Can tailored nanoceria act as a prebiotic? Report on improved lipid profile and gut microbiota in obese mice
Microbiome modulation is a pillar intervention to treat metabolic syndrome, prestages, and cascade of related pathologies such as atherosclerosis, among others. Lactobacillus and Bifidobacterium probiotic strains demonstrate efficacy to reduce obesity, dyslipidemia, and improve metabolic health. Novel prebiotic substances composed with known probiotics may strongly synergize health benefits to the host. The aim of this study was to evaluate beneficial effects of Lactobacillus and Bifidobacterium strains (probiotics) if composed with nanoceria (potential prebiotic) to reduce cholesterol levels and restore gut microbiota in obese mice.
Materials and Methods
Two lines of mice were used in the study: BALB/c mice (6–8 weeks, 18–24 g) and CBA mice (11–12 months, 20–26 g); experimental animals were fed by fat-enriched diet 3 weeks before the evaluation. Animals were divided into groups to test probiotic strains and nanoceria. All groups received probiotic strains orally and cerium dioxide orally or intravenously in various composition. A group of untreated animals was used as a control. Cholesterol level and gut microbiota of mice were studied.
Cerium dioxide nanoparticles, probiotic strain L. casei ІМV В-7280, and composition B. animalis VKB/B. animalis VKL applied separately and in different combinations all reduced at different levels free and bound cholesterol in blood serum of mice fed by fat-enriched diet. The combination of 0.01 M nanoceria and probiotic strain L. casei ІМV В-7280 resulted in the fastest cholesterol level decrease in both young and mature animals. Oral administration of CeO2 applied alone reduced the number of microscopic fungi in the gut of mice and Gram-positive cocci (staphylococci and/or streptococci). Application of L. casei IMV B-7280 as a probiotic strain increased most significantly the number of lactobacilli and bifidobacteria in the gut of mice. The most significant normalization of gut microbiota was observed after oral administration of alternatively either L. casei IMV B-7280 + 0.1 M CeO2 or L. casei IMV B-7280 + 0.01 M CeO2.
Dietary application of nanoceria combined with probiotic strains L. casei IMV B-7280, B. animalis VKB, and B. animals VKL has significantly reduced both free and bound cholesterol levels in serum. Simultaneous administration of probiotics and cerium nanoparticles as a prebiotic, in various combinations, significantly enhanced positive individual effects of them on the gut microbiota spectrum. The presented results provide novel insights into mechanisms behind nutritional supplements and open new perspectives for application of probiotics combined with substances demonstrating prebiotic qualities benefiting, therefore, the host health. Follow-up translational measures are discussed to bring new knowledge from lab to the patient. If validated in a large-scale clinical study, this approach might be instrumental for primary and secondary prevention in obese individual and patients diagnosed with diabetes. To this end, individualized prediction and treatments tailored to the person are strongly recommended to benefit the health condition of affected individuals.
KeywordsPredictive preventive personalized medicine Nanoceria Nanoparticles Prebiotic Probiotic Obesity Metabolic syndrome Atherosclerosis Animal model Improved metabolism In vivo Microbiome Gut microbiota Lactobacillus Bifidobacterium Cholesterol Phenotype
The study was conducted with the support of the State Agency on Science, Innovations and Informatisation of Ukraine.
Rostyslav Bubnov created concepts and designed the study, participated in experiments, performed ultrasound investigations and analytical procedures, and drafted discussion and outlook. Lidiia Babenko and Liudmyla Lazarenko performed experiments on animals, corresponding analysis, and statistical evaluation, and created the first draft of manuscript. Maryna Kryvtsova, Nadiya Zholobak, and Oleksandr Shcherbakov participated in analytical approaches. Olga Golubnitschaja contributed to main concepts of the study, data interpretation and multidisciplinary aspects, and strengthened the expertise related to predictive, preventive, and personalized medicine. Mykola Spivak supervised the project and contributed to the data interpretation.
All authors read and approved the final manuscript.
Compliance with ethical standards
The authors declare that they have no competing interests.
Ethics approval and consent to participate
This study has been approved by the ethics committee of institutional review board and Special Academic Council on Doctoral Thesis of D.K. Zabolotny Institute of Microbiology and Virology of the National Academy of Sciences of Ukraine (protocol N 7 issued 03.07.2018).
No human subjects were included into the study.
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