PLMI Blog

The gut microbiome—a vast ecosystem of trillions of microorganisms with at least 1,000 diverse species—plays an integral role in governing overall health. This unique microbial community encodes for five million genes and is significant for modulating nearly every system in the body, integral for digestion, metabolism, immune, hormonal, and neurological health (1-3).

Colonization of the microbiome begins at birth and is influenced by mode of delivery, genetics, stress, infections, diet, medications, environment, and sleep—all of which shape microbiome development over time. Vaginal births provide early exposure to diverse beneficial microbes, such as Lactobacillus, Prevotella, or Sneathia spp., while infants born via C-section acquire microbes through skin to skin contact, including various Staphylococcus, Haemophilus, Enterobacter, and Veillonella species (4-5). Breastfeeding further enriches the infant microbiome with essential nutrients and immune-modulating factors (6). As children grow, various factors continue to influence the composition and diversity of the microbiome, with the microbiome shifting and diversifying throughout life and adulthood.

A Disruption of Microbial Homeostasis with Systemic Consequences

Dysbiosis refers to an imbalance in the gut microbiome, including composition and functions. It is marked by a reduction of beneficial microbes, an overgrowth of pathogenic organisms, and a reduction in overall microbial diversity. This alteration in microbial composition disrupts the homeostasis of the microbiome—compromising mucosal immunity, intestinal barrier function, and digestive processes—while inducing systemic inflammation. The impact of dysbiosis has been increasingly recognized in metabolic dysfunction, immune dysregulation, neuroinflammation, and increased susceptibility to a wide range of health conditions, underscoring the role dysbiosis plays in contributing to overall systemic imbalance and pathology (7).

Causes of Dysbiosis

Mounting research highlights several factors contributing to the etiology of dysbiosis. A recent 2024 study published in The Journal of Infection & Immunity outlined a key mechanism that supported gut microbiome homeostasis, and thereby also contributed to imbalance.

The availability of oxygen and other respiratory electron acceptors in the host environment was shown to have a profound influence on the health and balance of the gut microbiome. Dysbiosis is implicated to occur when this symbiotic balance is disrupted, driving changes in the host environment and therefore inducing alterations in microbiome composition (8). Poor sleep, chronic stress, frequent antibiotic use, an unhealthy diet, intestinal permeability, and infections can all contribute to the development of dysbiosis by shifting the systemic balance of the host.

Lifestyle Factors that Contribute to Dysbiosis

Diet – Ultra-processed foods (UPFs) disrupt gut microbiome composition and intestinal barrier integrity. Characterized by high levels of synthetic additives, emulsifiers, and low dietary fiber, UPFs have been associated with reduced microbial diversity, including a reduction in opportunistic microbiota, Akkermansia muciniphila and Faecalibacterium prausnitzii, and an enrichment of pro-inflammatory microbiota—hallmarks of dysbiosis.

This disturbed microbial state induces chronic low-grade inflammation, which can contribute to various health conditions. Moreover, dysbiosis induced by UPF consumption may also impede the gut-brain axis.

Refined carbs and sugars fuel problematic microbes while depriving beneficial bacteria. Diets low in fiber from plant-based foods hinder beneficial bacteria and reduce microbial diversity (9). This underscores the importance of nutrient density and diversity in one’s diet, including an abundance of plants and anti-inflammatory fats, as well as adequate amounts of fiber, fermented foods, and probiotics (10).

Poor Sleep – Research highlights a strong interrelationship between sleep disturbances and gut dysbiosis, suggesting that impeded sleep may trigger systemic imbalances that contribute to microbial disruptions. Poor sleep can disrupt the gut-immune-brain network, promoting conditions that favor dysbiosis. Indeed, chronic poor sleep can also induce dysbiosis, as evidenced in a 2025 study published in The Journal of Neuroscience (11). Compromised sleep in obstructive sleep apnoea syndrome has been found to contribute to gut microbiome alterations, with reduced alpha diversity and distinct microbial clustering observed in affected individuals (12). Chronic stress and inadequate sleep have also been shown to alter the gut microbiome composition, creating a feedback loop that can further exacerbate health issues.

