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<p>Depression is a common mood disorder that affects individuals across all age groups. Increasing evidence highlights the gut–brain axis as a critical contributor to its pathophysiology. Notably, depression differs in prevalence, clinical features, and underlying mechanisms across ages. To investigate whether gut microbiota contributes to these differences, comparative analyses across age groups are needed. In this study, we examined gut microbiota composition and functional alterations in younger adults (N = 43, aged 18–35) and older adults (N = 74, aged ≥ 60) with depression, using publicly available metagenomic datasets. Our findings highlight microbial shifts in dominant bacterial phyla such as Bacteroidota and Bacillota, which are strongly implicated in depression. Furthermore, alterations in metabolism and membrane transport pathways may affect oxidative stress, neurochemical balance, and hypothalamic–pituitary–adrenal (HPA) axis regulation, all of which play critical roles in the pathophysiology of depression. However, the absence of age-matched healthy controls and confounding factors such as diet, medication, lifestyle, and ethnicity limits the ability to predict these changes specifically to depression. Despite these limitations, our study underscores the importance of considering age when investigating gut–brain interactions in depression and highlights the need for multi-centric studies to validate age-dependent microbial and functional alterations and their clinical relevance.</p>

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Younger and older adults with major depressive disorder exhibit differential gut microbiome and gut-brain axis features

  • 期刊论文

  • 发表日期：

    2025年11月15日

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  • Robita Doley,
  • Kabyashree Bhuyan,
  • Quinat Tasneem Rafique,
  • Vijay Gogoi,
  • Pankaj Barah

摘要

Depression is a common mood disorder that affects individuals across all age groups. Increasing evidence highlights the gut–brain axis as a critical contributor to its pathophysiology. Notably, depression differs in prevalence, clinical features, and underlying mechanisms across ages. To investigate whether gut microbiota contributes to these differences, comparative analyses across age groups are needed. In this study, we examined gut microbiota composition and functional alterations in younger adults (N = 43, aged 18–35) and older adults (N = 74, aged ≥ 60) with depression, using publicly available metagenomic datasets. Our findings highlight microbial shifts in dominant bacterial phyla such as Bacteroidota and Bacillota, which are strongly implicated in depression. Furthermore, alterations in metabolism and membrane transport pathways may affect oxidative stress, neurochemical balance, and hypothalamic–pituitary–adrenal (HPA) axis regulation, all of which play critical roles in the pathophysiology of depression. However, the absence of age-matched healthy controls and confounding factors such as diet, medication, lifestyle, and ethnicity limits the ability to predict these changes specifically to depression. Despite these limitations, our study underscores the importance of considering age when investigating gut–brain interactions in depression and highlights the need for multi-centric studies to validate age-dependent microbial and functional alterations and their clinical relevance.