Lactobacillus acidophilus KBL409 Reduces Kidney Fibrosis via Immune Modulatory Effects in Mice with Chronic Kidney Disease.

SCOPE: Intestinal dysbiosis has been reported to play an important role in the pathogenesis of various diseases, including chronic kidney disease (CKD). Here, to evaluate whether probiotic supplements can have protective effects against kidney injury in an animal model of CKD is aimed. METHODS AND RESULTS: An animal model of CKD is established by feeding C57BL/6 mice a diet containing 0.2% adenine. These model mice are administered Lactobacillus acidophilus KBL409 daily for 4 weeks. Features of adenine-induce CKD (Ade-CKD) mice, such as prominent kidney fibrosis and higher levels of serum creatinine and albuminuria are improved by administration of KBL409. Ade-CKD mice also exhibit a disrupted intestinal barrier and elevate levels of TNF-α, IL-6, and 8-hydroxy-2'-deoxyguanosine. These changes are attenuated by KBL409. Administration of KBL409 significantly reduces macrophage infiltration and promotes a switch to the M2 macrophage phenotype and increasing regulatory T cells. Notably, the NLRP3 inflammasome pathway is activated in the kidneys of Ade-CKD and decreases by KBL409. In primary kidney tubular epithelial cells treated with p-cresyl sulfate, short-chain fatty acids significantly increase M2 macrophage polarization factors and decrease profibrotic markers. CONCLUSIONS: These results demonstrate that supplementation with the probiotic KBL409 has beneficial immunomodulating effects and protects against kidney injury.

Improvement in host metabolic homeostasis and alteration in gut microbiota in mice on the high-fat diet: A comparison of calcium supplements.

Despite the previously reported health benefits of calcium intake for the attenuation of metabolic disease, few studies have investigated the relationships among calcium intake, gut microbiota, and host metabolism. In this study, we assessed the effects of calcium supplementation on host microbial community composition and metabolic homeostasis. Mice were fed a high-fat diet with different calcium concentrations (4 and 12 g/kg) of 2 calcium supplements, calcium carbonate and calcium citrate. Supplementation with the higher concentration of calcium citrate significantly prevented body weight gain and decreased plasma biomarkers for metabolic disorder compared to calcium carbonate supplementation. Both calcium supplementation led to changes in microbial composition, increased propionate production and increased anorexigenic GLP-1 gene expression. The calcium citrate groups also experienced less metabolic endotoxemia. Our findings suggested that calcium supplementation could ameliorate host metabolic disorder caused by a high-fat diet, due to gut microbiota changes as well as decreased intestinal inflammation.

Faecalibacillus intestinalis gen. nov., sp. nov. and Faecalibacillus faecis sp. nov., isolated from human faeces.

Two long-rod-shaped, Gram-stain-positive, obligately anaerobic and non-spore-forming strains, SNUG30099T and SNUG30370T, were isolated from faecal samples of healthy Korean subjects. The strains formed circular ivory-coloured colonies on Brain-heart infusion medium supplemented with 0.5% Difco yeast extract (YBHI) agar and cells were approximately 3.5-4.5×0.3-0.4 µm in size. Taxonomic analyses based on 16S rRNA gene sequences distinguished the strains from other species within the family Erysipelotrichaceae. The closest relative of strains SNUG30099T and SNUG30370T was Longibaculum muris (92.9 % and 93.6 % similarity, respectively), followed by Clostridium saccharogumia (92.3 % and 92.2 %). Phylogenetic inference also divided the strains into a unique branch that differed from other related strains that belong to the family Erysipelotrichaceae. DNA G+C contents based on the whole genome sequences of strains SNUG30099T and SNUG30370T were 29.2 and 30.2 mol%, respectively. Both novel strains possessed meso-diaminopimelic acid as the peptidoglycan, and phosphatidylethanolamine was observed as one of the major polar lipids. The major cellular fatty acid composition was different from those of other related taxa. In addition, the profile of biochemical activities advocated that the strains have distinct characteristics in comparison to other strains. Taken together, a novel genus, named Faecalibacillus gen. nov., is proposed, which includes the type species Faecalibacillus intestinalis sp. nov. for strain SNUG30099T and Faecalibacillus faecis sp. nov. for strain SNUG30370T. The type strains of these novel species are SNUG30099T (=KCTC 15631T=JCM 32256T) and SNUG30370T (=KCTC 15632T=JCM 32257T).

Inactivation of influenza A virus via exposure to silver nanoparticle-decorated silica hybrid composites.

Influenza A virus (IFV-A) is one of the main cause of seasonal flu and can infect various of host species via the reassortment of segmented RNA genomes. Silver nanoparticles (AgNPs) have been known as excellent antiviral agent against IFV. However, the use of free AgNPs has several major drawbacks, including the inherent aggregation among AgNPs and unwanted cytotoxic or genotoxic damages for human body via inhalation or ingestion. In this study, we assessed the efficacy of our novel ~ 30-nm-diameter AgNP-decorated silica hybrid composite (Ag30-SiO2; ~ 400 nm in diameter) for IFV-A inactivation. Ag30-SiO2 particles can inhibit IFV-A effectively in a clear dose-dependent manner. However, when real-time RT-PCR assay was used, merely 0.5-log10 reduction of IFV-A was observed at both 5 and 20 °C. Moreover, even after 1 h of exposure to Ag30-SiO2 particles, more than 80% of hemagglutinin (HA) damage and 20% of neuraminidase (NA) activities had occurred, and the infection of Madin-Darby Canine Kidney (MDCK) cells by IFV-A was reduced. The results suggested that the major antiviral mechanism of Ag30-SiO2 particles is the interaction with viral components located at the membrane. Therefore, Ag30-SiO2 particles can cause nonspecific damage to various IFV-A components and be used as an effective method for inactivating IFV-A.

