Advances in Micro-Biome Based Therapeutics
Thadomal Shahani Engineering College
There are over 100 trillion symbiotic micro-organisms that are present on and within human beings. One of the most well studied human microbiota is the gut microbiota, which is even considered to be an “essential organ” that influences the host’s metabolism, immune and endocrine function. These microbes are also considered to be potential sources of novel therapeutics.
A lot of research and work is going on in the field of medicine to use microbiome-based therapies for treating diseases. One of the biggest challenges in microbiome research is to determine cause and its effect on the host and to design microbiome-based therapies that might give a favourable outcome. Some of the advances in microbiome based therapies are classified in the diagram below.
Popular microbiome-based therapies involve administration of probiotics, which involves alteration of the microbial composition in the gut through administration of live microbes. Most well studied probiotics are Lacto bacillus, Bifido bacterium and Saccharomyces boulardii. Probiotics are administered for conditions associated with gastro intestinal conditions like diarrhoea; conditions in infants like infant colic, necrotizing enterocolitis and sepsis; dental disorders; conditions related to allergy and other conditions like acne, urinary tract infections etc. However, there is little evidence to support the efficacy of probiotics. An alternative approach to probiotics is prebiotics. In prebiotics certain compounds are consumed with the purpose of affecting microbiome composition in a positive way. Examples of prebiotic compounds include fructans that can stimulate lactic acid bacteria selectively, Galacto-oligosaccharides (GOS) can greatly stimulate Bifidobacteria and Lactobacilli.
Prebiotics like probiotics are relatively unspecific in approach and there is still a need for further studies on it to fully understand the effects of it on different bacterial species. Currently, a successful FDA-approved microbiome-based treatment is fecal microbiota transplantation (FMT). FMT is a novel investigative treatment for the treatment of Clostridium difficile infection, where fecal matter from a healthy donor is transplanted to the recipient. It aims to change the recipients gut microbial composition and provide health benefit.
Scientists are trying to come up ways to synthetically engineer some gut microbiota to treat diseases and for research purposes to observe its response induced in the body. They have come up with change the composition of gut bacteria to produce therapeutic molecules to treat metabolic conditions, kill pathogens and initiate immune response to cancer. Synthetic biologists have come up ways to engineer a strain of Escherichia coli in such a way that it is able to produce proteins needed to correct rare metabolic problems. This is now in clinical trials. Also, in 2018, Singaporean team revealed gut microbes that they had engineered to stick to colon cancer cells and secrete an enzyme named myrosinase which transforms into an enzyme secreted by the host called glucosinolates which is a natural component of cruciferous vegetables like broccoli which transforms to form sulphoraphane, an organic molecule which is shown to prevent carcinogenesis.
Another promising therapeutics involving gut microbiota is metabolite-based therapeutics or postbiotics. Research over a few years has revealed that the intestinal microbiota brings changes in our body’s functions by secreting certain metabolites. These metabolites act as an effective way to communicate with the host. They target downstream signalling pathways of the microbiome and this reduces the negative effects of dysregulation of metabolites involved in these pathways. Studies of human disease on animal-based models have shown great promise, for example short-chain fatty acids (SCFAs), were shown to have an anti-inflammatory effect and are altered in inflammatory bowel disease (IBD) patients.
Metabolite based interventions are advantageous because the molecules involved are present in large numbers and when they are compared to probiotics it is less toxic and the dosage and the routes of administration follow the rules of pharmacokinetics. Metabolites are present in most of the places in our body hence they can be administered by various routes. Metabolites are also generally stable in the systemic circulation and hence their concentration can be varied to a scalable number with very few side effects.
Disadvantages of metabolite-based therapeutics are that the medicines involved have shorter half-lives than administration of live bacteria; hence, repeated dosing may be required. Also, the effects of some microbiome-associated metabolites are pleiotropic and highly cell type specific. As such, further characterization and studies need to be done to fully understand the effects of different metabolites and its potential side effects of postbiotics.
To conclude, it seems that the era of microbiome-based therapies has begun and there is still a lot of research pending in this field. The future of microbiome-based therapies seems bright and will continue to grow.