Some of our body's microbes induce psychological stress, while other microbes enhance our resilience to it. This is the central hypothesis of the article in this issue by Aktipis and Guevara Beltran,^[1] along with the proposition that these variable microbial communities derive great evolutionary benefit from their unique relationships with us as their naïve host. There is growing evidence for the relationship of stress with the composition and diversity of the microbiome, although the causal direction of this relationship and its underlying mechanisms are not yet understood. The proposed hypotheses of this essay offer a novel perspective on potential processes that may explain these relationships. In general, the authors provide thought‐provoking support for their conjectures, and their formal hypothesis is congruent with previous literature that has discussed the concept of stress contagion as well as the role of host stress in the field of microbial pathogenesis. However, the authors extend and integrate previous stress‐related, microbial, and evolutionary concepts in creative ways.

Nevertheless, many of the premises on which the hypotheses are based warrant further study and development. First, much of the research cited is only associational, precluding the ability to determine directionality of the relationships or any causal effect. The authors include both literature indicating that stress induces microbial changes, and literature suggesting that microbes modulate stress. These different pathways need to be more carefully distinguished and studied in order to better understand the true role of the microbiome. Second, the authors use varied studies of stress, anxiety, depression and other types of psychological distress to support their hypotheses. Yet, these various emotional states have distinctive phenotypes and symptoms, with potentially different implications for their microbial relationships. More research is needed to identify microbial mechanisms that may have relevance across a variety of types of psychological distress, and those that may be unique to stress per se. Third, it is proposed that microbes can affect stress in three major ways: through activation of the vagus nerve (via the autonomic nervous system, ANS), through disruption of the hypothalamic‐pituitary‐adrenal (HPA) axis, and through mediation by the immune system. Aktipis and Guevara Beltram focus primarily on inflammatory changes; but each of these stress response systems represents major areas for further exploration. Studying the links between certain microbial strains and measures of heart rate variability during stress could shed light on relationships to the ANS, while examining associations between glucocorticoid response during stress and the functional and metabolic characteristics of the microbiome would inform our understanding of its relationship to the HPA axis. Lastly, the proposed idea that microbes manipulate human interactions by eliciting or reducing social engagement to enhance or limit microbial transmission is perhaps the most controversial and speculative component of the paper. If such effects occur, they likely involve complex dynamics that current research does not adequately address. Future studies in this area will require integrated, ecological momentary assessment that examines the interplay of psychological, social and microbial measures over time.

Regardless of these caveats, the article warrants a thorough perusal. The authors raise many stimulating and innovative ideas for our consideration. Central among these is the existence of ‘resilience microbes’ that help the host recover from stress‐related perturbations and maintain a stable environment. This notion is congruent with the concept of allostasis,^[2] whereby the body generates a variety of biological mediators (e.g., hormones, cytokines, increased heart rate) that help an individual adapt to novelty, challenge and environmental stressors. The microbiota likely serves as an additional allostatic mediator that facilitates adaptation to stress.^[3] Both resilience and allostasis imply a dynamic ability to recover from and adapt to disruptions or stressors with greater flexibility and ease. In contrast, ‘stress microbes’ are proposed to cultivate increased ANS, HPA, and inflammatory reactivity associated with greater stress. Chronic activation of such responses could lead to increased allostatic load (the cost incurred by exposure to elevated or fluctuating stress responses over time). Understanding the roles played by microbes in generating and attenuating human stress could be advanced substantially by conceptualizing and testing salient variables within a framework of allostasis and allostatic load.

我们体内的一些微生物会引起心理压力，而其他微生物则增强我们的抵御能力。这是 Aktipis 和 Guevara Beltran 在本期文章中的中心假设， ^{[ 1 ]}以及这些可变微生物群落从它们与我们作为其幼稚宿主的独特关系中获得巨大的进化益处的命题。越来越多的证据表明压力与微生物组的组成和多样性之间存在关系，尽管这种关系的因果方向及其潜在机制尚不清楚。本文提出的假设为可能解释这些关系的潜在过程提供了新颖的视角。总的来说，作者为他们的猜想提供了发人深省的支持，他们的正式假设与之前讨论应激传染概念以及宿主应激在微生物发病机制领域中的作用的文献是一致的。然而，作者以创造性的方式扩展和整合了之前的压力相关、微生物和进化概念。

然而，这些假设所依据的许多前提值得进一步研究和发展。首先，引用的大部分研究只是关联性的，无法确定关系的方向性或任何因果效应。作者收录了表明压力会引起微生物变化的文献，以及表明微生物调节压力的文献。需要更仔细地区分和研究这些不同的途径，以便更好地了解微生物组的真正作用。其次，作者利用对压力、焦虑、抑郁和其他类型的心理困扰的各种研究来支持他们的假设。然而，这些不同的情绪状态具有独特的表型和症状，对其微生物关系具有潜在的不同影响。需要更多的研究来确定可能与各种类型的心理困扰相关的微生物机制，以及那些可能与压力本身有关的微生物机制。第三，有人提出，微生物可以通过三种主要方式影响压力：通过激活迷走神经（通过自主神经系统，ANS），通过破坏下丘脑-垂体-肾上腺（HPA）轴，以及通过免疫系统。 Aktipis 和 Guevara Beltram 主要关注炎症变化；但这些压力反应系统中的每一个都代表了需要进一步探索的主要领域。 研究某些微生物菌株与压力期间心率变异性测量之间的联系可以揭示与 ANS 的关系，同时检查压力期间糖皮质激素反应与微生物组的功能和代谢特征之间的关联将有助于我们了解其与HPA 轴。最后，所提出的观点，即微生物通过引发或减少社会参与来增强或限制微生物传播来操纵人类互动，这可能是本文中最具争议性和推测性的部分。如果发生这种影响，它们可能涉及当前研究尚未充分解决的复杂动态。该领域的未来研究将需要综合的生态瞬时评估，以检查心理、社会和微生物措施随时间的相互作用。

不管这些警告如何，这篇文章都值得仔细阅读。作者提出了许多令人兴奋和创新的想法供我们考虑。其中最重要的是“弹性微生物”的存在，它可以帮助宿主从与压力相关的扰动中恢复并维持稳定的环境。这个概念与异稳态的概念一致， ^{[ 2 ]}身体产生各种生物介质（例如激素、细胞因子、心率增加），帮助个体适应新奇、挑战和环境压力。微生物群可能作为一种额外的调节介质，促进对压力的适应。 ^{[ 3 ]}弹性和平衡都意味着以更大的灵活性和轻松性从干扰或压力源中恢复和适应的动态能力。相比之下，“压力微生物”被认为可以培养与更大压力相关的 ANS、HPA 和炎症反应性。此类反应的慢性激活可能会导致非稳态负荷增加（随着时间的推移，暴露于升高或波动的应激反应而产生的成本）。通过在稳态和稳态负荷框架内概念化和测试显着变量，可以大大推进对微生物在产生和减轻人类压力中所发挥的作用的理解。