New perspectives regarding the antiviral effect of vitamin A on norovirus using modulation of gut microbiota.

Gut microbiota has been revealed to play an important role in various health conditions, and recent studies have suggested the modulation of gut microbiota as a therapeutic strategy. There is no effective treatment of norovirus infection, though vitamin A has been suggested to have an antiviral effect in an epidemiological study. We demonstrated that vitamin A significantly inhibited murine norovirus replication. Vitamin A supplementation significantly increased the abundance of Lactobacillus sp. during norovirus infection, which played a crucial role in antiviral efficacy, inhibiting murine norovirus. Therefore, we elaborated the antiviral effect of vitamin A via modulation of gut microbiota. Furthermore, we suggest a novel strategy, using potential probiotics, as having a protective and therapeutic effect on noroviral infection.

Vitamin A modifies the intestinal chemokine and cytokine responses to norovirus infection in Mexican children.

Vitamin A supplementation is associated with divergent clinical norovirus (NoV) outcomes in Mexican children. Fecal cytokine concentrations following NoV genogroup infections among 127 Mexican children 5-15 mo old enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were determined to clarify the role the gut immune response plays in these associations. Stools collected from supplemented children [20,000 IU retinol (3.3 IU = 1 µg retinol) for children < 12 mo of age; 45,000 iu for children ≥ 12 mo] or children in the placebo group were screened for NoV genogroups I (GI) and II (GII). Monocyte chemoattractant protein-1 (MCP-1), TNFα, IL-5, IL-6, IL-8, IL-4, IFNγ, and IL-10 fecal concentrations were also determined. Differences in cytokine levels between the 2 groups following GI and GII infections were determined using ordered logistic regression models. MCP-1 and IL-8 levels were greater among GI- and GII-infected children, respectively, compared with uninfected children, whereas IL-5 levels were greater following both genogroup infections. MCP-1, IL-8, and IL-6 fecal levels were reduced among supplemented children with GII-associated diarrhea compared with the placebo group. Vitamin A-supplemented, GII-infected children had reduced MCP-1 and TNFα levels compared with GII-infected children in the placebo group (P-interaction = 0.02 and 0.03, respectively). Supplemented children with GI-associated diarrhea had higher TNFα and IL-4 levels compared with children in the placebo group with diarrhea (P-interaction = 0.02 and 0.02, respectively). The divergent effects of supplementation on NoV outcomes may result from the different effects vitamin A has on the genogroup-specific immune responses.

High diversity and abundance of antibiotic-resistant Escherichia coli isolated from humans and farm animal hosts in Jeonnam Province, South Korea.

The spread of antibiotics resistance among bacteria is a threat to human health. Since South Korea uses approximately 1.5 times more antibiotics than do other OECD countries, this is likely to impact the numbers and types of antibiotic-resistant bacteria found in the environment. In this study we examined feces from domesticated animals and humans for the diversity and abundance of antibiotic-resistant Escherichia coli. Abundant antibiotic-resistant E. coli were isolated from all the tested animals and humans and were examined by horizontal, fluorophore-enhanced, rep-PCR (HFERP) DNA fingerprint analysis. A total of 793 unique, non-clonal, E. coli isolates were obtained from the 513 human and animal hosts examined. Antibiotic resistance analysis, done using 14 antibiotics, indicated that 72.3% of the isolates (573 of 793) were found resistant to more than one antibiotic. The E. coli isolated from swine were resistant to the greatest number of antibiotics. Tetracycline resistant E. coli were routinely isolated from all animal hosts (36 to 77% per host), except for dairy cattle (9.3%). Twenty nine E. coli isolates from all hosts, except for duck, were resistant to more than 10 antibiotics. Gene transfer and southern hybridization studies revealed that resistance to 13 of the antibiotics was self-transmissible, and likely mediated by plasmids and integrons. Since genetically diverse and numerically abundant antibiotic-resistant E. coli were consistently recovered from chicken, swine and other domesticated animals in South Korea, our results suggest that the use of sub-therapeutic levels of antibiotics for disease prophylaxis and growth promotion should be curtailed.

Vitamin A supplementation has divergent effects on norovirus infections and clinical symptoms among Mexican children.

BACKGROUND: The effect of vitamin A supplementation on viral gastrointestinal infections among young children living in developing countries remains unclear. METHODS: The effect of vitamin A supplementation on norovirus (NoV) infection among 127 Mexican children 5-15 months of age was studied in a randomized, placebo-controlled trial during June-August 1998. Stool samples collected every 2 weeks and after diarrheal episodes were screened for NoV and characterized at the genogroup level (GI and GII). RESULTS: Of the stool samples collected, 29.9% were positive for NoV, and NoV GI and NoV GII were found in 55.4% and 46.4% of the positive samples, respectively. Vitamin A supplementation reduced the prevalence of NoV GII infections (rate ratio [RR], 0.60 [95% confidence interval {CI}, 0.20-0.82]), increased the length of both NoV GI and GII shedding, and decreased the prevalence of NoV-associated diarrhea (RR, 0.51 [95% CI, 0.26-0.97]). CONCLUSIONS: These findings suggest that NoV is an important cause of pediatric diarrhea in this study population and that vitamin A supplementation has divergent effects on specific outcomes of NoV infection.