Advancements in the field of synthetic biology, genetic engineering and genome sequencing technologies have provided the opportunity to improve the functional repertoire of prevailing microbes. We summarise a recent chapter in Probiotic Research in Therapeutics that explored the field of designer probiotics and the potential prospects for their clinical translation.
Patho-biotechnology refers to the exploitation of pathogenic microbes for beneficial utilisation in the food industry as well as biomedicine. It involves three distinct approaches. The first comprises of utilising attenuated bacterial pathogens in vaccine or drug delivery mechanisms. The second approach focusses on the direct application of pathogen-related immunogenic proteins. The final approach deals with equipping probiotic/non-pathogenic microbes with genetic constructs to overcome issues during food production, storage conditions and also the body defence mechanisms. This final strategy further encompasses three strategies: the storage and delivery of probiotics, augmenting host colonisation and developing recombinant probiotics (designer probiotics).
The applications of probiotics are expanding from food processing and general microbiology, towards fields of oncotherapy, infectious diseases, functional nutraceuticals, allergology, skin care, veterinary, livestock, psycho neuroendocrinology and gastroenterology.
The increase in antibiotic-resistant pathogens, along with slow antibiotic development, has led researchers to shift focus towards identifying alternative means. This includes improving the functional repertoire of existing probiotics. Living therapeutics, through engineering microbes, are efficient in fighting challenging medical problems, such as cancer and autoimmune disease. For example, such engineered probiotics can provide targeted in situ delivery of antitumor agents, while avoiding the damaging effects on healthy cells caused by systemic treatment.
Here we summarise some key applications of probiotics within the medical industry:
In the past decade, designer probiotics have appeared to aid anti-cancer therapy as prodrugs and diagnostic tools by improving targeting. Probiotics can also be utilised to express anti-cancer compounds. For example, researchers have found that engineered Lactococcus lactis expressing cell wall-anchored or secreted forms of human TRAIL protein induced apoptosis in human colon adenocarcinoma cell lines.
Inflammatory and autoimmune disease
Genetically designed lactic acid bacteria can be used for the delivery of vaccines against toxins and infectious diseases. Experts can also employ these for delivering immunotherapeutics to treat inflammatory diseases. Another example is Bifidobacterium longum which researchers engineered to produce alpha-melanocyte-stimulating hormone, an anti-inflammatory peptide, against an alpha-MSH ulcerative colitis model in vivo.
Lack of antibiotic options has led the search for alternative means to control the present antimicrobial resistance crisis. One of the alternative methods involves the use of novel synthetic biology-driven antimicrobial strategies, such as designer probiotics. For example, engineered Lactobacillus gasseri expressing streptococcal M6 protein has been found to protect mice against streptococcal pharyngeal infections.
Metagenomics-wide association studies have revealed the association of metabolic disorders with altered bacterial genes and their respective metabolic functions. Engineered probiotics as dietary supplements or topical agents can promote normal physiology along with high immunity. For example, delivery of IL-10 and type 1 diabetes auto-antigen via designed L. lactis prevented diabetes development in non-obese mice.
Exploring strategies for using designer bacteria as delivery vectors for vaccines that stimulate durable humoral and cellular immunity, opens up novel opportunities for their applications in the healthcare industry. For example, researchers have found that designer probiotic-mediated vaccinations against enterotoxigenic Escherichia coli, Yersinia pseudotuberculosis, Streptococcus pneumoniae and Salmonella enterica elicited specific and fast immune responses in vivo.
A class of probiotics known as ‘psychobiotics’ can produce and deliver neuroactive compounds to act on the gut-brain axis. They can also deliver an antidepressant effect on the host organism. Findings have suggested the potential application of microbial-based therapeutic strategies in mental health. This is because there appears to be an association of gut microbiota with autism and depressive illness.
Nutraceuticals, such as omega-3 long chain polyunsaturated fatty acids (LC-PUFA), are valuable due to their actions on human nutrition, neurodevelopment status, and prevention of cardiovascular disease. Experts can use micro-organisms for bulk supply of nutraceuticals. They are beneficial as they have the ability to survive under stressful conditions within the gut.
Exploiting microbiota is an emerging trend. Researchers can tailor designer probiotics to express beneficial proteins, to deliver biomaterial, to destroy infectious pathogens and to combat cancers, infectious and metabolic diseases. Most importantly, this field could lead to cuts in production, delivery and storage costs compared to conventional therapies. However, concerns about safety and consumer opinion remain and need to be further explored.
Image credit: By RomarioIen – canva.com