Highlights of Gut Microbiota for Health - World Summit 2023

Gut microbiota research is now developing complex clinical applications such as faecal microbiota transplantation (FMT), next-generation probiotics derived from the human microbiota, medicines developed from microbial products (postbiotics) and also diets based on our current knowledge of host/microbiota interactions. The challenges and issues raised by the arrival in clinical practice of these new forms of medicines today bring up a large number of regulatory, ethical and scientific questions which were developed throughout the congress. At the opening of the symposium, Professor Eugène B. Chang (Chicago, USA) introduced the challenges and new concepts involved in the development of this new type of medicine. Some of these include: the pressing need to establish a specific regulatory framework and design industrial standards capable of underpinning the development of new probiotics; and the need to understand treatments targeting the microbiota in an ecological and dynamic manner, i.e. evolving products that fit into an ecological niche which, in turn, they help to modify.

New pre- and probiotics to boost anti-tumour immune response

We have known about the important role played by gut microbiota in modulating anti-tumour immune response for around 10 years; however, the underlying mechanisms are still poorly understood. During the first session of the congress, Dr. Michael Scharl (Zurich, Switzerland) and Professor Harry Sokol (Paris, France) presented their latest findings regarding the identification of microbiological and metabolic candidates for combination therapies with conventional treatments to stimulate anti-tumour immunity. Thus, by studying differences in tumour development in murine models from different animal houses, Dr. Scharl’s team identified four bacterial strains which, when administered alone, reduced tumour development in mice (Eubacterium hallii, Faecalibacterium prausnitzii, Roseburia intestinalis, Anaerostipes caccae) [1].

Interestingly, administration of the supernatant of these strains was sufficient to obtain a stimulatory effect on the anti-tumour immune response.

The metabolism of 3-OH dodecanoic acid has been identified as one of the mechanisms potentially responsible for this effect, paving the way to the development of specific postbiotics.

In line with these findings and the bacterial consortium identified, Professor Sokol presented unpublished work confirming the beneficial impact of Faecalibacterium prausnitzii in the response to immunotherapy.

In addition to the plenary scientific sessions, several workshops were organised to foster lively exchanges with the experts. Thus, the session on “Engineered microorganisms as therapeutic agents” explored the current advances and perspectives in the development of new genetically engineered microbiological therapeutic agents. During this session, Dr. Nicholas Arpaia (New York, USA) presented an engineered strain of Escherichia coli developed with a lysis cycle coordinated between the different bacteria via a quorum sensing mechanism resulting in the release of a nano-antibody (anti-CD47 antibody fragment) inhibiting an immune tolerance signal in phagocytes [2]. In mice, injection of these bacteria at the tumour graft site resulted in the complete elimination of implanted tumours by the immune system via phagocytosis stimulation but also through adaptive immunity recruitment, thus suggesting the generation of a sustained immune and anti-tumour response. However, the ethical and regulatory framework required to allow the clinical evaluation of this type of treatment has yet to be defined, and this point was specifically discussed during the remainder of the workshop.

Faecal microbiota transplantation, gaining a better understanding of mechanisms underpinning its effectiveness

Among microbiota-based therapies, FMT is currently the most widely evaluated treatment in clinical practice across many indications. Despite a large number of studies, the factors determining the effectiveness of FMT and its mechanism of action are not yet fully understood. The work presented by Dr. Gianluca Ianiro on the combined analysis of 226 FMTs provided new insights into understanding this therapy by showing that the beneficial effect of FMT was correlated to the engraftment capacity of donor strains in the recipient and that this could be enhanced by the prior administration of antibiotics to open up the intestinal ecological niche, along with the combination of several methods when administering FMT [3].

Foods preserving intestinal barrier integrity

Several presentations also explored the importance of dietary factors in maintaining the intestinal barrier integrity and its consequences on health. Especially a fibre-rich diet has been shown to prevent the degradatation by Akkermansia muciniphila of the mucus layer that protect the colonic epithelium (presentation of Dr. Mahesh S. Desai, Luxembourg). Conversely, some food additives can boost the penetration of bacteria in the mucous layer in contact with the epithelium and predispose to the development of inflammatory colitis (presentation of Dr. Benoit Chassaing, Paris, France) [4].

This better understanding of the mechanisms underpinning the efficacy of microbiota- targeted therapies and the complexity of their use in clinical practices illustrates the need for clinical experts able to develop and use microbiota-based applications in the routine care. Dr. Ianiro, a world expert in FMT suggested that such qualifications should be grouped together under the concept of «microbiome clinician ».

At this 11th congress, the GMFH symposiums, by creating a rich and accessible space for exchange between clinicians and researchers, contribute to the emergence of this type of expertise.