The pathophysiology of Painful Bladder Syndrome / Interstitial Cystitis is currently unknown. Histamine seems to play a major role in IC as neurogenic inflammation is one of the hypothesis of IC. Antihistamines are part of the guideline recommendations, foods high in histamine (e.g. Shorter-Moldwin Food Sensitivity Questionnaire) aggravate IC symptoms. Vaginal microbiome tests recently assume changes in IC patients. Within this retrospective case collection the role of histamine overload in the gut is highlighted along with a gut and vaginal microbiota analysis.

Between September 2012 and January 2018 a total of 97 women (range 19 to 81 years, mean age 47) were surveyed. Histamine in fecal samples was measured with a commercially available ELISA kit (LDN Labor Diagnostika Nord GmbH & Co. KG, Nordhorn, Germany).The results were compared to an age-matched cohort of 57 healthy women. Additionally, vaginal swabs were analysed. Furthermore a complete gut microbiota analysis was done in all women.

Stool results: 
In 63 of the 97 analysed women elevated histamine levels were found in fecal samples. The first 57 IC patients  were compared to an age-matched control-group of 57 healthy women for test validation. Moreover in most of the patients the protective anaerobic indicator microbiota (mainly lactobacilli and bifidobacteria) was also diminished.
Vaginal swab results:
In 44 out of the 63 women with the elevated histamine level the presence of Enterococcus ssp. and / or Enterobacteriaceae in vaginal swabs was also detected. In 27 women only the presence of Enterococcus ssp. and / or Enterobacteriaceae was found. 
Only 7 women did neither show elevated histamine levels nor the presence of Enterococcus ssp. and/or Enterobacteriaceae in vaginal swabs.

There are paralleles between IC and histamine intolerance: prevalence of 1%, female predominance, middle age, symptom improvement in pregnancy due to a 500 fold higher level of the diamine oxidase (histamine eliminating enzyme). Histamine intolerance is a poorly described disease which can present with a variety of symptoms like e.g. migraine, irritable bowel syndrome, urticaria, tachykardia, nasal congestion and perhaps also IC? Histamine can increase intestinal permeability causing a leaky gut which prompts the body to initiate immune reactions like autoimmune diseases or leads to pain through toll-like receptor (TLR)-4 inflammatory response (shown by the MAPP research group). Both irritable bowel syndrome and autoimmune diseases are comorbidities of IC. Recent data in rats assume a cross-sensitization between bladder and colon due to altered permeability in 1 organ which affects the other organ.
The role of the vaginal dysbiosis with predominance of Enterococcus ssp. and/ or Enterobacteriaceae in the context of urogenital pain remains unclear as there are no data existing so far. Recent vaginal microbiome analyses suggest changes in IC patients.

Testing for histamine in stool and vaginal dysbiosis could be new diagnostic tools in Painful Bladder Syndrome / Interstitial Cystitis patients. Treatment with pre- and probiotics and colon cleansing already known in alternative medicine could be a new therapeutic option for IC patients.

Schrepf et al, Pain 2014 Sep; 155(9):1755-61
Greenwood-Van Meerveld et al, J Urol 2015;194:804-11
Brandmeier-Fleming et al, Sci Rep 2016; 6:26083