefits on stress, mood, anxiety, and cognitive processes. Specifically, psychobiotics have been shown to reduce anxiety-like and depression-like symptoms while normalizing key physiological markers such as cortisol, corticosterone, noradrenaline, brain-derived neurotrophic factor, and immune function.

Notably, certain bacterial strains, such as Bif. longum and L. helveticus, have been extensively studied for their potential role in modulating emotional behavior and stress responses. When administered together, these strains may promote beneficial changes in psychosocial factors and psychiatric symptoms, supporting their classification as psychobiotics. However, while some studies report positive outcomes, others have found limited or no effects. For instance, Romijn et al. found no significant effects on depression, while Messaoudi et al. reported no changes in perceived stress. In contrast, Gruenwald et al. observed improvements in general well-being, and Rao et al. noted improvements in anxiety. Furthermore, Messaoudi et al. observed a reduction in urinary cortisol levels over time; however, this combination failed to enhance the cortisol awakening response (CAR) or salivary cortisol levels.

Background on Adaptogens

Adaptogens are pharmacologically active compounds or extracts derived from various plant classes, recognized for their ability to enhance the body’s adaptation to stress and maintain metabolic homeostasis. Their consumption has been linked to improvements in both mental and physical performance and has demonstrated anti-fatigue, antidepressant, anxiolytic, stress-reducing, and healthy-aging properties. Their primary mechanism of action involves regulating the HPA axis and modulating key stress mediators, including cortisol, which enhances resistance to stress by mitigating physiological changes induced by various stressors.

Of particular interest are two adaptogenic plants, W. somnifera (Ashwagandha) and R. rosea, both of which have been shown to influence the gut–brain axis, contributing to improved stress and mental health outcomes. These effects are believed to stem from their immunomodulatory and anti-inflammatory properties, which support gut homeostasis. Ashwagandha is generally considered a safe adaptogen and has been shown to reduce perceived stress and cortisol levels, exert anxiolytic effects, and alleviate stress and anxiety symptoms, including in conditions such as anxiety and bipolar disorder. However, the degree of effectiveness varies across studies, depending on factors such as dosage, population characteristics, and study design. Similarly, while R. rosea has been associated with reductions in self-reported anxiety and stress, and demonstrated anxiolytic properties as well as cortisol modulation, the consistency of these effects is not uniform.

Taken together, existing evidence suggest that psychobiotics and adaptogens may contribute to the regulation of stress- and anxiety-related symptoms through mechanisms such as cortisol and corticosterone modulation and regulation of the HPA axis. Nevertheless, the variability in findings reflects the heterogeneity of current research designs, populations, and outcome measures. As the application of psychobiotics and adaptogens in the treatment of stress- and mood-related disorders is still emerging, further investigation is required to better understand their efficacy, underlying mechanisms, and potential therapeutic value.

The objective of this systematic review is to assess the efficacy of alternative interventions—namely psychobiotics and adaptogens—in alleviating stress-related psychophysiological symptoms. Specifically, the review aims to determine whether these compounds lead to measurable improvements in stress and anxiety outcomes. In addition to this primary goal, a secondary aim is to identify the specific bacterial strains and herbal compounds most consistently associated with beneficial effects, thereby contributing to a more precise understanding.