Bile can serve as a reservoir for funghi, making them harder to treat

[CrumblingCookie]

@Mauritio
Very nasty! Thanks for pointing me back to this thread.
One thing I was immediately wondering about is whether the less-lipophilic fluconazole would then be more potent against bile fungi than the significantly more lipophilic itraconazole, even though fluco is quite completely being excreted renally and itra biliary.
But the answer lay in your linked study: Fluco was shown to be useless in bile. Utterly.
There no mentioning of itra in this context. Only a remark, that fungi increase their itraconazole-resistance in the presence of cholesterol. However, this mechanisms affects all azoles. Essentially, candida and other fungi can salvage exogenous cholesterol to make up for loss of ergosterol synthesis and are thus less affected by the inhibiting impact of azoles.

So how to tackle these biliarly persisters?
I doubt they will only serve as a reservoir without already being harmful where they are. In your linked studies it says, C. albicans hyphenates upon contact with bile acids. I therefore assume they do bad things already in the liver and gallbladder and potentially alter the function of these organs or of the bile composition. @bearwithme

The water-soluble flucytosine is available as 500mg tablets (ANCOTIL) on prescription for specific systemic fungal infections... certainly nothing anyone would easily obtain officially from a doctor because of a hunch of biliary fungal persistence!
I had never heard of it before.
Side effects are kind of the usual; don't get pregnant or impregnate anyone else within 6 months, blood cell discorders, skin detachment, fatal hepatic lesions, hypokalemia and heart troubles, the whole cluster of confusion, headaches, vertigo, neuropathies, hallucinations as well as respiratory impairments or arrest and reduced kidney functions.
What do you peeps reckon - is it wortwhile to try out?

@Mauritio said in Bile can serve as a reservoir for funghi, making them harder to treat:

Im looking for anti-fungal candidates that fit the above category:

MSM
Small molecule and highly water soluble , fits the bill.

Any info on how methylsulfonylmethane would be antifungal?

Oregano oil or winter savory oil mostly for the carvacrol and thymol are again strongly lipophilic.

Berberine is strongly synergistic with azoles and can overcome azole-resistance.
Propolis extract is antifungal as well and can overcome azole-resistance.
Boron.
Balsamic turpentine may be mostly anti-biofilm.
Especially boron may be mostly preventative at regular low doses but tbh I'm really disappointed with all of these on their own not being anywhere near to being effective on their own.

Maybe a topical antifungal like nystatin or amphotericin B for the GI lumen over quite a long term, plus a combination of systemic substances: boron, berberine, propolis extract, + pharmaceutical antifungal?

[CrumblingCookie]

@Mauritio said in Boron supplements:

@CrumblingCookie I agree with you on subclinical fungal infections.
They're very hard to get rid of. I posted a study about fungi hiding in the gallbladder when attacked. Let that sink in.

It's just as bad when we look into CNS persistence of fungal infections in chronic brain disorders, Alzheimers and dementia:
Tulane University & Tulane National primate research center, 2022

The potential contribution of pathogenic microbes to dementia-inducing disease is a subject of considerable importance. Alzheimer’s disease (AD) is a neurocognitive disease that slowly destroys brain function, leading to cognitive decline and behavioral and psychiatric disorders. The histopathology of AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide in the form of parenchymal plaques and abnormal aggregated tau protein in the form of neurofibrillary tangles.

Observational, epidemiological, experimental, and pathological studies have generated evidence for the complexity and possible polymicrobial causality in dementia-inducing diseases. The AD pathogen hypothesis states that pathogens and microbes act as triggers, interacting with genetic factors to initiate the accumulation of Aβ, hyperphosphorylated tau protein (p-tau), and inflammation in the brain. Evidence indicates that Borrelia sp., HSV-1, VZV (HHV-2), HHV-6/7, oral pathogens, Chlamydophila pneumoniae, and Candida albicans can infect the central nervous system (CNS), evade the immune system, and consequently prevail in the AD brain. Researchers have made significant progress in understanding the multifactorial and overlapping factors that are thought to take part in the etiopathogenesis of dementia; however , the cause of AD remains unclear .

“It has been suggested that Aβ functions as an antimicrobial peptide. Interestingly, C. albicans was found to be sensitive to synthetic Aβ and brain homogenates from AD patients that were capable of inhibiting fungal growth [178]. Additionally, it was demonstrated that Aβ protects against C. albicans in glial cells as well as invivo in nematodes [179]. ”

“Alonso and colleagues provided extensive evidence that disseminated mycoses are potential causative agents or risk factors for AD [173,180]. Different fungal genera detected in AD brain tissue include Malassezia, Fusarium, Candida, Cladosporium, Alternaria, and Botrytis [181]. An analysis of CSF revealed significant levels of Candida albicans and Candida glabrata in samples from AD patients. Approximately >89.6% of serum from AD patients tested positive for antibodies to Candida compared to 8.8% for controls [173].”

“The different species that were detected included Saccharomyces cerevisiae, Malassezia globosa, Malassezia restricta, and Penicillium. Furthermore, this group detected yeast and fungal proteins, including (1,3)-β-glucan, fungal polysaccharides, and mycoses, in the peripheral blood of AD patients, which suggests that a chronic fungal infection may increase the risk of dementia [173,180]. More strikingly, yeast-like cells and hyphal structures were observed in CNS tissue from AD patients using polyclonal antibodies against a variety of fungi [181].

Pisa et al. also provided strong evidence for fungal infection in AD patients [170]. Brain sections derived from AD patients showed that all were infected with fungi [170]. Fungal material was detected intra- and extracellularly in the neurons of tissues of AD patients, but no fungal material was observed in tissue from control individuals [170]. Moreover , fungal DNA and proteins were also found in brain regions including the frontal cortex, hippocampus, cerebellar hemisphere, and choroid plexus but not in control patient tissue. ”

[sunsunsun]

idk about in context of bile, but iron chelation in fungi via doxycycline makes fluconazole anti fungal against some candida rather than just fungistatic or no effect. aspirin is also an iron chelator.