Writing in the journal Microbiome, researchers successfully isolated molecules secreted by a yeast contained in kefir yoghurt that has proved efficacious against the causative agent of cholera.
Further research highlighted the molecules’ anti-inflammatory effect in tackling the so-called "cytokine storm" – the extreme immune response responsible for the deaths of so many COVID-19 patients.
Commenting on the molecule’s apparent ability to restore balance to the immune system, Professor Raz Jelinek, the Vice President and Dean for Research & Development at Ben-Gurion University (BGU) said, “Our research illuminates for the first time a mechanism by which milk fermented probiotics can protect against pathogenic infections and aid the immune system.
"These results are notable since this is the first demonstration that virulence of human pathogenic bacteria can be mitigated by molecules secreted in probiotic milk products, such as yogurt or kefir," he adds.
“Following promising results in animal models, we look forward to administering these drug candidates to humans, for example to patients who are experiencing a cytokine storm due to COVID-19 infection, or people suffering from acute inflammatory bowel pathologies, such as Crohn's disease."
The molecule in question, tryptophol acetate is secreted by the fungus Kluyveromyces marxianus, which is predominantly found in probiotic milk-fermented microorganism mixtures such as yogurt and kefir.
The team believes the study is the first report of its production by a yeast and particularly its role as a signalling molecule, having previously been found in plants and algae.
They suggest that tryptophol acetate’s anti-bacterial effect involves disrupting communication among the bacterial cells and interfering in biofilm assembly, which play roles in cholera’s progression.
"In a reality where antibiotic-resistant bacteria are becoming an imminent threat, the novel molecules discovered by BGU scientists pave a completely new path for fighting bacterial infections by disrupting cell-cell communications in pathogenic bacteria,” said Josh Peleg, CEO of BGN Technologies, BGU's technology transfer company.
“Moreover, the dramatic anti-inflammatory activities of the molecules may open new avenues for therapeutics and scientifically proven probiotic food products.
"Years of breakthrough research have now reached a validation point that led to the establishment of a biopharma company for the further development and clinical evaluation of this exciting new technology that can potentially revolutionise the treatment of bacterial infections as well as inflammatory conditions."
Led by Orit Malka, a Ph.D. student in Prof Jelinek’s laboratory, the team suggested in its conclusion the existence of a as yet-unrecognised mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture.
“Tryptophol acetate was shown to disrupt quorum sensing (cell–cell communication) pathways of the human gut pathogen V. cholerae,” the team wrote.
“Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism coexistence in multi-population environments, such as probiotic foods and the gut microbiome.
“This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.”
Published online: doi.org/10.1186/s40168-021-01027-8
“Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites.”
Authors: Orit Malka et al.