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<p>According to the “Old Friends” hypothesis, the increased prevalence of stress-associated disorders in urban concrete landscapes of high-income countries is at least in part due to a reduced exposure to immunoregulatory microorganisms. The latter is particularly impactful when occurring during early prenatal and postnatal life. Accordingly, our own preclinical studies demonstrate that non-pathogenic rapid-growing mycobacteria, including <i>Mycobacterium (</i><i>M.) vaccae</i> NCTC 11659 and <i>M. vaccae</i> ATCC 15483<sup>T</sup>, have immunoregulatory and stress-protective effects when administered repeatedly prior to or during stressor exposure. Here, we advance these findings by showing that repeated intragastric (i.g.) administration of a heat-killed preparation of <i>M. vaccae</i> ATCC 15483<sup>T</sup> to female C57BL/6 N mice provides intergenerational stress protection. Their male offspring, despite never directly receiving administration of rapid-growing mycobacteria, were protected against multiple adverse consequences of chronic stress in adulthood. Moreover, correlational analyses implicate the fecal microbiome as a&#xa0;potential mediator of these effects, with <i>M. vaccae</i> ATCC 15483<sup>T</sup> intergenerationally facilitating α-diversity and increasing the relative abundance of bacterial taxa known to be potent short-chain fatty acid producers.</p><p></p>

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Microbial Legacy: Mycobacterium vaccae ATCC 15483T intergenerationally diversifies the microbiome and enhances stress resilience in male mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月22日

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  • Jessica Schiele,
  • Pei-Ling Tsai,
  • Tamara Schimmele,
  • Sina Beck,
  • Maren Meyer,
  • Marco Mannes,
  • Luke W. Desmond,
  • Reiner Noschka,
  • Markus Huber-Lang,
  • Melanie Haffner-Luntzer,
  • Marc N. Jarczok,
  • Christopher A. Lowry,
  • Andreas Reif,
  • Dominik Langgartner,
  • Steffen Stenger,
  • David A. Slattery,
  • Stefan O. Reber

摘要

According to the “Old Friends” hypothesis, the increased prevalence of stress-associated disorders in urban concrete landscapes of high-income countries is at least in part due to a reduced exposure to immunoregulatory microorganisms. The latter is particularly impactful when occurring during early prenatal and postnatal life. Accordingly, our own preclinical studies demonstrate that non-pathogenic rapid-growing mycobacteria, including Mycobacterium (M.) vaccae NCTC 11659 and M. vaccae ATCC 15483T, have immunoregulatory and stress-protective effects when administered repeatedly prior to or during stressor exposure. Here, we advance these findings by showing that repeated intragastric (i.g.) administration of a heat-killed preparation of M. vaccae ATCC 15483T to female C57BL/6 N mice provides intergenerational stress protection. Their male offspring, despite never directly receiving administration of rapid-growing mycobacteria, were protected against multiple adverse consequences of chronic stress in adulthood. Moreover, correlational analyses implicate the fecal microbiome as a potential mediator of these effects, with M. vaccae ATCC 15483T intergenerationally facilitating α-diversity and increasing the relative abundance of bacterial taxa known to be potent short-chain fatty acid producers.