Evaluation of safety of Bifidobacterium and Lactobacillus strains and their synbiotic combination with isomalto-oligosaccharides against LPS-induced inflammation in murine macrophages

• Published in: Food bioscience 2024-10, Vol.61, p.104922, Article 104922
• Main Authors: Rawat, Anita, Matta, Tushar, Bhattacharya, Arka, Kumar, Ajay, Khan, Rehan, Patil, Prabhu B., Saroha, Tanu, Rajarammohan, Sivasubramanian, Bishnoi, Mahendra, Kondepudi, Kanthi Kiran
• Format: Article
• Language: English
• Subjects: Anti-inflammatory effect; Bifidobacterium; Biogenic amine; Isomalto-oligosaccharides; Lactobacillus, mucin; Safety; Synbiotics
• ISSN: 2212-4292
• DOI: 10.1016/j.fbio.2024.104922

In this study, the safety of Bifidobacterium longum Bif10, Bifidobacterium breve Bif11, Lacticaseibacillus rhamnosus LAB3, and Lactiplantibacillus plantarum LAB39 was evaluated using in-vitro, genomics, and in-vivo approaches. In the in-vitro safety studies, mucin degradation, biogenic amine production and cytotoxicity on HEK-293 cells by these strains were evaluated. Whole genome sequencing and bioinformatics analysis were carried out to identify the genes responsible for mucin degradation, biogenic amine production, antibiotic resistance, and virulence factors. In-vivo safety was assessed after acute, subacute, and sub-chronic oral feeding with respective strains to the mice as per revised OECD guidelines. Histopathological examination, gut permeability, hematological, blood biochemistry, and oxidative stress were evaluated after sacrificing the animals. Further, the compatibility of the four strains was assessed and their synbiotic combination with isomaltooligosaccharides (IMOs) was evaluated for its potential in alleviating lipopolysaccharide (LPS) induced inflammation in murine macrophages. In-vitro studies indicated that the strains do not produce biogenic amines and were non-cytotoxic to HEK-293 cells. Whole genome analysis suggested a lack of transferable antibiotic-resistance genes or potentially lethal virulence factors and genes for biogenic amines. In vivo studies showed that the bacterial strains did not affect the health parameters related to blood or induce histological alterations in the vital organs. The four strains were compatible with each other and their synbiotic blend efficiently curtailed LPS-induced oxidative stress, inducible nitric oxide and proinflammatory cytokine production. Given these observations, Bif10, Bif11, LAB3, and LAB39 can be deemed safe and their synbiotic blend with IMOs could impart anti-inflammatory effects. [Display omitted]