Uremia-Induced Gut Barrier Defect in 5/6 Nephrectomized Mice Is Worsened by Administration through a Synergy of Uremic Toxin, Lipopolysaccharide, and (1➔3)-β-D-Glucan, but Is Attenuated by L34.

A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-β-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and L34 (L34) on CKD were investigated using oral -administered 5/6 nephrectomy (5/6Nx) mice.

Lactobacillus rhamnosus attenuates Thai chili extracts induced gut inflammation and dysbiosis despite capsaicin bactericidal effect against the probiotics, a possible toxicity of high dose capsaicin.

Because of a possible impact of capsaicin in the high concentrations on enterocyte injury (cytotoxicity) and bactericidal activity on probiotics, Lactobacillus rhamnosus L34 (L34) and Lactobacillus rhamnosus GG (LGG), the probiotics derived from Thai and Caucasian population, respectively, were tested in the chili-extract administered C57BL/6 mice and in vitro experiments. In comparison with placebo, 2 weeks administration of the extract from Thai chili in mice caused loose feces and induced intestinal permeability defect as indicated by FITC-dextran assay and the reduction in tight junction molecules (occludin and zona occludens-1) using fluorescent staining and gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the chili extracts also induced the translocation of gut pathogen molecules; lipopolysaccharide (LPS) and (1→3)-β-d-glucan (BG) and fecal dysbiosis (microbiome analysis), including reduced Firmicutes, increased Bacteroides, and enhanced total Gram-negative bacteria in feces.

Increased susceptibility to dextran sulfate-induced mucositis of iron-overload β-thalassemia mice, another endogenous cause of septicemia in thalassemia.

Enterocyte damage and gut dysbiosis are caused by iron-overload in thalassemia (Thl), possibly making the gut vulnerable to additional injury. Hence, iron-overload in the heterozygous β-globin deficient (Hbbth3/+) mice were tested with 3% dextran sulfate solution (DSS). With 4 months of iron-gavage, iron accumulation, gut-leakage (fluorescein isothiocyanate dextran (FITC-dextran), endotoxemia, and tight junction injury) in Thl mice were more prominent than WT mice.

Gut leakage enhances sepsis susceptibility in iron-overloaded β-thalassemia mice through macrophage hyperinflammatory responses.

Iron overload induces intestinal-permeability defect (gut leakage), and gut translocation of organismal molecules might enhance systemic inflammation and sepsis severity in patients with thalassemia (Thal). Hence, iron administration in Hbb mice, heterozygous β-globin-deficient Thal mice, was explored. Oral iron administration induced more severe secondary hemochromatosis and gut leakage in Thal mice compared with wild-type (WT) mice.

Leaky-gut enhanced lupus progression in the Fc gamma receptor-IIb deficient and pristane-induced mouse models of lupus.

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).

Additional administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by L34.

is abundant in the human gut mycobiota but this species does not colonize the mouse gastrointestinal tract. administration in dextran-sulfate solution (DSS) induced-colitis mouse model (DSS+) might resemble more to human condition, therefore, a DSS colitis model with administration was studied; first, to test the influence of fungi in DSS model and second, to test the efficacy of 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.

Administration of Candida Albicans to Dextran Sulfate Solution Treated Mice Causes Intestinal Dysbiosis, Emergence and Dissemination of Intestinal Pseudomonas Aeruginosa and Lethal Sepsis.

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.