The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome’s influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota’s contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome’s variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.

Fusobacterium functions as both commensal and pathogen, linking the oral–gut axis to diverse diseases, including cancer. Evidence shows it modulates microbial balance, promotes dysbiosis, and contributes to carcinogenesis by driving inflammation, proliferation, invasion, and immune evasion. This review integrates ecological, molecular, and clinical insights, highlighting its roles in oral and systemic disease and discussing therapeutic potential, underscoring Fusobacterium’s dualistic nature and implications for microbiome-targeted interventions.

Background: The relationship between COVID-19 infection and a possible increased likelihood of older adults developing new-onset dementia (NOD) remains elusive. Methods: A thorough search was performed across several databases including MEDLINE/PubMed, PsycINFO, Scopus, medRxiv, and PQDT Global for studies published in English from January 2020 to December 2023. Only original investigations exploring the link between COVID-19 infection and NOD were selected for inclusion. We assessed the risk of developing NOD, using Risk Ratio (RR) for measurement. Control groups were categorized as: (i) a non-COVID cohort with other respiratory infections [control group (C1)]; and (ii) a non-COVID cohort with otherwise unspecified health status [control group (C2)]. Follow-up periods were divided into intervals of 3, 6, 12, and 24 months post-COVID. Results: 11 studies (involving 939,824 post-COVID-19 survivors and 6,765,117 controls) were included in the review. Across a median observation period of 12 months post-COVID, the overall incidence of NOD was about 1.82% in the COVID-infected group, compared to 0.35% in the non-COVID-infected group. The overall pooled meta-analysis showed a significantly increased NOD risk among COVID-19 older adult survivors compared to non-COVID-19 controls (RR = 1.58, 95% CI 1.21–2.08). Similar increased NOD risks were observed in subgroup analyses restricted to an observational period of 12 months (RR = 1.56, 95% CI 1.21–2.01), as well as in five studies that employed propensity score matching to sufficiently and effectively control for multiple confounding covariates (RR = 1.46, 95% CI 1.10–1.94). COVID-19 group and C1 group shared a comparably increased risk of developing NOD (overall RR = 1.13, 95% CI 0.92–1.38). Discussion: Under normal circumstances, we believe that COVID-19 infection is likely to be a risk factor for developing NOD in older adults over time. While the increased NOD risk due to COVID-19 infection appears to be similar to that associated with other respiratory infections, it warrants and necessitates investigation with longer observations.

The gut microbiome is increasingly recognized as a fundamental regulator of metabolic health, shaping energy balance, insulin sensitivity, inflammatory tone, and inter-organ communication through a broad spectrum of microbial metabolites that engage host signaling pathways. In this review, we synthesize current mechanistic insights into how gut microbial communities shape metabolic function, with particular emphasis on short-chain fatty acids, secondary bile acid signaling, gut barrier integrity, immune modulation, and the microbiota-gut-brain-pancreas axis. We further summarize disease-associated alterations in microbial composition and function across obesity, type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and metabolic syndrome, highlighting key microbial and metabolic features that contribute to metabolic dysfunction. Evidence from germ-free models, fecal microbiota transplantation studies, and strain-level interventions suggests that shifts in microbial ecology may causally shape metabolic outcomes. We also critically evaluate emerging microbiome-centered therapeutic strategies, including targeted probiotics, prebiotics, dietary modulation, and fecal microbiota transplantation, while addressing factors that underlie inter-individual variability in treatment responses. In addition, we discuss the growing influence of multi-omics technologies, microbial metabolic modeling, and machine learning approaches in advancing precision microbiome medicine. To integrate these advances within a coherent framework, we outline a precision microbiome intervention pipeline linking multidimensional profiling to functional stratification and targeted therapeutic design. We also introduce a conceptual Precision Microbiome Intervention Triangle to mechanistically explain heterogeneity in responses to microbiome-targeted therapies. Collectively, these insights establish and position the gut microbiome as both a mechanistic driver and a modifiable therapeutic target in metabolic disease, and highlight key challenges and future directions for the development of personalized microbiome-based metabolic interventions.

Background: Neurexins, essential synaptic proteins, are linked to neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD) and schizophrenia.Objective: Through this systematic review, we aimed to shed light on the relationship between neurexin dysfunction and its implications in neurodevelopmental and neuropsychiatric manifestations. Both animal and human-induced pluripotent stem cell (hiPSC) models served as our primary investigative platforms.Methods: Utilizing the PRISMA 2020 guidelines, our search strategy involved scouring articles from the PubMed and Google Scholar databases covering a span of two decades (2003–2023). Of the initial collection, 27 rigorously evaluated studies formed the essence of our review.Results: Our review suggested the significant ties between neurexin anomalies and neurodevelopmental and neuropsychiatric outcomes, most notably ASD. Rodent-based investigations delineated pronounced ASD-associated behaviors, and hiPSC models derived from ASD-diagnosed patients revealed the disruptions in calcium dynamics and synaptic activities. Additionally, our review underlined the integral role of specific neurexin variants, primarily NRXN1, in the pathology of schizophrenia. It was also evident from our observation that neurexin malfunctions were implicated in a broader array of these disorders, including ADHD, intellectual challenges, and seizure disorders.Conclusion: This review accentuates the cardinal role neurexins play in the pathological process of neurodevelopmental and neuropsychiatric disorders. The findings underscore a critical need for standardized methodologies in developing animal and hiPSC models for future studies, aiming to minimize heterogeneity. Moreover, we highlight the need to expand research into less studied neurexin variants (i.e., NRXN2 and NRXN3), broadening the scope of our understanding in this field. Our observation also projects hiPSC models as potent tools for bridging research gaps, promoting translational research, and fostering the development of patient-specific therapeutic interventions.

COVID-19 is associated with long-term neurological complications, but its impact on new-onset dementia (NOD), particularly vascular dementia (VaD) and Alzheimer’s disease (AD), remains unclear. We observed adults aged 50 years and older from the UK Biobank over a median observational period exceeding two years following COVID-19 infection. Incidences of various types of dementia (including all-cause dementia, AD, and VaD) in these individuals were compared with those in propensity-score-matched controls without COVID-19 and in individuals with non-COVID respiratory illnesses (including both non-communicable respiratory conditions and non-COVID respiratory tract infections). We found that COVID-19 survivors had a higher likelihood of developing NOD compared to uninfected controls. This increased risk was primarily driven by VaD rather than AD; however, the risk did not surpass that observed among individuals with non-COVID respiratory illnesses. Notably, individuals with pre-existing mental health conditions were particularly vulnerable, exhibiting significantly higher risks of VaD following COVID-19 infection.