About this Research Topic
The gut microbiome plays a key role in human health and disease and continues to be an area of strong scientific interest. Disruption of the gut microbiome can have negative impacts on heath and is associated with a wide range of conditions from infectious diseases like C. difficile, to metabolic disorders, gastrointestinal illnesses and neurologic conditions. The most profound disrupters of the gut microbiome are antibiotics, and these can also lead to the emergence of antimicrobial resistance in the gut microbiome. There is much interest in developing new interventions to both prevent and treat conditions associated with changes or disruptions in the gut microbiome.
There are numerous interventions currently in development which target the gut microbiome, but development of these drugs provides its own challenges that can be different than drug development for other disease indications. Some of these drugs are meant to maintain the overall health of the microbiome while others are meant to specifically intervene in disease processes by altering microorganisms in the gut microbiome. These novel treatments range widely from medicinal foods like probiotics and prebiotics, to fecal microbiome transplants, to the use of bacteria as drugs, to more traditional pharmaceutical approaches using small molecules and biologically-derived products.
There are many examples of the challenges when developing drugs for the gut microbiome. Most of these drugs are delivered orally, and are then expected to remain in the intestine. From the manufacturing standpoint, this is both an advantage in terms of the required level of purity of the drug as well as a disadvantage, as the cost of the product must be kept low to assure use. Oral delivery also presents formulation challenges as the drugs must be protected from stomach acidity and subsequently delivered to the appropriate location in the intestine. The active ingredients themselves also have to be able to survive in the harsh environment of the GI tract. There are also regulatory challenges for example, alteration of the composition of the gut microbiome is not currently accepted as an endpoint for drug approval by regulatory agencies. Thus, meaningful clinical endpoints have to be included in the development program. For animal studies, challenges include identification of appropriate animal disease models as the gut microbiome of animals may not be representative of the human gut microbiome. Similarly, for clinical development there is little consensus on what represents a “normal” gut microbiome, and validated biomarkers are lacking for microbiome-associated diseases. A further challenge is that analysis of the content of the microbiome itself is still evolving without standardization in terms of methodology and data analysis making clinical development more difficult.
The unique challenges for development of interventions for the gut microbiome range across all aspects of drug development, and thus a special issue of Frontiers in Microbiology is being prepared that focuses on these various challenges and lessons learned in developing drugs for the gut microbiome and prevention of antimicrobial resistance in the gut which will encompass all disciplines of drug development.
There are numerous interventions currently in development which target the gut microbiome, but development of these drugs provides its own challenges that can be different than drug development for other disease indications. Some of these drugs are meant to maintain the overall health of the microbiome while others are meant to specifically intervene in disease processes by altering microorganisms in the gut microbiome. These novel treatments range widely from medicinal foods like probiotics and prebiotics, to fecal microbiome transplants, to the use of bacteria as drugs, to more traditional pharmaceutical approaches using small molecules and biologically-derived products.
There are many examples of the challenges when developing drugs for the gut microbiome. Most of these drugs are delivered orally, and are then expected to remain in the intestine. From the manufacturing standpoint, this is both an advantage in terms of the required level of purity of the drug as well as a disadvantage, as the cost of the product must be kept low to assure use. Oral delivery also presents formulation challenges as the drugs must be protected from stomach acidity and subsequently delivered to the appropriate location in the intestine. The active ingredients themselves also have to be able to survive in the harsh environment of the GI tract. There are also regulatory challenges for example, alteration of the composition of the gut microbiome is not currently accepted as an endpoint for drug approval by regulatory agencies. Thus, meaningful clinical endpoints have to be included in the development program. For animal studies, challenges include identification of appropriate animal disease models as the gut microbiome of animals may not be representative of the human gut microbiome. Similarly, for clinical development there is little consensus on what represents a “normal” gut microbiome, and validated biomarkers are lacking for microbiome-associated diseases. A further challenge is that analysis of the content of the microbiome itself is still evolving without standardization in terms of methodology and data analysis making clinical development more difficult.
The unique challenges for development of interventions for the gut microbiome range across all aspects of drug development, and thus a special issue of Frontiers in Microbiology is being prepared that focuses on these various challenges and lessons learned in developing drugs for the gut microbiome and prevention of antimicrobial resistance in the gut which will encompass all disciplines of drug development.
Keywords: Gut microbiome, drug development, oral delivery, antibiotic-mediated dysbiosis, antimicrobial resistance
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