Gut Dysbiosis miams

Clinic

• Dysbiosis is a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota.
• For example, a part of the human microbiota, such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void.

Causes

• Antibiotic or mold exposure
• Alcohol misuse
• Inappropriate diet
• Neonatal viral vinfections

Viral infections

In the first few years of life, colonization of the GI tract plays an indispensable role in shaping host immune development, regulation, and maintenance (63, 64). With age, the microbiome experiences decreasing plasticity and tolerance for new antigen exposure and environmental disruptions (63, 65). Following infancy, the microbiome seems to stabilize with relatively established communities that continue to shape mucosal and systemic immune homeostasis into adulthood (66). Thus, timing of environmental perturbations is likely an important factor for producing dysbiosis, which impacts disease susceptibility. The “Hygiene Hypothesis” proposes that exposure to antigens in early life during immune development can have profound effects for the development of autoimmune and allergic disease later on. Evidence suggests that instigating factors leading to T1D occur early in life – especially since a majority of early-onset individuals who progress to overt T1D before adolescence develop autoantibodies by 3 years of age (1, 67). However, most individuals are diagnosed with T1D in adulthood, hinting that tolerance for environmental stressors may not necessarily be limited to a defined age or that triggering events can occur long before disease onset (68).

Infections that are relatively mild later in life, may have the ability to be quite detrimental early in life at promoting T1D, as the immune system is not yet fully developed and may lack the ability to properly defend the host (69). Viruses cause dysbiosis (70–72), potentially signifying lasting consequences whereby individuals may develop a more autoimmune-skewed microbiome that might be characterized by decreased diversity and less beneficial bacteria (e.g., less butyrate producers). Studies in NOD mice have shown early life exposure to a “diabetogenic microbiome” through fecal microbiome transfers (FMT) can regulate B cell activation and promote T1D onset later on (69). However, when mice are given this same microbiome composition post-adolescence they do not experience the same modulation of the immune system and increased incidence of diabetes autoimmunity. Thus, there may be a unique window, particularly early in life, whereby disruptions in the microbiome from exogenous stressors like infection can have much larger implications on future health.

Miams

HCV

HBV

INFL

TMEV