Background: The equilibrium between gut microbiota (GM) and the host plays a pivotal role in maintaining overall health, influencing various physiological and metabolic functions. Emerging research suggests that exercise modulates the abundance and functionality of gut bacteria, yet the comprehensive effects on GM diversity remain to be synthesized. Objectives and Design: The study aims to quantitatively examine the effect of exercise on the diversity of gut microbiota of adults using a systemic review and meta-analysis approach. Methods: PubMed, Ebsco, Embase, Web of Science, Cochrane Central Register of Controlled Trials, the China National Knowledge Infrastructure, and Wanfang Data were searched from their inception to September 2023. Exercise intervention studies with a control group that describe and compare the composition of GM in adults, using 16S rRNA gene sequencing, were included in this meta-analysis. Results: A total of 25 studies were included in this meta-analysis with a total of 1044 participants. Based on a fixed-effects model [Chi² = 29.40, df = 20 (p = 0.08); I² = 32%], the pooled analysis showed that compared with the control group, exercise intervention can significantly increase the alpha diversity of adult GM, using the Shannon index as an example [WMD = 0.05, 95% CI (0.00, 0.09); Z = 1.99 (p = 0.05)]. In addition, exercise interventions were found to significantly alter GM, notably decreasing Bacteroidetes and increasing Firmicutes, indicating a shift in the Firmicutes/Bacteroidetes ratio. The subgroup analysis indicates that females and older adults appear to exhibit more significant changes in the Shannon Index and observed OTUs. Conclusions: Exercise may be a promising way to improve GM in adults. In particular, the Shannon index was significantly increased after exercise. Distinct responses in GM diversity to exercise interventions based on gender and age implicated that more research was needed.

Physical activity (PA) and quality sleep are essential for cognitive health, providing synergistic protection against age-related cognitive decline. However, the shared molecular pathways that explain their combined and interactive benefits remain poorly understood. This review suggests that lactate, long dismissed as a metabolic waste product, is a unifying mechanism. We introduce the “Lactate Nexus”, a conceptual framework that proposes lactate functions as a key signalling molecule, mechanistically linking the pro-cognitive effects of both daytime exercise and nighttime sleep. We begin by outlining lactate’s evolving role—from an energy substrate shuttled from astrocytes to neurons (the Astrocyte–Neuron Lactate Shuttle) to a pleiotropic signal. As a signal, lactate influences neuroplasticity via NMDA receptors, neuroinflammation via the HCAR1 receptor, and gene expression through the epigenetic modification of histone lactylation. We then compile evidence demonstrating how PA provides a substantial lactate signal that activates these pathways and primes the brain’s metabolic infrastructure. Crucially, we integrate this with proof that lactate levels naturally increase during slow-wave sleep to support memory consolidation and glymphatic clearance. The “Lactate Nexus” framework offers a comprehensive molecular explanation for the synergy between PA and sleep, positioning lactate as a key signalling mediator and a promising biomarker and therapeutic target for fostering lifelong cognitive resilience.

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