PLMI Blog

The gut microbiome governs central homeostatic functions in the body, having profound effects on health. This diverse and complex ecosystem harbors densely populated communities of microbiota, viruses, fungi, and archaea—with each having integral roles in collectively modulating host physiology. Eubiosis describes harmonious balance among these vast interspecies of microorganisms, while dysbiosis refers to a disturbance in this delicate balance, which may include reduced diversity, altered composition, and functional metabolic activity.

Dysbiosis has emerged as a key driving factor in the pathogenesis of a wide spectrum of chronic health conditions—underscoring the regulatory roles the gut microbiome exerts on maintaining health and mitigating illness (1).

The Dynamic & Complex Microbiome Ecosystem

The collective functionality of the microorganisms residing in the microbiome is pivotal for modulating immune, metabolic, and hormonal functions, as well as governing levels of inflammation, epithelial and gut barrier integrity, and driving biosynthesis of key metabolites that support health—including neurotransmitters and short-chain fatty acids (SCFAs). In fact, the gut microbiome synthesizes 30 neurotransmitters, hosts nearly 1000 diverse microbial species, and encodes for five million genes (2).

Dysbiosis is now understood to exert far-reaching effects beyond the gut, including immune and metabolic dysregulation, disruptions in neuroendocrine signaling, epithelial barrier function, and systemic inflammation, and impeding neurochemical balance.

Beneficial commensals (including genera Bacteroides, Bifidobacterium, Prevotella, Ruminococcus, Roseburia, Akkermansia muciniphila, Lactobacillus, and Clostridium spp.) live in a symbiotic relationship with the host, contributing to epithelial resilience, mucosal immunity, and metabolic regulation through short-chain fatty acid (SCFA) production and immune tolerance mechanisms. In contrast, dysbiosis is characterized by overrepresentation or pathogenic activation of taxa, including Clostridioides difficile, Fusobacterium nucleatum, Helicobacter pylori, Salmonella, and enterohemorrhagic E. coli. These strains of bacteria have been implicated in epithelial disruption, chronic inflammation, and disease progression.

Microbial imbalances—driven by lifestyle, dietary, environmental, pharmaceutical, or host genetic factors—can initiate a cascade of dysregulated immune responses and metabolic disturbances. Mounting evidence demonstrates the role of gut dysbiosis in the pathophysiology of autoimmune, neuropsychiatric, neurodegenerative, metabolic, skin, and cardiovascular conditions.

Dysbiosis Further Drives Systemic Imbalance

Dysbiosis alters microbial metabolism and signaling in ways that actively destabilize core physiological systems. The depletion of beneficial taxa diminishes the production of short-chain fatty acids (SCFAs) and other metabolites essential for maintaining gut barrier integrity, appropriate immune response, and metabolic flexibility. Simultaneously, overgrowth of opportunistic organisms increases the production of endotoxins and pro-inflammatory metabolites that can permeate the gut lining and enter circulation.

This toxic synergy disrupts mucosal immunity and weakens epithelial barriers, creating a leaky gut environment or intestinal permeability, allowing microbial products to provoke systemic inflammation. In turn, these inflammatory signals disrupt hormonal pathways, alter insulin sensitivity, impede neurotransmitter balance, and further compromise immune regulation. This results in a vicious cycle in which microbial imbalance drives physiological imbalance and vice versa, fueling the pathogenesis of autoimmune, metabolic, neuropsychiatric, and inflammatory conditions through these systemic mechanisms (1-3).

Gut Dysbiosis & Immune Dysregulation

Approximately 70–80% of the body’s immune system is housed in the gut-associated lymphoid tissue (GALT) (4). The balance of microbial antigens within this ecosystem directly shapes the tone and reactivity of immune responses. Dysbiosis can trigger persistent low-grade inflammation through the overrepresentation of pro-inflammatory microbes and the loss of immune-modulating commensals. Notably, the translocation of bacterial components, such as lipopolysaccharides (LPS), across a weakened gut barrier can result in metabolic endotoxemia. This process activates toll-like receptor 4 (TLR4) pathways, triggering systemic inflammation. Elevated markers, including interleukin-6 (IL-6) and interleukin-1-alpha (IL-1α), have been consistently observed in individuals with dysbiosis-associated disorders, including metabolic syndrome, autoimmune conditions, and cardiovascular disease (5-6).

