Chronic Stress [ SNS Hyperactivity ] + High Cortisol [ Hypercortisolism ]

 

Various studies indicate that although short-term stress may increase sIgA levels, chronic or prolonged stress leads to a decrease in sIgA production. This suppression is associated with persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in elevated cortisol levels. High cortisol can inhibit the secretion and transport of sIgA across mucosal surfaces, weakening the first line of the GI immune defense. [14][15].

 

Another study demonstrated that chronic stress caused sIGA declines whilst experiencing the stress, but also that the sIGA levels remained low for 6 days after the stress was alleviated. [16] 

 

Chronic Infections 

 

• SIBO

• Candidasis

• Dysbiosis

• Helminth Infection

• Protozoa Infection

 

Chronic gastrointestinal infections create a state of persistent immune system activation, which has a direct impact on levels of secretory IgA (sIgA), the gut’s frontline antibody for mucosal defense. 

 

Under normal conditions, sIgA forms a protective coating along the intestinal lining, preventing pathogens from attaching, neutralizing toxins, and supporting a healthy microbial balance.

When infections become long-standing, however, several interconnected mechanisms reduce the body’s ability to maintain adequate sIgA, including:

 

Resource diversion: Continuous inflammation forces the immune system to prioritize pro-inflammatory pathways, leaving fewer resources available for the specialized process of IgA production.
 

Impaired B-cell signaling: Normally, B cells undergo ‘class switching’ to become IgA-producing plasma cells. Chronic immune stress disrupts this signaling, limiting the conversion to IgA-producing cells.
 

Excessive demand: Persistent infections create a constant need for sIgA. Over time, this demand outpaces the body’s ability to produce and secrete sufficient antibody levels.
 

Cytokine imbalance: Pro-inflammatory cytokines, such as TNF-α and IL-6  dominate in chronic infections. These suppress the anti-inflammatory cytokines like IL-10, that are essential for promoting IgA class switching.
 

The combined effect is a gradual depletion of sIgA, leaving the mucosal barrier weakened. This increases susceptibility to further microbial overgrowth, recurrent infections, dysbiosis, and ongoing cycles of inflammation. Over time, this vicious cycle contributes not only to local gut dysfunction but also to chronic states of GI dysfunction or disease. [17][18][19][20]

 

Low Mucus Production 

 

The mucus gel layer covering the gastrointestinal tract is an important component of the gut-associated lymphoid tissue (GALT) as it is home to sIGA, as well as home to the bacteria necessary to produce beneficial short-chain fatty acids (SCFAs) through fermentation.

 

Subsequently poor mucus production or mucus layer degradation limits housing availability. The resulting reduction of SCFAs causes GI immune impairments and dysfunctions because SCFAs initiate signaling pathways that influence immune cell function, enhance mucosal immunity and support the development of Treg cells. The reduction of sIGA limits the guts main antibody from performing its work to clear pathogenic organisms. [10][11][12][13]

 

Antibiotics

 

Antibiotic treatments can affect the development of important immune structures such as the Peyer’s patches. These patches are crucial for the immune system to function properly. Antibiotics can also reduce the number of immune cells in the gut, which leads to a long-term decrease in the formation of germinal centers, which are areas where immune cells are activated. Antibiotics have also been associated with a reduction in the production of IgA. [21][22]

 

High Fat, Low Fibre Diets

 

Clinical studies have demonstrated that GALT is sensitive to the changes in the dietary composition. With high fat contributing to the destruction of T cells in the GALT. Whereas high fibre has been associated with increased T-cell immune responses and macrophage activity in the gut.It also promotes a greater number of M cells. [23][24]

 

Nutrient Deficiency 

 

Specific vitamins and amino acids play integral roles in the GALT. Deficiencies in the following have a negative impact on the GALT system.

 

• Vitamin A

• Vitamin D

• Threonine