More than 20% of American adults live with a mental disorder, many of whom are treatment resistant or continue to experience symptoms. Other approaches are needed to improve mental health care, including prevention. The role of the microbiome has emerged as a central tenet in mental and physical health and their interconnectedness (well-being). Under normal conditions, a healthy microbiome promotes homeostasis within the host by maintaining intestinal and brain barrier integrity, thereby facilitating host well-being. Owing to the multidirectional crosstalk between the microbiome and neuro-endocrine-immune systems, dysbiosis within the microbiome is a main driver of immune-mediated systemic and neural inflammation that can promote disease progression and is detrimental to well-being broadly and mental health in particular. In predisposed individuals, immune dysregulation can shift to autoimmunity, especially in the presence of physical or psychological triggers. The chronic stress response involves the immune system, which is intimately involved with the gut microbiome, particularly in the process of immune education. This interconnection forms the microbiota-gut-immune-brain axis and promotes mental health or disorders. In this brief review, we aim to highlight the relationships between stress, mental health, and the gut microbiome, along with the ways in which dysbiosis and a dysregulated immune system can shift to an autoimmune response with concomitant neuropsychological consequences in the context of the microbiota-gut-immune-brain axis. Finally, we aim to review evidenced-based prevention strategies and potential therapeutic targets.

Dementia has rapidly become a major global health crisis. As the aging population continues to increase, the burden increases commensurately on both individual and societal levels. The behavioral and psychological symptoms of dementia (BPSD) are a prominent clinical feature of Alzheimer’s disease and related dementias (ADRD). BPSD represent a myriad of manifestations that can create significant challenges for persons living with dementia and their care providers. As such, BPSD can result in detriments to social interaction with others, resulting in harm to the psychosocial health of the person with dementia. While brain deterioration can contribute to BPSD as the disease progresses, it may be confounded by language and communication difficulties associated with ADRD. Indeed, when a person with dementia cannot effectively communicate their needs, including basic needs such as hunger or toileting, nor symptoms of pain or discomfort, it may manifest as BPSD. In this way, a person with dementia may be attempting to communicate with what little resources are available to them in the form of emotional expression. Failing to recognize unmet needs compromises care and can reduce quality of life. Moreover, failing to fulfill said needs can also deteriorate communication and social bonds with loved ones and caregivers. The aim of this review is to bring the differential of unmet needs to the forefront of BPSD interpretation for both formal and informal caregivers. The overarching goal is to provide evidence to reframe the approach with which caregivers view the manifestations of BPSD to ensure quality of care for persons with dementia. Understanding that BPSD may, in fact, be attempts to communicate unmet needs in persons with dementia may facilitate clinical care decisions, promote quality of life, reduce stigma, and foster positive communications.

Importance: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Multiple Sclerosis (MS).Observations: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer’s disease, followed by Parkinson’s disease, and then little in MS. The data for MS is encouraging despite this.Conclusions and relevance: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.

Alzheimer's disease (AD) is projected to become the highest‐burden neurological disorder globally. Mounting evidence implicates the gut microbiome in AD pathogenesis. This scoping review of gut microbiomes in mild cognitive impairment (MCI) and AD included dietary and probiotic interventions. We included original research and systematic reviews/meta‐analyses. Animal and non‐English studies were excluded. We searched PubMed, Scopus, and Cochrane Library through February 2023. Using Arksey and O'Malley's framework and the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA)‐Extension for Scoping Reviews (ScR) checklist, we screened 4751 articles, with 58 meeting predefined inclusion criteria. Our results demonstrated that gut dysbiosis was frequently reported in MCI and AD, including increased Pseudomonadota and Actinomycetota in AD and reduced diversity in some cases. Probiotic and dietary interventions showed promise in modulating cognition and microbiota, inconsistently. Emerging evidence links dysbiosis to cognitive decline; however, methodological heterogeneity and limited follow‐up impede causal inference. Research should prioritize standardized protocols, functional microbiome analysis, and longitudinal human studies to clarify therapeutic potential. Highlights: Gut dysbiosis is a common feature of MCI and AD, with phylum‐level microbial shifts frequently observed. Pseudomonadota and Actinomycetota are enriched in AD across multiple human studies. Beneficial genera like Faecalibacterium and Roseburia are consistently reduced in MCI and AD in a small number of studies. Probiotic and dietary interventions are promising to modulate the microbiota–cognition axis. More longitudinal human studies are needed to assess causal microbiome relationships.

As the aging population continues to increase, Alzheimer’s disease and related dementias are becoming a global health crisis. The burdens experienced by the person living with dementia, their caregivers, healthcare, and society persist unabated. Persons with dementia represent an important population in need of a tenable care plan. Caregivers need the tools with which to properly care for these persons and to mitigate their own stress response. A viable healthcare model utilizing integrated approaches to care for persons with dementia is in overwhelming demand. While much research is focused on a cure, it is equally important to address the difficulties faced by those currently affected. One approach is to incorporate interventions to increase quality of life within the caregiver-patient dyad via a comprehensive integrative model. Improving daily life of the persons with dementia, along with their caregivers and loved ones may aid in attenuating the pervasive psychological and physical impacts of this disease. A focus on interventions that provide neural and physical stimulation may facilitate quality of life in this regard. The subjective experience of this disease is challenging to capture. The relationship between neurocognitive stimulation and quality of life is at least, in part, therefore still uncertain. This narrative review aims to explore the efficacy and evidence-base of an integrative approach to dementia care in facilitating optimal cognition and quality of life outcomes. These approaches will be reviewed alongside person-centered care that is fundamental to integrative medicine, including exercise; music; art and creativity; nutrition; psychosocial engagement; memory training; and acupuncture.

Background: Sex and gender disparities persist across biomedical research, clinical care, and health policy, despite increasing recognition of sex-specific disease mechanisms and treatment responses. Underrepresentation of women in clinical trials continues to produce male-centric treatment protocols and insufficient data to support precision care. Methods: This narrative review applies a translational science framework to examine recurring and cross-cutting gaps in sex and gender health science. Rather than cataloging all disease areas, the review uses three exemplar domains—mental and neurological conditions, autoimmune disorders, and cardiovascular disease—to illustrate patterns observed across the research-to-policy continuum. Results: Findings reveal persistent issues including underrepresentation of women in research, inadequate sex-disaggregated data, and structural biases that impede equitable evidence development. These challenges appear consistently across basic science, clinical research, guideline development, and health policy translation. Conclusions: To advance equitable, evidence-based care, recommendations include adopting intersectional frameworks, improving sex-disaggregated data practices, increasing investment in sex-based research, and integrating sex and gender health science into medical education. Addressing these gaps through a translational lens is essential to achieving precision medicine that effectively serves all individuals.