Intestinal Permeability & Systemic Inflammation

The integrity of the gut epithelial barrier is essential for maintaining immune and metabolic health. Dysbiosis contributes to epithelial damage through microbial metabolite imbalances—such as reduced short-chain fatty acids (SCFAs) and increased proteolytic fermentation byproducts—which impair tight junction proteins. The resulting “leaky gut” facilitates the entry of microbial toxins into systemic circulation, provoking immune activation and inflammatory cascades across organ systems. This mechanism underpins associations between gut dysbiosis and chronic inflammatory diseases, such as inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and even complications from viral infections, such as COVID-19 (7-8).

Neuroinflammation & the Gut-Brain Axis

The microbiota-gut-brain axis facilitates bidirectional communication between the gastrointestinal (GI) system and central nervous system (CNS) via neural (vagus nerve), endocrine (hypothalamic-pituitary-adrenal/HPA axis), immune, and metabolic pathways. Gut microbes synthesize and modulate neuroactive compounds, including serotonin, dopamine, and gamma-aminobutyric acid (GABA), as well as SCFAs that influence blood-brain barrier integrity and microglial function. Dysbiosis disrupts this axis, contributing to neuroinflammation, neurotransmitter imbalance, and increased permeability of the blood-brain barrier (9-10).

Recent reviews have demonstrated correlations between gut dysbiosis and psychiatric and neurodevelopmental conditions, including depression, anxiety, ADHD, and autism spectrum disorders (ASD) (11-13). Adolescents with depression, for instance, were found to exhibit reduced alpha diversity, with an increased abundance of pro-inflammatory genera, such as Streptococcus, and decreased protective genera, such as Faecalibacterium. These microbial alterations are associated with elevated inflammatory cytokines and altered tryptophan metabolism, revealing potential diagnostic biomarkers and intervention targets (13).

Moreover, dysbiosis has been implicated in neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Studies suggest that altered microbial metabolites, such as trimethylamine-N-oxide (TMAO), indoles, and branched-chain amino acids, can exacerbate amyloid pathology, tauopathy, and alpha-synuclein aggregation—key hallmarks of these disorders (9, 14-15).

Endocrine & Hormonal Implications

The estrobolome—a subset of gut bacteria that modulate estrogen metabolism—plays a crucial role in hormonal homeostasis. Dysbiosis impedes activity of β-glucuronidase-producing bacteria, leading to dysregulated estrogen recycling, which may contribute to estrogen dominance, menstrual irregularities, endometriosis, and even estrogen-sensitive cancers (16). Additionally, reduced SCFA levels impair insulin sensitivity and adiponectin signaling, promoting hormonal and metabolic dysfunction (6).

Metabolic Dysfunction & Cardiovascular Risk

Dysbiosis alters the production and absorption of microbial metabolites critical to host energy regulation, such as SCFAs (butyrate, propionate, acetate). These molecules support glucose homeostasis, mitochondrial function, and appetite signaling. Reduced SCFA-producing bacteria, such as Faecalibacterium and Roseburia, are consistently observed in individuals with insulin resistance, type 2 diabetes, and obesity (16). Furthermore, dysbiosis increases circulating levels of atherogenic metabolites, including TMAO and indoxyl sulfate, which promote vascular inflammation and endothelial dysfunction—key precursors of cardiovascular disease (6).

Autoimmunity & Dysregulated Immune Tolerance

The gut microbiome promotes immune tolerance by actively training regulatory T cells (Tregs) and modulating antigen presentation, thereby shaping immune response.

Disruptions in microbial diversity and SCFA production contribute to immune dysregulation implicated in autoimmune conditions. A recent meta-analysis involving over 6,000 subjects revealed consistent patterns of reduced microbial diversity and increased pro-inflammatory taxa in patients with autoimmune neurological diseases, such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder, and autoimmune encephalitis (17). Reductions in beneficial SCFA-producing bacteria, including Faecalibacterium and Roseburia, with increases in pathogenic genera, such as Streptococcus and Escherichia-Shigella, were observed.

