Probiotics are live microorganisms, which when administered in adequate amounts present a health benefit for the host. While the beneficial effects of probiotics on gastrointestinal function are generally well recognized, new animal research and clinical studies have found that alterations in gut microbial communities can have a broad range of effects throughout the body. Non-intestinal sites impacted include the immune, endocrine, cardiovascular and the central nervous system (CNS). In particular, there has been a growing interest and appreciation about the role that gut microbiota may play in affecting CNS-related function through the ‘microbiota-gut-brain axis’. Emerging evidence suggests potential therapeutic benefits of probiotics in several CNS conditions, such as anxiety, depression, autism spectrum disorders and Parkinson’s disease. There may also be some gender-specific variances in terms of probiotic mediated effects, with the gut microbiota shaping and being concurrently molded by the hormonal environment governing differences between the sexes. Probiotics may influence the ability of the gut microbiome to affect a variety of biological processes in the host, including neurotransmitter activity, vagal neurotransmission, generation of neuroactive metabolites and inflammatory response mediators. Some of these may engage in cross talk with host sex hormones, such as estrogens, which could be of relevance in relation to their effects on stress response and cognitive health. This raises the possibility of gender-specific variation with regards to the biological action of probiotics, including that on the endocrine and central nervous systems. In this review we aim to describe the current understanding in relation to the role and use of probiotics in microbiota-gut-brain axis-related dysfunction. Furthermore, we will address the conceptualization and classification of probiotics in the context of gender and lifespan as well as how restoring gut microbiota composition by clinical or dietary intervention can help in supporting health outcomes other than those related to the gastrointestinal tract. We also evaluate how these new learnings may impact industrial effort in probiotic research and the discovery and development of novel and more personalized, condition-specific, beneficial probiotic therapeutic agents.

益生菌是活的微生物，当以足够的量给药时，它对宿主的健康有益。虽然益生菌对胃肠功能的有益作用已广为人知，但新的动物研究和临床研究发现，肠道微生物群落的改变会对全身产生广泛的影响。受影响的非肠道部位包括免疫、内分泌、心血管和中枢神经系统 (CNS)。特别是，人们对肠道微生物群通过“微生物群-肠-脑轴”在影响中枢神经系统相关功能方面可能发挥的作用越来越感兴趣和赞赏。新出现的证据表明益生菌在几种中枢神经系统疾病中具有潜在的治疗益处，例如焦虑、抑郁、自闭症谱系障碍和帕金森病。在益生菌介导的作用方面也可能存在一些性别差异，肠道微生物群的形成和同时受到控制性别差异的荷尔蒙环境的影响。益生菌可能会影响肠道微生物群影响宿主体内多种生物过程的能力，包括神经递质活性、迷走神经传递、神经活性代谢物的产生和炎症反应介质。其中一些可能与宿主性激素（例如雌激素）发生交叉对话，这可能与它们对压力反应和认知健康的影响有关。这增加了益生菌生物作用（包括对内分泌和中枢神经系统的作用）的性别特异性差异的可能性。在这篇综述中，我们旨在描述目前对益生菌在微生物-肠-脑轴相关功能障碍中的作用和使用的理解。此外，我们将在性别和寿命的背景下讨论益生菌的概念化和分类，以及通过临床或饮食干预恢复肠道微生物群组成如何有助于支持与胃肠道相关的健康结果。我们还评估了这些新知识如何影响益生菌研究中的工业努力，以及发现和开发新的、更个性化的、特定条件的、有益的益生菌治疗剂。我们将在性别和寿命的背景下讨论益生菌的概念化和分类，以及通过临床或饮食干预恢复肠道微生物群组成如何有助于支持与胃肠道相关的健康结果。我们还评估了这些新知识如何影响益生菌研究中的工业努力，以及发现和开发新的、更个性化的、特定条件的、有益的益生菌治疗剂。我们将在性别和寿命的背景下讨论益生菌的概念化和分类，以及通过临床或饮食干预恢复肠道微生物群组成如何有助于支持与胃肠道相关的健康结果。我们还评估了这些新知识如何影响益生菌研究中的工业努力，以及发现和开发新的、更个性化的、特定条件的、有益的益生菌治疗剂。