Chronic Stress – Chronic stress exerts profound effects on gut health by altering GI function, reshaping microbiota composition, reducing diversity, and promoting dysbiosis through hormonal and neurological pathways. Chronic stress has been associated with marked reductions in Bacteroides, Lactobacillus, and Bifidobacterium. Prolonged, heightened stress disrupts the gut-brain axis (GBA), a dynamic pathway integrating neural, immune, metabolic, and endocrine signals, while causing overactivation and dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis. Stress-induced alterations can disrupt enteric nervous system activity, impede gut barrier integrity, increase intestinal permeability, and trigger systemic inflammation via translocation of microbial products, such as lipopolysaccharides (LPS)—mechanisms correlated with conditions including anxiety, depression, and IBS (13).

An emerging body of research echoes the compounding role stress has in perpetuating a positive feedback loop with dysbiosis, compromised immunity, and mental health. Findings reveal that chronic stress drives microbial dysbiosis and immune dysregulation via the neuro-endocrine-immune axis, increasing risk of autoimmune conditions in susceptible individuals with dysbiosis perpetuating a systemic autoimmune response (14-15).  In the context of rheumatoid arthritis, dysbiosis was shown to play a mechanistic role in disease progression, by disrupting immune tolerance and promoting pro-inflammatory cytokine activity. Altered abundances of Firmicutes, Bacteroidetes, and Proteobacteria and increased intestinal permeability were found in RA patients, believed to further drive systemic inflammation and autoimmunity, as evidenced in a 2025 study (16).

Another 2025 study echoed the role of stress in impacting bidirectional signaling between the gut and brain, involving neural, metabolic, hormonal, and immune pathways relative to traumatic brain injury (TBI). Findings from TBI models revealed that central nervous system (CNS) dysfunction drives intestinal and blood-brain barrier permeability, alters microbial composition, and increases systemic inflammation—factors that collectively reinforce a cycle of neuroinflammation-driven dysbiosis. The study also demonstrated how TBI disrupts these interconnected pathways, further perpetuating pathological feedback loops that contribute to sustained systemic imbalance and neuroinflammation (17). Stress is implicated as a mediating factor in TBI (18).

Infection – Emerging evidence suggests that gut dysbiosis plays a critical role in immune dysregulation and the persistent systemic inflammation observed in COVID-19 patients. A 2025 study comprising 124 hospitalized COVID-19 patients demonstrated that severe cases were marked by elevated interleukin-6 levels, underscoring the presence of widespread inflammatory responses (19). A notable reduction in gut microbial diversity was also correlated with disease severity, with specific microbial signatures, such as increased abundance of Mitsuokella and Granulicatella, observed in patients with greater physical symptoms and psychological distress.

Infections can disrupt gut microbiome balance by damaging intestinal tissues and immune cells, altering microbial composition, and triggering systemic inflammation. This imbalance may contribute to disease progression and long-term complications, underscoring the importance of the gut microbiome in immune modulation and systemic homeostasis (20).

These findings highlight the complex interplay between gut microbiota, immune responses, and neuropsychiatric symptoms, underscoring the value the microbiome has in governing important aspects of health.

Environment – Climate is believed to influence gut microbiota through a network of interacting pathways, wherein effects, including heat stress, dietary alterations, and increased pathogen exposure, may act synergistically to exacerbate microbial dysbiosis and impair host immunity. For such, elevated temperatures can enhance gut permeability and pathogen invasibility, while concurrent dietary deficiencies may compromise immune function, creating feedback loops that further destabilize microbial and immune homeostasis (21). Environmental exposure to pesticides, chemicals, and over-sanitization can also reduce beneficial microbial diversity.

