Scientific Foresight (STOA) By / June 21, 2021

Microbiomes: Small little things that run life on Earth

STOA Chair Eva Kaili (S&D, Greece) opened the workshop by setting the scene on the role of microbiomes in health and the issues related when their balance is upset, as well as the related threats of antimicrobial resistance (AMR) and healthcare-associated infections (HAIs).

Written by Gianluca Quaglio with Virginia Mahieu.

‘Microbiota’ is a collective term referring to the reservoirs of micro-organisms living in the human body, in animals and in the environment. They are nearly ubiquitous, both in our soils and in our gut, working behind the scenes, but providing vital support to our health and well-being. Micro-organisms always live in microbial communities, which are quite diverse. Although the terms are used interchangeably, there is a slight difference between microbiome and microbiota. In fact, ‘microbiota’ refers to the actual organisms (‘bugs’) within a microbial community, and ‘microbiome’ to the organisms of a microbial community in its ‘theatre of activity’, i.e. taking environmental conditions into consideration, for example.

The human being has evolved with microbiomes and they are an integral part of life on Earth, although they have been relatively absent from the public consciousness. Scientific evidence of the last two decades shows the vital importance of microbiomes in our lives. The STOA workshop on the ‘Health and economic benefits of microbiomes‘ , held online on 21 May 2021, provided an insight into the importance of microbiomes in human, animal and environmental health, and how they could contribute to mitigating pollution and climate change, and boosting the European economy. Speakers illustrated the wide variety of applications and impacts of microbiomes and highlighted the ways in which their regulation at EU level could be improved.

STOA Chair Eva Kaili (S&D, Greece) opened the workshop by setting the scene on the role of microbiomes in health and the issues related when their balance is upset, as well as the related threats of antimicrobial resistance (AMR) and healthcare-associated infections (HAIs). She noted the current lack of EU regulation directly pertaining to microbiomes and stressed that it is crucial in the areas of healthcare and environmental sustainability that policy-making is guided by scientific and clinical evidence.

Microbiomes are vital to human, animal and environmental health

Emmanuelle Maguin, senior researcher at the French Institut National de la Recherche Agronomique (INRAE), provided an insight into the roles that microbiomes play in the human being. Microbiomes and the host-microbe interplay are well documented. The human body offers microbiomes a sort of ‘shelter’, and in return they provide a number of ‘services’, such as protection against pathogens and support to our immune system and metabolism, breaking down fibre that we cannot digest, synthesising essential compounds such as vitamins, even metabolising drugs.

In the last 60 years, industrialised societies have markedly changed our lifestyles in terms of nutrition, food systems and food, physical activity, childbirth, drug treatments (including antibiotics), exposure to environmental factors etc. All these recent modifications are putting the human-microbe symbiosis at risk of progressive functional alterations.

The recent accumulation of knowledge on microbiomes radically transforms the human health paradigm inherited from our experience with infectious diseases and other pathological conditions. From a linear vision of one microbial agent and its ability to generate a disease, we have moved to a more complex situation, where the interactions between numerous environmental, host and microbiome factors determine the risk of developing a disease and possibly even the response to a given therapy.

The recent concepts of the One-Health approach and personalised medicine are integrating this complexity considering the specific history of the host, environmental exposure, and sometimes microbiome specificities and modifications over a human lifespan. However, there is still a need to advance knowledge on these multifactorial interactions. A key prerequisite for producing robust data and providing meaningful analyses is the availability and large-scale use of harmonised standards and operating procedures, as well as access to unified repositories.

This new vision necessitates reconsideration of our current health and medical approaches. This should enable us to integrate the environment-microbiome-host interactions as key elements in prevention of disease and maintenance of a healthy state, to re-examine and to create new diagnostic and therapeutic tools, and to devise the required regulatory framework for microbiome-based innovations and increase awareness of, as well as information and training in this paradigm.

The balance of microbiomes is important not only in our bodies and in nature, but also in ‘built environments’, as Elisabetta Caselli, from the University of Ferrara pointed out. Hospitals have their own microbiome, and persistent use of chemical disinfectants on surfaces leads to the selection for multi-drug antimicrobial resistant (AMR) pathogens that can cause HAIs. HAIs are a global concern, each year affecting over 4 million patients in the EU, with about 90 000 avoidable deaths and €1.1 billion of extra sanitary costs.

Modulating the hospital microbiome by using probiotic cleaning hygiene systems to reduce pathogens and AMR in clinical settings could be a new and effective method. This system, called probiotic-based sanitation (PBS), contains selected probiotic bacteria, which are non-pathogenic and also present in the human gut and diet. A number of studies that applied PBS showed a massive decrease in pathogens on surfaces compared to using chemical-based sanitation, as well as a decrease in AMR genes, while presenting no risk to hospital patients. Furthermore, it led to a considerable decrease in costs related to HAIs. The PBS approach could open new perspectives in the fight against infections of bacterial, fungal and viral origin, including SARS‑CoV‑2.

