{"id":481550,"date":"2024-01-10T03:30:01","date_gmt":"2024-01-10T08:30:01","guid":{"rendered":"https:\/\/platohealth.ai\/microbiome-innovation-have-we-forgotten-the-basics\/"},"modified":"2024-01-10T10:41:58","modified_gmt":"2024-01-10T15:41:58","slug":"microbiome-innovation-have-we-forgotten-the-basics","status":"publish","type":"post","link":"https:\/\/platohealth.ai\/microbiome-innovation-have-we-forgotten-the-basics\/","title":{"rendered":"Microbiome innovation: have we forgotten the basics?","gt_translate_keys":[{"key":"rendered","format":"text"}]},"content":{"rendered":"
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Here, Chrysi Sergaki from the Medicines and Healthcare products Regulatory Agency (MHRA), UK, explores how innovators and regulators can navigate the challenges affecting the development and regulation of microbiome therapeutics to bring safe and efficacious therapies to patients as soon as possible.<\/p>\n<\/div>\n

\n\"Microbiome\"Microbiome<\/div>\n

The human microbiome is a key player in our understanding of health and disease. This network of trillions of microorganisms residing in our gut and across our body has opened new avenues in medicine, offering the promise of innovative, minimally invasive therapies. As late-stage clinical development, manufacturing, quality control processes and regulation for microbiome-based treatments evolve, standardisation becomes a critical and complex challenge. This article discusses the complexity of microbiome-based medicinal products and the novel challenges being encountered to characterise and measure this complexity in a robust manner as they progress through the different stages of clinical development that can delay the progress of products to the market.<\/p>\n

The gut microbiome: a therapeutic goldmine<\/h2>\n
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The potential of manipulating and harnessing the gut microbiome to treat and prevent disease, has seen a wave of clinical trials emerge\u201d<\/p>\n<\/div>\n

The human gut is a dynamic ecosystem saturated with a diverse array of bacteria, viruses, fungi and other microorganisms. This intricate network is vital for maintaining gut health, our immune system, and even mental wellbeing. Its disruption has been linked to a wide range of diseases, including inflammatory bowel diseases, cancer, metabolic disorders and neurodegenerative conditions. Recognition of the potential of manipulating and harnessing the gut microbiome to treat and prevent disease, has seen a wave of clinical trials emerge. However, as this field expands, it faces an equally growing array of conceptual and technical challenges.<\/p>\n

Conceptual challenges: basic ecosystem biology and microbiology<\/h2>\n

The basis of many challenges is the dynamic nature of the microbiome, which is vastly underexplored and not well understood. The microbiome is an ever-changing ecosystem, influenced by changes in our diet, exercise, environment and health status, to name a few. It is essential to recognise that changes in the microbiome\u2019s composition and function are not exclusive to individuals with diseases. This ecosystem sensitivity, along with the complexity of the human body and lifestyle, makes it difficult to understand how the microbiome is affected by its environment and how these changes impact us.<\/p>\n

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All microbiomes, even healthy ones, can contain pathogenic microbes\u201d<\/p>\n<\/div>\n

To add to the complexity, the dynamic nature of microbes means that beneficial microbes can become pathogenic and vice versa depending upon the environment in which they exist.1<\/sup> All microbiomes, even healthy ones, can contain pathogenic microbes, without causing inflammation or infection, such as Clostridium difficile.<\/em> C. difficile<\/em> can cause serious infections for some but has also been found in the microbiomes of healthy individuals with no problems. The potential of each microbe to become pathogenic can also be dictated by the environment, even leading to dormancy, frequently overlooked by strictly DNA-based investigation. This lack of comprehensive understanding of microbiome ecology and dynamics affects all stages of innovation; from describing the mechanism of action, to dosing, toxicity, efficacy and ultimately the success of clinical trials.<\/p>\n

\"Microbiome<\/p>\n

\"Microbiome<\/p>\n

Disturbing an ecosystem can lead to loss of biodiversity, population imbalances, habitat destruction, changes in function (eg, metabolism and nutrient cycling), loss of resilience and increased vulnerability to disease.2<\/sup> Manipulating the microbiome requires a level of ecosystem disturbance and predicting and controlling the effect of these interventions \u2013 both on the microbiome and the human body \u2013 requires better understanding of the microbial ecology of the human body, which is not a simple task.<\/p>\n

Beyond bacteria, the microbiome is home to a less-explored realm of fungi, archaea, viruses and parasites that have a role to play within the ecosystem, which is not well studied or understood. This dynamic microbial interaction includes competition for nutrients, cross-feeding and genetic exchange, among other interactions, contributing to the fluctuation in microbiome composition and functionality. It is crucial to emphasise that the dynamics of these events are highly complex, interconnected and, notably, vary significantly from person to person.<\/p>\n

Quality control: can we trust our data?<\/h2>\n
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Lack of confidence in data has increased concerns about the field over the years\u201d<\/p>\n<\/div>\n

Technical challenges make understanding the microbiome as an ecosystem even more difficult. While the evolution of omics technologies has revolutionised microbiome research, the data generated is compromised by the inherent bias of these methodologies and the lack of effective standardisation. From sampling and storage to extraction and analysis, methods can vary and give different results, leading to contradictory findings.3<\/sup> This lack of confidence in data has increased concerns about the field over the years, a problem which becomes even greater for understudied microbes like fungi and viruses.<\/p>\n

As technology progresses, we have started questioning the taxonomy and the definition of strain, as well as the functional capabilities of microbes, considering genome structure, phenotypic plasticity, functional redundancy and the regulation of gene expression at a fundamental level.4<\/sup> This not only poses issues for intellectual property (IP) but also regulatory challenges as the product progresses to clinical trials.<\/p>\n

The imperative for standardisation<\/h2>\n

\"Microbiome<\/p>\n

\"MicrobiomeThe complexity and potential variability in microbiome therapies necessitates robust standardisation across all stages of research and development<\/a>. Efforts to standardise microbiome therapies are already underway, with several reference reagents available and international studies revealing the variability in methodologies across the world.5,6<\/sup> These standards should be robust and applicable for the evolving field, accommodating advances in microbiome science and technology. Standardised methods offer several benefits:<\/p>\n