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Genetically modified microorganisms for health

Episode 21: Genetically modified microorganisms for health

Genetically modified microorganisms for health

 

The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Genetically modified microorganisms for health, with Dr. Carlos Gómez-Gallego

Episode summary:

In this episode, ISAPP podcast host Dan Tancredi joins guest Carlos Gómez-Gallego PhD, from University of Eastern Finland, to discuss genetically modified microorganisms. They go over what genetically modified microorganisms are, their potential benefits over non-modified microorganisms, and how they might improve human health–in particular, diseases of the metabolic and immune systems.

 

Key topics from this episode:

  • Genetically modified microorganisms are those that have been modified using genetic engineering, giving them abilities they do not normally have. Functions can be either conferred or deleted. Different genetic engineering tools can be used – e.g. to make them produce therapeutic compounds, or make them increase degradation of toxins or harmful compounds.
  • One advantage over non-modified microorganisms is the potential to have continuous delivery of a therapeutic compound, and the potential to deliver it to a localized area in order to avoid unwanted interactions.
  • Genetically modified microorganisms have promise in metabolic and immune-linked disorders such as non-alcoholic fatty liver disease (NAFLD).
  • In NAFLD, genetically modified E. coli Nissle can secrete hormones that are under-regulated or under-expressed. His group modified bacteria by introducing a plasmid that allowed it to produce aldafermin, an analog of the human hormone fibroblast growth factor 19 (FGF19).
  • With genetically engineered microorganisms, we must consider the benefits but also the risks. However, if it’s a therapeutic for a disease with few or no alternatives, there’s a strong case for developing them.
  • To increase efficacy and safety of these microorganisms, it’s possible to introduce sensors that produce the therapeutic in response to different stimuli. Also, it’s important to modify the bacteria so their use is controlled and they cannot spread. They can also be modified to avoid transmission of genes.
  • Are there market-approved genetically modified microorganisms? No approved ones yet, but some are in Phase 1 and Phase 2 clinical trials.

Episode links:

About Dr. Carlos Gómez-Gallego:

I am a Senior Researcher at the Institute of Public Health and Clinical Nutrition (University of Eastern Finland). I have completed two university degrees, one in Biology and another in Food Science and Technology, and an MSc in Nutrition and Health. I subsequently completed a Ph.D. from the University of Murcia, where I investigated the effect of infant formula processing on the content of polyamines and bioactive peptides, and their impact on intestinal microbiota and immune system development during lactation.

My research and interests are primarily focused on advancing the understanding of the impact of diet, food, and bioactive compounds on human microbiota and their association with human health. As part of the BestTreat project (https://besttreat.eu/index.html), I have co-supervised two PhD students (Johnson Lok and Valeria Ianone) who evaluated the potential use of engineered E. coli Nissle 1917 producing human hormones for the treatment of non-alcoholic fatty liver disease (NAFLD) in a mouse model. The first publication has already been submitted, and the second is currently in process.

More info about my publications:
Research Gate https://www.researchgate.net/profile/Carlos-Gomez-Gallego
UEF connect https://uefconnect.uef.fi/en/person/carlos.gomez-gallego/#information

The future is microbial: A post-pandemic focus on identifying microbes and metabolites that support health

By Prof. Maria Marco, Department of Food Science and Technology, University of California Davis, USA

The COVID-19 pandemic has been a sobering reminder of the significance that microorganisms have on human life. Despite the tremendous scientific and medical advances of the twentieth century, our best precautions against the virus have been to practice the oldest and most simplistic of all public health measures such as washing hands and maintaining physical distance from others. At the same time, the effectiveness of the new SARS-CoV-2 vaccines and the speed in which they were developed show how sophisticated and advanced our understanding of viruses has become. Taken together, the limitations and successes of responses to the pandemic underscore the power of investment in microbiology research. This research, which was first catalyzed by the pioneering work of Louis Pasteur, Robert Koch, and contemporaries in the late 1800s, was the basis for the overall reduction in infectious diseases during the twentieth century. Continued investment in these efforts will prepare us for the next pandemic threat.

Beyond pathogens to health-promoting microbes

As our attention turns to the promise of the New Year, we may also take this moment to appreciate the fact that microorganisms can also do good. Our “microbial friends” were first promoted by the lauded biologists Élie Metchnikoff, Henry Tissier, and Issac Kendall at the turn of the twentieth century. Since then, nearly another century passed before the power of microorganisms to benefit human health reached wider acceptance.

Marked by the emergence of laboratory culture-independent, nucleic-acid based methods to study microbial communities, there is now excitement in the identification of microorganisms that are important for health promotion. This interest is catalyzed by the urgency to find ways to prevent and treat cardiovascular diseases, cancers, and other non-communicable, chronic conditions that are now the leading causes of death worldwide. Much like the pressure to address infectious diseases as the primary cause of mortality prior to the twentieth century, so too is the need today for sustained research investments in studying how certain microorganisms contribute to, or may be essential for, preventing and treating the greatest threats to public health in the modern era.

Exemplified by the growing number of human microbiome studies, it is now broadly understood that the human microbiome contributes positively to digestive, immune, and endocrine systems function. Systematic reviews and meta-analyses of clinical trials support the use of probiotics for a variety of conditions and there are positive associations between the consumption of fermented dairy foods and good metabolic health. To understand how microbes can be beneficial, numerous mechanisms have been proposed (for example, modulation of the immune system and production of neurochemicals that can impact the gut-brain axis), and these mechanisms apply to both autochthonous microbiota and probiotics alike. However, our understanding of exactly how this occurs lags far behind what is currently known about microorganisms that cause harm.

Identifying microbes & metabolites that maintain health

The future of beneficial microbes is in identifying the specific, health-promoting metabolites, proteins, and other compounds that they make. Presently only a handful of such examples are known. Perhaps most recognized are the short chain fatty acids, butyrate, propionate, and acetate, which are known to bind specific human cell receptors to modulate numerous cell pathways including those that affect metabolism. Other microbial compounds generated as intermediate or end products of microbial metabolism (such as metabolites of amino acids), secondary metabolites (such as bacteriocins), and bacterial cell surface constituents (such as certain membrane proteins) were shown to benefit health, although a more complete description of mechanistic details for their effects remains to be discovered. Precise mechanistic descriptions of “beneficial factors”, or the microbial enzymatic pathways and molecules that induce desired cellular and systemic responses in the human body, will be pivotal for elucidation of the precise ways microorganisms sustain health and well-being (for more detail on this topic see here).

Based on what we know about the complexity of the human microbiome and the now many decades of probiotics research, this effort will require innovation and multi-disciplinary coordination. Just as early microbiologists raced to address the high rates of mortality due to microbial pathogens, we are in a new age where again microorganisms are regarded as emerging public health threats. However, we now have to our advantage the knowledge that not all microorganisms cause harm but instead the majority may offer solutions to the greatest health challenges of the twenty-first century.