Humanity has witnessed sagas of wars since history. However, there is one war that is raging on incessantly every single day—it is the one between the ‘good’ bacteria and the ‘bad’ bacteria in our digestive gut! While the ‘bad’ bacteria are always trying to hook themselves up to our intestinal walls, the ‘good’ ones are nudging them away and confiscating those binding sites. In a recent study, scientists from the Indian Council of Agricultural Research (ICAR)-National Dairy Research Institute, Karnal, have observed this competition closely and have identified some proteins involved in this interaction. They have also produced microbeads, embedded with these proteins, that has the potential for oral administration to fight pathogenic bacteria.
Our intestine is coated with slimy mucus, which contains a complex mixture of carbohydrates and proteins. Some of these proteins bind to the receptors, which are projections on the microbes, thus preventing them from attaching to the gut surface. This mucous layer is sloughed off from time to time, removing harmful bacteria from our gut.
However, some harmful bacteria succeed in binding to the cell lining through their surface receptors, beating the good, probiotic bacteria. In this study, the researchers have studied one kind of gut receptor binding protein, called Mub protein, used by the probiotic bacteria Lactobacillus plantarum. They isolated the Mub protein and tested how good it was in preventing pathogenic bacteria from binding to human cells. To their surprise, these proteins did an excellent job and inhibited the binding of a pathogenic strain of bacteria by 81%.
“The mode of action is basically via pathogen displacement or exclusion or competition with the pathogens for the binding receptors on gut epithelial cells and thus, expediting pathogen clearance from the gut”, says Dr Jai Kumar Kaushik from ICAR-NDRI, who is the lead author of the study published in the journal Scientific Reports.
The researchers believe that this protein could soon act as supplements to combat pathogenic bacteria in the gut. They produced a small portion of the recombinant Mub protein and further explored if they could be orally delivered as an antibacterial agent in our gut. They created small microspheres or microbeads with the protein, which could be used to provide the Mub protein at the right place and amount in our gut. These microbeads were found to be stable and effective at 37oC, the average temperature of our body.
Interestingly, the researchers observed that the Mub proteins were more effective than the bacteria that produce them in preventing the pathogens from binding to the gut cells. Although similar hydrophobic interactions were observed between the gut cells and the encapsulated protein, the smaller size of the proteins helped them to percolate easily and blanket the cells and tissues, cutting off access to pathogens.
These findings of the study provide a better understanding of the interactions among the gut microbes, which have direct implications on our health. Although the intake of probiotic bacteria, in yoghurt and other fermented products, is recommended to ward off the pathogens, they still might contribute towards the evolution of drug resistance in bacteria, which is a concern. The encapsulation of proteins in the form of microbeads, as demonstrated in the study, offers a better replacement to antibiotics and the probiotic bacteria themselves.
“Antibiotic-resistant probiotics organisms are also playing a role in the development of antimicrobial resistance. Therefore, instead of the live probiotic organisms, we used their surface active proteins”, explains Dr Kaushik. “However, these proteins are only for the highly targeted purpose of inhibiting or excluding the pathogens, and cannot replace other health-promoting functions of probiotics”, he cautions.
At a time when the healthcare industry is struggling to deal with antibiotic resistance, a simple product like the Mub protein microbeads might provide an antibiotic-free approach or in combination for effectively fighting against disease-causing gut bacteria.