I became interested in H. Pylori after reading about a patient whose PSSD resolved after he was treated for his H. Pylori infection. H. Pylori is a very common infection, with some experts suggesting that over half of the world (most in developing nations) might have this pesky bacteria. Most people will never exhibit any signs of infection, but H. Pylori can wreck havoc in the background. For example, H. Pylori is suspected to be a contributing factor to many GI tract cancers. In addition, around 10-15% of people with H. Pylori will develop ulcers.
Why am I interested for PSSD?
There are a few reasons. First of all, Helicobacter pylori is associated with lower androgen activity among men. More importantly, the connection between sexual dysfunction and H. Pylori is documented in the literature. A 2016 study from Nasrat et al. shows that the infection increased mucosal production of inflammatory cytokines which could play an integral role in the pathogenesis of ED. In their study, 17 of young participants with erectile Dysfunction (ED) and H. Pylori infection were treated with antibiotics. After H. Pylori was resolved, 90% of them returned to their normal erectile functioning. Finally, there have been online reports of deadened libido during H. Pylori infection that alleviate after treatment.
The PSSD research effort is rarely fruitful. Because we are working with barely any budget and only a few hundred active members, it’s hard to get new ideas. Because of this, tracking down those that are plausible is a good use of time. At this point, it’s impossible to say if H. Pylori has any connection to PSSD at all, but it is possible. At the very least this work will acquaint us with the world of inflammatory cytokines and their possible role in PSSD pathology.
As such, onwards to today’s paper!
The researchers are interested in the connection between the Central Nervous System (The brain and spinal cord), and the Enteric Nervous System (which consists of some 500 million neurons – note that this is A LOT of neurons for a region that we rarely think of as neurological. It’s 1/200 as many as your brain and 5 times the number of neurons in your spinal cord!). This “little brain” communicates with your brain via endocrine, immunological and neuronal messages. The researchers claim that this communication is bidirectional.
They note that stress and mental disorders have a harmful effect on digestive tract function and intestinal bacterial flora, and that patients with digestive tract disorders have a high prevalence of co-morbid mental disorders (depression/anxiety/OCD). It seems as if H. Pylori could impact these communications between neural areas. Their arguments and cited sources are below (take special note of #4):
(1) the overlapping of upper and lower digestive tract functional symptoms in H. pylori infected patients[18,41–43] and the effect of H. pylori infection on IBS symptoms[43] (but see Breckan et al[44]) and pancreatic juice secretion[45]
(2) the protection against IBD appearance by H. pylori infection[17,46] resulting from changes induced in brain-gut axis function (neuroendocrine-immune crosstalk)[6,15,21,22,26,47,48]
(3) the association of H. pylori infection with ANS-related extra-digestive diseases, such as atherosclerosis or cardiac arrhythmia[3,35]
(4) the improved physical and psychological health-related quality of life and sexual relationships after digestive tract symptom alleviation and H. pylori eradication[49,50]
(5) the proposed association between H. pylori infection and the development of axonal type Guillain-Barré neuropathy, multiple sclerosis and epilepsy[51–53], and case reports of gastric MALT lymphoma followed by primary CNS lymphoma[54]; and
(6) the modulation of ANS (Autonomic Nervous System) balance by H. pylori infection[35].
…
[H. Pylori influence] the release of various neurotransmitters, including acetylocholine (vagal nerve, parasympathetic part), noradrenaline, adrenaline and sympathetic dopamine, as well as the neuropeptides leptin, ghrelin, calcitonin gene-related peptide (CGRP), nitric oxide, neuropeptide Y, substance P (SP), somatostatin (STS) and cholecystokinin (CCK).
