Screening and Identification of Probiotic Lactobacilli from the Infant Gut Microbiota to Alleviate Lead Toxicity.

Lead (Pb2+) exposure cause a potential hazard to human health and the ecological environment; however, prevention and treatment of Pb2+ toxicity remain problems. The aim of this study is to isolate a novel probiotic lead (Pb2+)-resistant Lactobacillus strain from the infant gut microbiota and to determine whether they have the probiotic properties and investigate its preventive and therapeutic effects in the early-life Pb2+ exposure mouse model. In the present study, a total of 64 Pb2+-resistant colonies were isolated from the infant gut microbiota. Of these colonies, SYF-08, identified as Lacticaseibacillus casei, exhibited a Pb2+-binding capacity and Pb2+ tolerance. The in vivo study showed that SYF-08 treatment could effectively reduce Pb2+ levels in the blood, alleviate Pb2+ enrichment in bone and brain tissues, and recover the intestinal and brain damage in both dams and offspring. SYF-08 treatment also improved the antioxidant index in the liver and kidney tissues, while increasing the diversity of the intestinal microbiota of the offspring. The results of the in vitro and in vivo studies suggest that SYF-08, isolated from infant fecal samples, is a promising candidate probiotic against Pb2+ toxicity.

Effects of short term lead exposure on gut microbiota and hepatic metabolism in adult zebrafish.

Lead (Pb) is one of the most prevalent toxic, nonessential heavy metals that has been associated with a wide range of toxic effects in humans and environmental animals. Here, effects of short time exposure to 10 and 30 µg/L Pb on gut microbiota and hepatic metabolism were analyzed in adult male zebrafish. We observed that both 10 and 30 µg/L Pb increased the volume of mucus in the gut. At phylum level, the abundance of α-Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut when treated with 30 µg/L Pb for 7 days. In addition, the 16S rRNA gene sequencing for V3-V4 region revealed a significant change in the richness and diversity of gut microbiota in 30 µg/L Pb exposed group. A more depth analysis, at the genus level, discovered that 52 gut microbes identified by operational taxonomic unit analysis were changed significantly in 30 µg/L Pb treated group. Based on GC/MS metabolomics analysis, a total of 41 metabolites were significantly altered in 30 µg/L Pb treatment group. These changed metabolites were mainly associated with the pathways of glucose and lipid metabolism, amino acid metabolism, nucleotide metabolism. In addition, we also confirmed that the transcription of some genes related to glycolysis and lipid metabolism, including Gk, Aco, Acc1, Fas, Apo and Dgat, decreased significantly in the liver of zebrafish when exposed to 30 µg/L Pb for 7 days. Our results observed that Pb could cause gut microbiota dysbiosis and hepatic metabolic disorder in zebrafish.

Gut microbiota limits heavy metals burden caused by chronic oral exposure.

Environmental exposure to pollutants such as heavy metal(s) is responsible for various altered physiological functions which are detrimental for health. The gut microbiota is critical for intestinal homeostasis but its role on xenobiotic handling is not fully understood, especially when continuous sub-chronic exposure is addressed. We first confirmed the essential role of the intestinal microbiome to limit heavy metal body burden by using germ-free mice following 6-weeks oral exposure. Significant increases of cadmium and lead absorption and dissemination in blood and target organs were measured in germ-free mice when compared with conventional specific pathogen free (SPF) mice. Besides the "barrier" function of the luminal microbiota, this may involve specific host-genes such as metallothioneins, which are differentially expressed in the gastrointestinal tract of each group of mice. Considering genes relevant for divalent metal transporters and oxidative pathways, significant differences in basal gene expression were measured between control and germ-free mice. Moreover, the magnitude of induction of these genes upon stimulation by heavy metals varied greatly depending on the dose and type of metal as well as the microbial status of the animal. Collectively, these data illustrate the complex host-microbes interplay occurring with environmental pollutants inside the gut.

Oral lead exposure induces dysbacteriosis in rats.

OBJECTIVES: Lead's (Pb(II)) possible role in intestinal pathologies of microbial etiology remains mostly unknown. The aim of this study was to examine the effects of lead on the gut microbial community and its interactions with rat intestinal epithelium. METHODS: The lead-induced changes in different intestinal microbial groups (lactose-positive lac(+) and -negative lac(-) E.coli strains, lactobacilli and yeasts) were followed separately by the colony-forming unit (CFU) method. Samples were taken from outbred white rats subjected to different exposure schedules. Additionally, the impact of different lead doses on microbial adhesion to cultured intestinal cells (IEC-6) was investigated. Finally, the lead accumulation and distribution were measured by means of atomic absorption spectrometry. RESULTS: For the first time it was shown that oral lead exposure causes drastic changes in the gut microbial community. Proportional to the lead dose received, the relative number of lactose-negative E.coli cells increased dramatically (up to 1,000-fold) in comparison to the other microbial groups during 2 wk of exposure. Considering the number of microbes in the intestine, such a shift in intestinal microflora (dysbacteriosis) is very significant. Adhesion studies showed certain stimulating effects of lead on E. coli attachment to rat intestinal epithelium as compared to Lactobacillus attachment. CONCLUSIONS: The mechanisms providing the apparent competitive success of the lac(-) group are unclear but could be related to changes in surface interactions between microbial and host cells. This study may provide important clues for understanding the pathological effects of metal dietary toxins in human beings.

Intracellular survival of Staphylococcus aureus due to alteration of cellular activity in arsenic and lead intoxicated mature Swiss albino mice.

The role of heavy metals like arsenic (As) and lead (Pb) as environmental toxicants is established. However, the exact mechanism of their effect on immunocompetent cell activity is not well known. Staphylococcus aureus is a virulent pathogen that has the ability to cause a variety of potentially life-threatening infections. The objective of our study was to demonstrate in an experimental mouse model of bacteremic S. aureus infection, bacterial clearance from blood and spleen in arsenic, lead treated and control group of mice. Bacterial density was measured in blood and spleen after 0, 24, 48 and 72 h post-infection. Our findings show a significant increase in bacterial load in blood (P<0.025 for arsenic and P<0.01 for lead) and delayed bacterial clearance by spleen in both arsenic (P<0.05) and lead (P<0.025) treated groups as compared to control, thus highlighting an immuno-compromised state following heavy metal exposure. To further elucidate immunomodulatory effects of both arsenic and lead, cell function studies were performed on splenic macrophages (M(phi)) isolated from lead and arsenic treated as well as control group of mice. Our findings show a decrease in cell adhesion property (P<0.005) of splenic M(phi)s from 2.9925+/-0.053 in control to 1.395+/-0.106 in arsenic and 0.8835+/-0.0106 in lead treated mice at 60 min. Morphologic alteration of the splenic M(phi)s showed an increase (As: P<0.05, Pb: P<0.0005) in both arsenic (6.876+/-0.3287%) and lead (16.55+/-1.051%) treated mice to control (2.649+/-1.238%) which may be responsible for the formers' reduced functional status. The chemotactic index, a measure of chemotactic migration of the macrophages toward immune serum, was 16.43+/-1.007 in control cell and was reduced (P<0.0005) to 4.19+/-0.393 in arsenic and 2.92+/-0.649 in lead treated mice at 60 min. These altered cell functions could probably explain the intracellular survival of S. aureus but such a causal relationship awaits further detailed examination.