The need for reliable biomarkers to measure biological aging

The gap

Evidence profile

Sourced from the stated research gap and stated challenges and future-work section and future work of the source papers, classified as general, drawn from work published between 2025 and 2026, spanning 6 journals. Those papers have been cited 92 times in total.

Supporting evidence — 8 representative gaps

• Gut Microbiota and Brain Aging: Identifying Keystone Biomarkers for Cognitive Health (2026) · Biomedicines · doi

  The need for reliable biomarkers to measure biological aging. The lack of understanding of the mechanisms connecting intestinal dysbiosis, dysfunction of the blood-brain barrier, neuroinflammation, and age-related cognitive decline. The need for effective interventions for the prevention and management of age-related cognitive decline.

  generalstated research gap
  Keywords: need reliable biomarkers measure biological aging lack understanding
• The Gut Microbiome and Its Impact on Mood and Decision-Making: A Mechanistic and Therapeutic Review (2025) · Nutrients · cited 18× · doi

  The complexity of the gut-brain axis and the need for a comprehensive understanding of the mechanisms and therapeutic perspectives. The need for causal routes and biological bridges between gut-derived signals and decision-making processes. The challenge of translating findings from preclinical studies to clinical applications, including the development of effective microbiome-targeted therapies.

  generalstated challenges
  Keywords: complexity gut-brain axis need comprehensive understanding mechanisms therapeutic
• The Oral–Gut Microbiome–Brain Axis in Cognition (2025) · Microorganisms · cited 59× · doi

  One of the challenges is understanding the complex interactions between the oral microbiome, gut microbiome, and brain. Another challenge is elucidating the mechanisms by which oral microbiome dysbiosis contributes to cognitive decline. A further challenge is developing targeted therapies to restore microbial balance and improve health outcomes.

  generalstated challenges
  Keywords: one challenges understanding complex interactions between oral microbiome
• The Role of Swine Gut Microbiota and Its Metabolites in Maintaining Intestinal Barrier Integrity and Mitigating Stress via the Gut–Brain Axis (2025) · Animals · cited 7× · doi

  The current understanding of the gut-brain axis and its regulation by the gut microbiota is limited. There is a need for further research on the role of the gut microbiota in maintaining intestinal barrier integrity and mitigating stress. The development of probiotic and nutritional programs tailored to the health status of the herd, the age of the animals, and environmental conditions is necessary.

  generalstated research gap
  Keywords: current understanding gut-brain axis regulation gut microbiota limited
• Gut Microbiota and Brain Aging: Identifying Keystone Biomarkers for Cognitive Health (2026) · Biomedicines · doi

  Further studies are needed to establish a cause-and-effect relationship between microbiome changes and cognitive decline - Research on microbiome-based interventions, including probiotics, prebiotics, dietary changes, fecal microbial transplant, and new treatment modalities derived from molecular studies - Investigation of the potential of the gut microbiota and its derived metabolites to promote longevity through immune modulation, neuroprotection, and metabolic support

  generalfuture-work section
  Keywords: further studies needed establish cause-and-effect relationship between microbiome
• Age-Related Changes in Gut Health and Behavioral Biomarkers in a Beagle Dog Population (2025) · Animals · cited 8× · doi

  Further research is needed to better understand the mechanisms and specific pathways involved in the relationship between the studied biomarkers and age, - Studies examining the relationship between intestinal microbiota and various pathologies are needed, - Research on the gut microbiome related to specific 'biotic' supplements and different diets composition is necessary

  generalfuture-work section
  Keywords: further research needed better understand mechanisms specific pathways
• Paradigm Shift of Microbiota-gut-brain Axis During Aging: Potential Role of Probiotics to Improve Cognitive Decline (2026) · Probiotics and Antimicrobial Proteins · doi

  The growing body of evidence solidifies a fundamental shift in our understanding of brain health: we can no longer view the brain as an isolated organ. Its function and resilience are deeply entwined with the state of the gut microbiome, forming a dynamic, bidirectional communication system, the gut-brain axis. While aging and genetics set the stage, the modifiable factors of diet, physical activity, and envi- ronmental exposures have the greater power in maintaining 1 3Probiotics and Antimicrobial Proteins a state of eubiosis. This grants us significant agency, trans- forming daily lifestyle choices into preventive medicine for the brain. The implications for neurodegenerative and neuropsy- chiatric disorders are profound. Dysbiosis acts as a slow- burning fuse, contributing to the pathogenesis of age-related diseases by compromising the very barriers meant to protect the brain and by priming glial cells for a harmful inflamma- tory response. The promise of targeting this axis is immense, as it moves us beyond merely managing symptoms to the potential of slowing disease progression. The potential use of specific microbial signatures as early diagnostic biomark- ers could revolutionize our approach, allowing for interven- tions decades before clinical symptoms manifest. Currently, the most immediate application is in the realm of mental health, where specific probiotic strains have earned their place as adjunctive or even stand-alone therapies for mild-to-moderate depression. This represents a critical step towards destigmatizing mental healthcare and integrating holistic, multi-system approaches. However, the path forward is fraught with complexity. The stark gap between compelling preclinical models and inconsistent human trials highlights a critical limitation: the human microbiome is a complex ecosystem, not a simple machine. Introducing a single probiotic strain is akin to introducing one new plant into a vast, established forest; the outcome depends on a multitude of pre-existing conditions. Therefore, future research must abandon a one-size-fits-all approach. The mantra must be strain-specific, condition- specific, and host-specific. We must move from simply asking “Do probiotics work?” to meticulously answering “Which specific bacterial strain, at what dose, in which formulation (including prebiotics), works for which indi- vidual, with which specific condition?” This necessitates a new generation of rigorous, large-scale clinical trials that embrace this complexity. Furthermore, we must look beyond live probiotics. Future research on perspectives must invest more seriously in the exploration of postbiotics, the inanimate microorgan- isms and their beneficial components. These defined, stable, and safe compounds could overcome the challenges of live culture delivery,

  generalfuture workevidence 5/5
  Keywords: specific brain must probiotics strain health state microbiome forming system axis beyond symptoms potential approach
• Restoring NAD+ pathways in brain aging and neurodegenerative diseases: roles of vitamin B3 metabolites, gut microbiota, and exercise in cognitive health (2026) · Frontiers in Nutrition · doi

  and evidence-based, Future research on NAD+ biology and brain aging should move beyond demonstrating biological effects toward establishing clinically meaningful, individualized therapeutic strategies. A major priority will be the development of precision medicine approaches capable of identifying likely to benefit from NAD+- individuals who are most enhancing interventions. Patient stratification based on age, genetic background, metabolic status, baseline NAD+ availability, disease stage, and molecular profiles may improve therapeutic targeting and help explain the heterogeneous responses observed in current clinical studies. An important emerging area involves understanding the interaction between NAD+ metabolism and the gut–brain axis. Although preclinical evidence suggests that microbiome composition may influence NAD+ metabolism, inflammation, and neuroactive metabolite production, the clinical relevance of microbiome-directed NAD+ interventions remains largely hypothetical and requires validation in well- controlled human studies. Future studies should clarify whether

  generalfuture workevidence 5/5
  Keywords: evidence based future brain therapeutic interventions clinical metabolism microbiome biology aging move beyond demonstrating biological

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