Moreover, H. pylori infection is associated with the up-regulation of toll-like receptors and cytokine overproduction, especially tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, and IL-8[57–59], thereby indirectly influencing the brain-gut axis. These immune-mediators may stimulate mast cells (MC) in the gastric mucosa, as well as the hypothalamus and brain stem (via neuroendocrine-immuno crosstalk)[6,22], thereby activating the sympathetic ANS and pituitary-suprarenal axis, resulting in increased cortisol and adrenalin secretion[6,21,22,60,61].
What could this mean for sufferers of H. Pylori?
(1) axon injury or stimulation (neuroinflammation) by bacterial cytotoxins (VacA)[60,72,78], neutrophil-attractant chemokine IL-8[79], and/or neutrophil-activating protein (H. pylori-NAP)[75,79]
(2) axon damage or stimulation by autoimmunological reactions due to mimicry of VacA, bacterial aquaporin (AQP), H. pylori-NAP and human antigens[51,53,79,80]
(3) H. pylori-induced production of free radicals[80–82], cytotoxins and cytokines[57–61,78], which may also result in blood-brain barrier disruption
(4) changes in neurotransmitter secretion in gastric mucosa and spinal cord[56,72,75,81,83–85]
(5) neuron injury resulting from gastric mucosa atrophy and a decrease in vitamin B12 absorption[86]
A combination of these effects could cause problems for PSSD sufferers, especially anything that increased inflammatory cytokine formation or increased sympathetic nervous system activity or neurotransmitter function. The researchers go on (Note number 2)…
Intermediate effects of chronic H. pylori infection on brain-gut axis function have been clinically observed as:
(1) the alteration of feeding patterns[15,19]
(2) cognitive and memory dysfunction[18,19,27,82,93], increased vulnerability to stress[15,19,27] and anxiety- and depressive-like behaviors[19]
(3) alterations in endocrine functions of the stomach, including the production of SP, VIP, CCK, STS, gastrin and ghrelin[81,94]
(4) changes in visceral ANS balance and the action of vagal visceral reflexes[95]
(5) alterations in gastrointestinal motility[21]
(6) increased visceral perception (chemo- and mechano-hypersensitivity)[67,96]
(7) changes in gastrointestinal secretion[21,45]
(8) increased intestinal permeability[23,61]
(9) intestinal microbiota[87–89], with indirect effects on the brain-gut axis[27,28,97–99]
(10) alterations in immunological reactivity, resulting in decreased prevalence of food allergies and inflammatory bowel diseases[46,100]
(11) the overlapping of gastrointestinal disorders from upper and lower parts of the digestive tract[43].
Moreover, H. pylori eradication has also been shown to normalize some of these alterations[55,95,100–103].
…
A proportion of H. pylori effects on the brain-gut axis may be secondary to central and peripheral nerve demyelination and blood-brain barrier disruption[79]. The cross-mimicry between VacA and H. pylori-NAP is recognized as the most important immunological reaction[79], which induces auto-reactive T cells and initiates or worsens gastric autoimmunity leading to atrophic gastritis and gastric cancer[91,92].
As noted above, H. Pylori is implicated in memory functioning:
In a large, cross-sectional study of United States adults by Beydoun et al[115], H. pylori-seropositivity was associated with poor cognition based on declining verbal memory test performance. H. pylori, as with other urease-positive bacteria that produce ammonia, is also recognized as a cause of liver-like encephalopathy[116]. In a study by Roubaud Baudron et al[117] who followed-up individuals aged 65 years or older for 20 years, H. pylori infection was recognized as a significant risk factor for the development of dementia as a result of enhanced neurodegenerative processes, a hypothesis that has been suggested by Deretzi et al[80].
What might these findings mean?
First of all, we have no idea if anyone with PSSD has H. Pylori infection. That’s step one. I’ve ordered my tests, and will be completing them soon.
Is there an high chance that H. Pylori contributes to the PSSD symptoms of most sufferers?
I would say no, but with a lack of existing therapies and because of the possible sexual, mental, and emotional side effects of H. Pylori, more research and testing is necessary. In the end, there is only one way to know: test.
Ghost
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