Similarly, Systemic Lupus Erythematosus (SLE) patients were demonstrated to exhibit gut dysbiosis, marked by reduced microbial richness and altered metabolite production, contributing to systemic inflammation, immune activation, and organ damage (8).

Gut-Skin Axis & Dermatological Health

The gut-skin axis represents the bidirectional communication between the gastrointestinal tract and skin via immune, microbial, and neuroendocrine signaling. Dysbiosis disrupts this axis, often manifesting in inflammatory skin conditions. Atopic dermatitis (AD), for example, is associated not only with skin microbiota imbalances but also with reduced SCFA-producing gut microbes and increased intestinal permeability (18-19). This promotes systemic immune activation that may exacerbate cutaneous inflammation. Marked reductions in beneficial microbial diversity and overgrowth of Staphylococcus aureus have been observed in AD patients, which has been associated with compromised skin barrier function and immune dysregulation.

In conditions such as rosacea and hidradenitis suppurativa, reduced gut microbial diversity and imbalances in commensal-pathogen ratios have also been observed. The correlation between dysbiosis and rosacea is suggested to involve several organisms, including Demodex spp., Bacillus oleronius, S. epidermidis, and Cutibacterium acnes. Compared to healthy or non-lesional skin, HS lesions also exhibited reduced Cutibacterium acnes and increased relative abundance of anaerobic bacteria, including Peptoniphilus, Prevotella, Porphyromonas, and Corynebacterium species.

Therapeutic interventions targeting the gut microbiome—such as probiotics, prebiotics, and even fecal microbiota transplantation (FMT)—show promise in restoring cutaneous and systemic homeostasis (20).

Dysbiosis and Infection Outcomes: COVID-19

Acute infections, including SARS-CoV-2 have been shown to induce or exacerbate gut dysbiosis, which can impede recovery and contribute to long COVID symptoms. In COVID-19 patients, reduced microbial diversity and overgrowth of pathogenic taxa have been linked to systemic inflammation, increased disease severity, and prolonged gastrointestinal (GI) symptoms. Analysis of alpha diversity using the Shannon index demonstrated a significant decrease in gut microbiota diversity among critically ill COVID-19 patients, compared to those with milder disease severity. Species richness, assessed by the Chao1 index, was notably lower in critically ill patients compared to those with low and moderate disease severity. Notably, in patients with mild disease severity, Streptococcus periodonticum and Clostridium perfringens were relatively enriched, whereas critically ill individuals demonstrated increased abundance of Klebsiella pneumoniae and Prevotella loescheii (7).

Restoring gut microbial balance, therefore, may offer supportive benefits in post-viral recovery and beyond.

Functional Medicine Applications & Future Implications

Understanding the centrality of the gut microbiome in health and disease opens novel pathways for diagnosis, prevention, and treatment. Being mindful of lifestyle factors—including diet, stress, sleep, and movement—is significant for reducing dysbiosis. Sleep and stress are particularly valuable in maintaining equilibrium in the gut microbiome (21-22).  Personalized dietary plans (e.g., Mediterranean diet, low-FODMAP), supplementation with targeted prebiotics and probiotics, intermittent fasting, and microbiome restoration therapies (e.g., FMT) can help re-establish microbial harmony (9-10). Various functional lab tests to assess diversity and composition of the gut microbiome ecosystem can also be employed that screen for patterns of commensal and pathogenic bacteria.

Gut dysbiosis is not solely a localized gastrointestinal disturbance—it is a systemic disruptor of balance with implications for nearly every organ system. From neurological health to metabolism and immunity, the downstream effects of microbial imbalance are vast and profound.

Join us for this free, compelling, and valuable webinar, occurring on May 27th: Refining “Dysbiosis”: Using Big-Data Analysis and Novel Interventions from 5–7 PM PDT, with leading experts: Dr. Jeffrey Bland, Dr. Tom Guilliams, and Dr. Michael Chapman. This event will delve into cutting-edge clinical insights on the evolving concept of dysbiosis—emphasizing the application of evidence-based and innovative therapeutic strategies to develop more targeted, effective, and transformative treatment protocols.

References:

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