Click on the discussion groups below to see full descriptions.
Discussion Group 1: Characterization and quantification of postbiotics
Chairs: Gabriel Vinderola PhD, National University of Litoral, Argentina and Seppo Salminen PhD, University of Turku, Finland
Postbiotics are defined in the ISAPP consensus definition as ‘a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host’. Subsequent to the release of this definition, questions have been raised about how to quantify postbiotics according to this definition, and that clarification of the approach to active components and their measurement is required for implementation in scientific and regulatory circles.
It is clear that characterization of postbiotic products may be challenging, especially with increased complexity that arises by use of multiple inanimate strains, inclusion of metabolic end-products, and the presence of whole and fragmented cells. In this sense, there is some uncertainty among stakeholders about postbiotics and how to implement the consensus definition. There is a need to clarify how to quantify postbiotics. The aim of this Discussion Group is to convene academic experts and industry scientists to discuss specific key issues about production, characterization, quantification and stability of postbiotics for practical and regulatory purposes, to produce a technical paper providing examples about how some postbiotic products are produced/characterized/quantified commercially and make some general recommendations about how to quantify postbiotics. We aim to discuss postbiotics ranging from “simple products” (just an inanimate single strain) to more complex formulations (a mixture of inanimate strains or cell fragments, plus metabolites); how processes are controlled to allow reproducibility; and to propose methodologic tools to characterize and quantify postbiotics, either at a single timepoint or over the duration of shelf life.
Discussion Group 2: How can we establish causal mediation in microbiome intervention studies?
Chairs: Daniel Tancredi PhD, University of California, Davis, United States and Kristin Verbeke PhD, Katholieke Universiteit Leuven, Belgium
Many intervention studies targeting the microbiome have associated eventual changes in microbial composition or function to changes in a particular health outcome. Such associations do not necessarily establish that the microbiome change that was caused by the intervention was itself the cause of the eventual effect on the particular health outcome, because one has to be able to rule out confounding, reverse causality, and reporting bias as potential alternative explanations. Although randomization of a potential cause is a powerful technique for controlling for confounding of a simple cause/effect relationship, randomizing the upstream intervention does not by itself eliminate confounding of downstream cause-effect linkages.
Hence, demonstrating causal mediation is difficult and requires clever experimental design and analysis strategies to chain together two or more cause/effect relationships. In the context of microbiome intervention studies, the level of difficulty can be even more severe, due to the microbiome measurements potentially being high-dimensional and/or compositional. Additionally, absent the possibility of randomizing both the intervention and the microbiome manipulation, ruling out all potential confounders may require deeper systems knowledge of the microbiome than is currently available. Nevertheless, the establishment of causal mediation is important to advance the field and, potentially, to support health claims involving mediation, including those involving whether an intervention fulfills the definition of a prebiotic.
In this discussion group, we will discuss recent progress and remaining research gaps for causal mediation studies involving the microbiome. Our goal is to understand how to improve the quality of the evidence for a claimed mechanistic linkage involving the microbiome as a mediator of health effects caused by a biotic intervention. We will discuss experimental designs and analysis strategies aimed at causal mediation that can be adapted for use in microbiome intervention studies. We will consider how the overall evidence for a mediated causal linkage might be enhanced by experimental and observational studies involving animal models, genetic epidemiology, and systems biology.
Discussion Group 3: The microbiome and neurodegenerative and neurodevelopmental disorders
Chairs: Eamonn Quigley MD, The Methodist Hospital and Weill Cornell School of Medicine, Texas, USA and Hania Szajewska MD, PhD, The Medical University of Warsaw, Poland
This workshop will address a very topical area – microbiome-CNS interactions – with the aim to explore how insights from microbiome research can be translated into clinical strategies for managing neuropsychiatric or neurodegenerative diseases. Topics for discussion will include advances in our understanding of the role of the microbiome in the development of the central nervous system and the intriguing issue of how the microbiome communicates with the CNS. We will explore how these microbiome-gut-brain connections/interactions impact on the human brain, as well as how interventions that modulate the microbiome can ameliorate neurodegenerative and neurodevelopmental disorders and related symptoms, such as altered mood.
The session will focus on bridging the gap between research and practice, investigating the application of microbiome study findings in real-world clinical settings to improve the management and treatment of these diseases. Relatively common disorders such as autism and Parkinson’s disease will serve as examples of how microbiome-CNS interactions are being explored and insights gained.
Discussion Group 4: Evidence for candidate prebiotics, including polyphenols, resistant starch, and animal-derived substances.
Chairs: Karen Scott PhD, University of Aberdeen, Scotland and Kelly Swanson PhD, University of Illinois at Urbana-Champaign, Illinois, USA
The number of substances widely known in the prebiotic category has not changed greatly since the launch of prebiotics in 1995, namely FOS, inulin, and GOS. This is despite many publications describing the impact of a variety of different substances on the gut microbiota and subsequently on health, hence potentially acting as prebiotics. This discussion group will investigate the reasons behind this and explore what is required for this list to be expanded to include additional substances with described beneficial effects on health, mediated via the microbiota. We will discuss the existing evidence for specific ‘candidate’ prebiotics and establish how they fit the criteria and thus may move from candidate to accepted prebiotics, within the guidelines of the current definition. We will also try and outline a usable infographic outlining this descriptive process.
Discussion Group 5: How does digestion affect prebiotic and probiotic function?
Chairs: Anisha Wijeyesekera PhD, University of Reading, United Kingdom and Maria Marco PhD, University of California, Davis, USA
Recent advances have revealed fascinating insights into digestive processes and the mechanisms through which ‘biotics exert their effects. The further elucidation of some of these complex mechanisms (for example, physical and chemical (acid/bile) digestive processes) and the impact they have on diet and dietary substrates provide a step change in our understanding of the effects of digestion on ‘biotics function. Other recent advances include the development of analytical approaches to uncover structural and functional characteristics of the intestinal environment and gut microbiota that may be exploited for personalised medicine. This includes technological innovation in the areas of ingestible in situ sampling and delivery devices for collection of novel spatial and temporal data from the gut environment. By better understanding gastrointestinal digestive physiology and inter-individual variations will pave the way to detect, monitor, treat and ultimately improve health outcomes.
These innovative analytical advances demonstrate huge potential for enhancing the viability and efficacy of ‘biotics. This discussion group will review the latest science in this area, and discuss, debate and conclude on how digestion affects prebiotic and probiotic function, and recommendations of future research priorities.
Discussion Group 6: Next-generation probiotics by implementation of genetic engineering and other tools
Chair: Sarah Lebeer PhD, University of Antwerp, Belgium, Colin Hill PhD, DSc, University College Cork, Ireland
During the last two decades, the diversity of microbial strains and species that are being explored as probiotics is steadily increasing. At the same time, the genetic tools to precisely genome engineer and improve the functionality of specific microbial strains and whole communities are rapidly advancing. However, such next-generation probiotics and tools will not be rapidly followed by the necessary regulatory updates to allow market entry of these novel approaches.
In this discussion group, the following aspects will be discussed.
- What are potential benefits and pitfalls of such next-generation probiotics?
- Is the probiotic field waiting for such innovations? For which conditions and problems?
- Will genetically modified probiotics only have potential in the medical field but not in food and food supplements?
- What are the functional targets for GMO modifications – how to determine particular microbial functions/traits to optimise for, what factors should be considered?
- Considering single microbe design vs ecosystem/consortia design
- Engineering safety – beyond single microbe traits, considering safety in the ecosystem and foreseeing unintended effects