Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits | Nature Communications

Bloodborne infections with Candida albicans are an increasingly
recognized complication of modern medicine. Here, we present a mouse
model of low-grade candidemia to determine the effect of disseminated
infection on cerebral function and relevant immune determinants. We show
that intravenous injection of 25,000 C. albicans cells causes a
highly localized cerebritis marked by the accumulation of activated
microglial and astroglial cells around yeast aggregates, forming
fungal-induced glial granulomas. Amyloid precursor protein accumulates
within the periphery of these granulomas, while cleaved amyloid beta
(Aβ) peptides accumulate around the yeast cells. CNS-localized C. albicans
further activate the transcription factor NF-κB and induce production
of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor (TNF), and Aβ
peptides enhance both phagocytic and antifungal activity from BV-2
cells. Mice infected with C. albicans display mild memory
impairment that resolves with fungal clearance. Our results warrant
additional studies to understand the effect of chronic cerebritis on
cognitive and immune function.

Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study. - PubMed - NCBI

 The molecules and pathways of the gut-brain axis represent new targets for developing methods to diagnose and treat psychiatric disorders. Manipulation of the gut microbiome with probiotics may be a therapeutic strategy with the potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species, can be imbalanced in the unhealthy human microbiome, and these fungal exposures were previously found elevated in schizophrenia. In a longitudinal, double-blind, placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we examined the impact of probiotic treatment on yeast antibody levels, and the relationship between treatment and antibody levels on bowel discomfort and psychiatric symptoms. We found that probiotic treatment significantly reduced C. albicans antibodies over the 14-week study period in males, but not in females. Antibody levels of S. cerevisiae were not altered in either treatment group. The highest levels of bowel discomfort over time occurred in C. albicans-seropositive males receiving the placebo. We observed trends towards improvement in positive psychiatric symptoms in males treated with probiotics who were seronegative for C. albicans. Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia. In conclusion, the administration of probiotics may help normalize C. albicans antibody levels and C. albicans-associated gut discomfort in many male individuals. Studies with larger sample sizes are warranted to address the role of probiotics in correcting C. albicans-associated psychiatric symptoms.



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Probiotic normalization of Candida albicans in schizophrenia: a randomized, placebo-controlled, longitudinal pilot study

The molecules and pathways of the gut-brain axis represent new targets for developing methods to diagnose and treat psychiatric disorders. Manipulation of the gut microbiome with probiotics may be a therapeutic strategy with the potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species, can be imbalanced in the unhealthy human microbiome, and these fungal exposures were previously found elevated in schizophrenia. In a longitudinal, double-blind, placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we examined the impact of probiotic treatment on yeast antibody levels, and the relationship between treatment and antibody levels on bowel discomfort and psychiatric symptoms. We found that probiotic treatment significantly reduced C. albicans antibodies over the 14-week study period in males, but not in females. Antibody levels of S. cerevisiae were not altered in either treatment group. The highest levels of bowel discomfort over time occurred in C. albicans-seropositive males receiving the placebo. We observed trends toward improvement in positive psychiatric symptoms in males treated with probiotics who were seronegative for C. albicans. Results from this pilot study hint at an association of C. albicans seropositivity with worse positive psychiatric symptoms, which was confirmed in a larger cohort of 384 males with schizophrenia. In conclusion, the administration of probiotics may help normalize C. albicans antibody levels and C. albicans-associated gut discomfort in many male individuals. Studies with larger sample sizes are warranted to address the role of probiotics in correcting C. albicans-associated psychiatric symptoms."



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Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder

Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut–brain mechanisms.



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Yeast infection linked to mental illness: Schizophrenia and bipolar disorder

In a study prompted in part by suggestions from people with mental illness, Johns Hopkins researchers found that a history of Candida yeast infections was more common in a group of men with schizophrenia or bipolar disorder than in those without these disorders, and that women with schizophrenia or bipolar disorder who tested positive for Candida performed worse on a standard memory test than women with schizophrenia or bipolar disorder who had no evidence of past infection."

Association between multiple sclerosis and Candida species: evidence from a case-control study.

This study reported associations between infection with a number of Candida species particularly C.Albicans  (odds ratio = 7.2 ) and multiple sclerosis, suggesting that yeast as well as viral species may be implicated in MS.

Candida species are the main cause of thrush

Innate immunity: One-two blow alerts immune system - Cell Signaling Update - Signaling Gateway

Innate immunity: Biphasic MAPK signaling discriminates between safe and dangerous forms of fungi.  Candida albicans