A systematic review revealed that exposure to heavy metals, particularly arsenic, lead, and mercury, was associated with significant alterations in gut microbiota composition, contributing to dysbiosis. Notably, elevated levels of these metals were linked to an increased abundance of Collinsella, a genus associated with pathobiont behavior, intestinal permeability, oxidative stress, and heightened risk for inflammatory bowel disease and certain cancers. These findings underscore the potential of nutritional interventions to mitigate heavy metal-induced dysbiosis and its downstream health effects, while also being mindful of these connections (22).

While factors such as loneliness may further contribute to dysbiosis, close contact with our pets may favorably influence the composition of the microbiome by promoting the exchange of beneficial microbes, leading to increased microbial diversity and a reduction in pathogenic bacteria, as noted in a 2024 study. This microbial enrichment helps support microbiota homeostasis and may mitigate dysbiosis-related conditions such as inflammatory bowel disease and Clostridium difficile infections (23).

Engagement with nature can help support gut microbiome balance by promoting beneficial microbial shifts—including increased Roseburia abundance—and enhancing serotonin production in the gut. A structured nature-based program not only improved microbiota composition in children but also reduced stress and emotional reactivity, suggesting that nature exposure may help mitigate dysbiosis and support emotional and microbial resilience (24).

Supporting circadian rhythm balance with appropriate exposure to sunlight is also important for gut microbiome balance, as well as to mitigate stress, as evidenced in a recent 2024 study published in Cell Metabolism through various pathways (25).

Medication & Substances – Pharmacological factors play a critical role in disrupting gut microbial homeostasis. A growing body of evidence demonstrates that the use of antibiotics, NSAIDs, acid-suppressing agents, and hormonal contraceptives significantly alters gut microbial composition, leading to dysbiosis-associated conditions such as small intestinal bacterial overgrowth (SIBO) and endotoxemia. In fact, a recent study reported that all evaluated drug classes induced dysbiosis, underscoring the impact of commonly used medications on the gut microbiota (26).  Notably, antibiotics can greatly alter the composition of the microbiome, as evidenced by a 2025 study, with reductions in alpha diversity (27). Antibiotics disrupt the gut microbiota by indiscriminately eliminating beneficial bacteria alongside harmful pathogens, leading to reduced microbial diversity and the emergence of antibiotic-resistant strains, increasing risk for antibiotic-induced dysbiosis along with metabolic dysfunction, allergies, and asthma  (27-28).

Chronic alcohol consumption has also been shown to drive compositional shifts characterized by an overrepresentation of Gram-negative bacteria and a depletion of commensal, anti-inflammatory taxa, contributing to a proinflammatory microbial milieu (29). These findings highlight the profound influence of exogenous agents on gut ecosystem integrity and their potential to exacerbate systemic inflammation.

Microbiome Modulation for Systemic Health

The gut microbiome is a central mediator of health, influencing metabolic, endocrine, immune, and nervous system functions through complex host-microbe interactions. Dysbiosis can arise not only from chronic stress and immune and metabolic dysregulation but also from increased intestinal permeability and microbial endotoxin exposure, compounding systemic inflammation and susceptibility to illness.

A balanced microbiome is supported by foundational lifestyle factors—including nutrient-dense foods, quality sleep, connections with others, stress management, movement, time in various nature ecosystems, and even spending time with our four-legged companions. As this research continues to evolve, microbiome-targeted therapies and practices will continue to emerge, offering valuable tools for improving health with personalized, multi-omics approaches to dysbiosis that optimize health at the microbial level.

Join us on May 27th, from 5-7 pm PDT, for this compelling, upcoming webinar, Refining “Dysbiosis”: Using Big-Data Analysis and Novel Interventions. Jeffrey Bland, PhD, Tom Guilliams, PhD, and Michael Chapman, ND, will take a deeper dive into this impactful topic that underlies a host of health conditions.

References:

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