Candida albicans is abundant in the human gut mycobiota but this species does not colonize the mouse gastrointestinal tract. C. albicans administration in dextran-sulfate solution (DSS) inducedcolitis mouse model (DSS+Candida) might resemble more to human condition, therefore, a DSS colitis model with Candida administration was studied; first, to test the influence of fungi in DSS model and second, to test the efficacy of Lactobacillus rhamnosus L34. We demonstrated serum (1→3)-β-D-glucan (BG) elevation in patients with IBD and endoscopic moderate colitis in clinical remission, supporting the possible influence of gut fungi toward IBD in human. Then, in mouse model, Candida gavage was found to worsen the DSS model indicated by higher mortality rate, more severe colon histology and enhanced gut-leakage (FITC-dextran assay, endotoxemia, serum BG and blood bacterial burdens) but did not affect weight loss and diarrhea. DSS+Candida induced higher pro-inflammatory cytokines both in blood and in intestinal tissue. Worsened systemic pro-inflammatory cytokine responses in DSS+Candida compared with DSS alone was possibly due to the more severe translocation of LPS, BG and bacteria (not fungemia) from gut into systemic circulation. Interestingly, bacteremia from Pseudomonas aeruginosa was more frequently isolated from DSS+Candida than DSS alone. In parallel, P. aeruginosa was also isolated from fecal culture in most of the mice in DSS+Candida group supported by prominent Gammaproteobacteria in fecal microbioata analysis. However, L. rhamnosus L34 attenuated both DSS+Candida and DSS model through the attenuation of gut local inflammation (cytokines and histology), gut-leakage severity, fecal dysbiosis (culture method and microbiome analysis) and systemic inflammation (serum cytokines). In conclusion, gut Candida in DSS model induced fecal bacterial dysbiosis and enhanced leaky-gut induced bacteremia. Probiotic treatment strategy aiming to reduce gut-fungi and fecal dysbiosis could attenuate disease severity. Investigation on gut fungi in patients with IBD is highly interesting.
The influence of gut-leakage or gut-microbiota upon lupus progression was explored in 2 lupus mouse models. Pristane, administered in 4-wk-old wild-type (WT) female mice, induced lupus characteristics at 24-wk-old similar to the lupus-onset in FcGRIIb−/− mice. Gut-microbiota alteration was induced by co-housing together with the gavage of feces from 40-wk-old FcGRIIb−/− mice (symptomatic lupus). On the other hand, gut-leakage was induced by dextran sulfate solution (DSS). DSS and gutmicrobiota alteration induced high serum anti-dsDNA immunoglobulin (Ig) as early as 30 days post-DSS only in FcGRIIb−/− mice. DSS, but not gut-microbiota alteration, enhanced lupus characteristics (serum creatinine and proteinuria) in both lupus models (but not in WT) at 60 days post-DSS. Indeed, DSS induced the translocation of molecular components of gut-pathogens as determined by bacterial burdens in mesenteric lymph node (MLN), endotoxemia (gut-bacterial molecule) and serum (1→3)-β-Dglucan (BG) (gut-fungal molecule) as early as 15 days post-DSS together with enhanced MLN apoptosis in both WT and lupus mice. However, DSS induced spleen apoptosis in FcGRIIb−/− and Wt mice at 30 and 60 days post-DSS, respectively, suggesting the higher impact of gut-leakage against spleen of lupus mice. In addition, macrophages preconditioning with LPS plus BG were susceptible to starvationinduced apoptosis, predominantly in FcGRIIb−/− cell, implying the influence of gut-leakage upon cell stress. in summary, gut-leakage induced gut-translocation of organismal-molecules then enhanced the susceptibility of stress-induced apoptosis, predominantly in lupus. Subsequently, the higher burdens of apoptosis in lupus mice increased anti-dsDNA Ig and worsen lupus severity through immune complex deposition. Hence, therapeutic strategies addressing gut-leakage in lupus are interesting.Systemic lupus erythematosus (SLE) is a common autoimmune disease with multi-organ involvement 1 . Fc gamma receptor IIb (FcGRIIb) dysfunction polymorphism associates with SLE, particularly in Asian populations 2 , possibly due to malaria-based selection pressure 3 . Indeed, the overexpression of FcGRIIb, either in autoimmune-prone mouse strains or wild-type (WT) animals, heightened the threshold for induction of autoimmune disease 4 . The defects of FcGRIIb, the only inhibitory receptor in FcGR family, induce exaggerated immune responses and cause lupus 5 . As such, FcGRIIb−/− mouse is an established lupus mouse model with lupus characteristics as early as 20-24 wks old and develops full-blown lupus after 32-40 wks old 5,6 . In parallel, a single peritoneal injection creatinine index (UPCI; detail later) and serum anti-dsDNA immunoglobulin (Ig) before the further experiments. Symptomatic lupus was defined as increased serum anti-dsDNA Ig together with high level of UPCI and/ or serum Cr in comparison with age-matched control WT mice.Dextran sulfate solution (DSS) induced gut-leakage and co-housing with fecal gavage for gut microbiota alteration. Dextran sulfate solution (DSS) (Sigm...
alleles from Thai population with HLA alleles from both European and Asian countries, the distribution landscape of HLA-associated drug hypersensitivity across many countries could be observed. Consequently, this pharmacogenetics database offers a comprehensive view of pharmacogenetics marker distribution in Thailand that could be used as a reference for other Southeast Asian countries to validate the feasibility of their future pharmacogenetics deployment.
The influence of gut fungi in chronic colitis was investigated by repeated oral administration of Candida albicans in a 3% dextran sulfate solution (DSS) induced-colitis mouse model. Candida administration in the DSS (DSS+Candida) model enhanced the mortality rate and induced bacteremia (without candidemia) resulting from a gut perm-selectivity defect despite similar diarrheal severity in mice treated with DSS alone. The dominant fecal bacteria in DSS+Candida and DSS alone mice were Pseudomonas spp. and Enterobacter spp., respectively, implying that Candida induced gut dysbiosis. Interestingly, chloramphenicol-resistant bacterial colonies, predominantly Pseudomonas spp., appeared in the feces and blood of DSS+Candida mice (not the DSS alone group) during fungal culture. These antibiotic-resistant bacteria were also isolated, ex vivo, by incubating mouse feces with DSS and heat-killed Candida or (1→3)-β-D-glucan, suggesting bacterial fermentation on fungi. Administration of Pseudomonas aeruginosa isolated from chloramphenicol-resistant bacteria in the DSS+Candida model enhanced the severity of disease, and increased growth of isolated P aeruginosa in blood agar containing heat-killed Candida was demonstrated. These data suggested the selection of a highly virulent bacterial strain following fecal Candida presentation in the gut. Additionally, reduction of fecal fungi with fluconazole decreased the burden of chloramphenicol-resistant bacteria, attenuating the severity of DSS+Candida. In conclusion, gut Candida induced bacteremia in the DSS model through an inflammation-induced gut perm-selectivity defect and facilitated the growth of some gut bacteria. Treatment strategies aimed at reducing gut fungi could attenuate disease severity. Further investigation of gut fungi in inflammatory bowel disease is warranted.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.