Autoimmune (AI) diseases, which present in a multitude of systemic manifestations, have been connected to many underlying factors. These factors include the environment, genetics, individual microbiomes, and diet. An individual’s gut microbiota is an integral aspect of human functioning, as it is intimately integrated into the metabolic, mechanical, immunological, and neurologic pathways of the body. The microbiota dynamically changes throughout our lifetimes and is individually unique. While the gut microbiome is ever-adaptive, gut dysbiosis can exert a significant influence on physical and mental health. Gut dysbiosis is a common factor in various AI, and diets with elevated fat and sugar content have been linked to gut microbiome alterations, contributing to increased systemic inflammation. Additionally, multiple AI’s have increased levels of certain inflammatory markers such as TNF-a, IL-6, and IL-17 that have been shown to contribute to arthropathy and are also linked to increased levels of gut dysbiosis. While chronic inflammation has been shown to affect many physiologic systems, this review explores the connection between gut microbiota, bone metabolism, and the skeletal and joint destruction associated with various AI, including psoriatic arthritis, systemic lupus erythematosus, irritable bowel disease, and rheumatoid arthritis. This review aims to define the mechanisms of microbiome crosstalk between the cells of bone and cartilage, as well as to investigate the potential bidirectional connections between AI, bony and cartilaginous tissue, and the gut microbiome. By doing this, the review also introduces the concept of altering an individual’s specific gut microbiota as a form of regenerative medicine and potential tailored therapy for joint destruction seen in AI. We hope to show multiple, specific ways to target the microbiome through diet changes, rebalancing microbial diversity, or decreasing specific microbes associated with increased gut permeability, leading to reduced systemic inflammation contributing to joint pathology. Additionally, we plan to show that diet alterations can promote beneficial changes in the gut microbiota, supporting the body’s own endogenous processes to decrease inflammation and increase healing. This concept of microbial alteration falls under the definition of regenerative medicine and should be included accordingly. By implementing microbial alterations in regenerative medicine, this current study could lend increasing support to the current research on the associations of the gut microbiota, bone metabolism, and AI-related musculoskeletal pathology.

Chronic psychological stress is known to influence immune function and contribute to development of autoimmune disorders through dysregulated inflammatory responses. This study investigates relationships between acute stress, life trauma, and autoimmune salivary biomarkers in firefighter recruits during psychophysical stress training. Salivary samples were collected from firefighter recruits during two stress tests to evaluate responses to acute stress. Samples were obtained at three time points—pre-stress, post-stress, and recovery—across both tests. Cortisol was measured to characterize acute stress response (ASR) profiles, while immune function was assessed through the analyzing C-reactive Protein (CRP), Complement C4 (C4), Pigment Epithelium Derived Factor (PEDF), and Serum Amyloid P (SAP). Results showed significant changes in CRP, C4, and PEDF after stress inoculation. Higher previous life trauma was associated with lower baseline cortisol (r = −0.489) and delay in cortisol recovery (r = 0.514), suggesting a learned biological response, potentially protective against stress-induced dysregulation. Cluster analysis revealed four distinct cortisol ASR profiles which were found to have significantly different past life trauma (p = 0.031). These findings suggest that trauma history influences stress biomarker dynamics, potentially reflecting individualized adaptive or maladaptive responses. The insights gained may inform strategies to enhance stress resilience and mitigate autoimmune risk among high-stress populations.