Shifting the focus from human health to that of animals and the environment, Lene Lange, of BioEconomy Research & Advisory, explained that the gut microbiome is highly relevant for the agricultural industry, particularly in the breeding of pigs, chicken and fish. Harnessing it can give a better life to livestock with less inflammation and a lower mortality rate, and could reduce the use of antibiotics and thus the threat of AMR. Animal health can be improved by analysing the gut microbiome and producing feed with beneficial effects: probiotics (beneficial microbes) and prebiotics (fibre) are anti-inflammatory components that can be added to or released through fermentation of the feed, producing a cascade of good products that strengthen the gut flora. She recommended making these gut microbiome-improving animal feed additives a part of dietary requirements in industrial animal breeding.

The speaker also noted that the same concept as HAIs, mentioned above, can be applied to natural ecosystems: ‘undisturbed’ nature offers insight into a healthy balance of microbiomes in soils, and can inform biological measures to strengthen them and reduce pesticide use (crucial for halting biodiversity loss), improve nutrition efficiency, and mitigate climate change. Furthermore, estimates of emissions from permafrost melt can be made by monitoring the soil microbiome, and study of bacteria-rich wastewater can inform soil-improvement products and track the spread and development of AMRs. Dr Lange concluded by saying that microbiomes present a scientists’ dream pool for the discovery of new enzymes, recommending that their research would benefit from becoming more cross-sectorial with EU support and given a high priority.

Microbiomes could support a circular bio-economy, but currently face regulatory gaps

To elaborate on the crucial roles of microbiomes in maintaining life on Earth and their potential role in the economy, Angela Sessitsch from the Austrian Institute of Technology spoke about how these ‘tiny little things run the Earth and the circular economies’. Microbiomes are key for ecosystem function and can be considered a natural resource. In soils, they perform vital functions: contributing to growth and nutrient cycling by fixing nitrogen and methane, breaking down plant cells, and through fermentation, all reducing expensive fertiliser needs and greenhouse gas emissions. They have a variety of important environmental uses such as breaking down organic waste, toxic compounds and plastics, and they can improve sustainable food, feed and biofuel production. Specifically, agricultural management practices can favour microbiome conditions and thus improve food production.

These potential applications for better, more sustainable agriculture and recycling can contribute to a circular bio-economy, which has been acknowledged by several organisations including the World Economic Forum (WEF), the Food and Agriculture Organization (FAO) and the Organisation for Economic Co-operation and Development (OECD), and microbiomes can substantially contribute to Sustainable Development Goals and EU Green Deal ambitions. Their many applications are also extremely promising for market growth in medical areas: they can generate economic value through products and therapies, diagnostics, predictions and personalised medicine and food. To best exploit microbiomes, the EU needs to increase awareness about them and integrate them into cross-sectorial policies.

Indeed, microbiomes are not yet regulated at the EU level. Marta Hugas from the European Food Safety Authority (EFSA) spoke about the safety and regulatory challenges of microbiome innovations. One of EFSA’s core tasks is to assess risks to human, animal and environmental health from substances linked to food and feed production The increasing role of microbiomes in health calls for a prospective mapping of their various roles into regulatory assessment, with a view to understanding their potential health impact in the various hosts.

Legal requirements under EU food law do not specify that risk assessments account for microbiomes. There is currently also no internationally agreed guidance or methodology in place to systematically assess possible effects on the microbiomes, or caused by the microbiomes, on human, animal or plant health. Translating a decrease in microbiome diversity into a functional effect is challenging, as there are currently no standards for defining a healthy microbiome.

EFSA is currently working on integrating the new scientific information on microbiomes and clarifying how it can be applied. There are suspicions that differences between animal and human microbiomes could be the reason for the differences that sometimes exist between studies and clinical trials, which raises questions as to how to interpret toxicological studies. Further questions include determining criteria for when an effect becomes adverse and establishing causality between metabolic pathways and microbiota (i.e. if a disease is the cause or the effect of microbiome imbalance). Research does not usually focus on regulatory science. EFSA will therefore soon publish the research questions the EU and Member State levels need to address from a regulatory perspective, such as the link between microbiomes and diet/toxicology.

While the field of microbiomes holds genuine promise, it is also subject to hype. Challenges remain with regard to the standardisation of terms and protocols, and credible and well-tailored information is needed. These issues were addressed by Kathleen D’Hondt, from the Department of Economy, Science and Innovation of the Flemish Government. For example, many health claims ascribed to food products targeting the microbiome lack sufficient scientific substantiation and are merely associative, with no established causal pathway. For such a promising scientific field to lead to innovative applications, policies on science and innovation could be improved in several areas: (1) international research should be strengthened, with common access to a large interconnected data infrastructure; (2) standard protocols are required for clinical design and marker validation, as better characterisation of a healthy gut will be important for establishing disease biomarkers; (3) public-private collaboration could be reinforced; (4) the framework for evaluating health claims for new food products and new dietary approaches needs to be improved. Finally, (5) healthcare professionals and the public should be informed in a clearer and more understandable way.

In his closing remarks, Othmar Karas, Vice-President of the European Parliament (PPE, Austria) and STOA Panel member, noted how microbiomes dominate every aspect of our lives. Studying microbiomes and their effects opens a range of new possibilities in medicine, agriculture, the circular economy, waste decomposition, recycling, and sustainable energy generation. The last few years have seen a number of tools put forward such as the circular economy action plan, the Farm to Fork Strategy, and the EU4Health programme. Nevertheless, he concluded, a lack of EU regulation persists around microbiomes and these gaps must be filled: ‘Now we need to act’.

The full recording of the workshop is available here.

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