Highlights from the UEGW

Gut health

By Dr. Lucas Wauters
Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium

About this article

Created 17 January 2023

Updated 17 January 2023

After 2 years of virtual editions, the UEG Week 2022 was not only organized in-person (in Vienna) but also as the very first hybrid congress. With over 10,000 registrants (of which 19% virtual), it is the biggest European and “the best gastroenterology congress in the world” according to the organization and many others. Many highlights focused on the microbiome, of which a selection is discussed here.

A GLIMPSE AT THE HEALTHY MICROBIOME

Despite the timing on the last day, the high attendance of the popular session on “The microbiome as modulators of gut function” is easily explained by the selection of experts. Chaired by Pr. Harry Sokol (Paris, France) and Prof. Tim Vanuytsel (Leuven, Belgium), the first lecture by Pr. Jeroen Raes from the VIB Center for Microbiology (Leuven, Belgium) focused on the healthy gut microbiome. He stated that a definition of normal microbiota variation is essential to allow robust diagnostics, but that we do not even know what a healthy flora means. Indeed, only <10% of microbiota variation could be explained by host and environmental factors in the population- level analysis of the Flemish Gut Flora Project [1]. He showed that many of these variables replicated in the Dutch Microbiome Project, which recently confirmed the important effects of the environment and cohabitation [2].

In addition to the high between-individual variability, Pr. Raes showed evidence for substantial within-individual variation in the quantitative presence of microbial genera [3]. He explained that gut transit time was not only the primary confounder for microbiota composition but also the driver of temporal variation in healthy individuals. While the enterotypes (preferred community compositions) remained relatively stable, he richly illustrated the dysbiotic nature of the novel high-Bacteroides and low microbial load or B2-enterotype. Besides the diagnostic value of this marker across different diseases, he presented surprising findings of statins as a modulator of the microbiome. Finally, he stressed the need for more in vitro ecology work, as identification and isolation of species and their interactions is crucial to refine probiotic treatments and fecal microbiota transplantation (FMT).

FOCUS ON MICROBIAL STRAINS AND METABOLITES

As an alternative to in vitro work, Italian researchers presented improved strain-level metagenomics or the identification of subtypes of species in relation to FMT. As the first of many strong abstracts in the session on “Gut microbiome as pathogenic and therapeutic player”, the engraftment or strain sharing events within donors and recipients of FMT were nicely illustrated for different diseases. Interestingly, clinical success of FMT was associated with higher donor strain engraftment, which further improved with multiple routes of delivery and after antibiotics for infectious diseases [4]. Based on these findings, future donor-selection may not only optimize the microbiota composition but also the response after FMT, with specific protocols for different diseases.

During the main microbiome session, Pr. Nicolas Cenac (Toulouse, France) elaborated on the role of bacterial lipopeptides in irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders. Following evidence of analgesic properties of these metabolites, his group explored the link between stress-induced dysbiosis during pregnancy and the development of colonic visceral hyper- sensitivity (VHS), a hallmark of IBS. He nicely illustrated that prenatal stress induced IBS-like symptoms in mice, with a decrease in Ligilactobacillus murinus, which was associated with VHS. This also led to a lower production of lipopeptides containing γ-aminobutyric acid (GABA), with reversal of VHS after colonic administration in mice. Pr. Cenac explained how translation in humans was needed and confirmed by lower GABA-lipopeptides in feces of IBS-patients. The microbial metabolites are exciting new players in IBS and were fully published after the congress.[5]

MICROBIOME, MEDITERRANEAN DIET AND IMMUNOTHERAPY

Important abstracts of UEG Week covered the potential factors related to the success of immuno-therapy in melanoma, a type of skin cancer. Dr. Johannes R. Björk (Groningen, The Netherlands) presented changes in the gut microbiome in response to immunotherapy. As one of the Top Abstract awardees, he kicked off the second part of the opening session by showing evidence of baseline gut microbial biomarkers predictive of response. However, he explained that microbiota dynamics over the treatment course are still unexplored. Based on a multi-center cohort study, his longitudinal analysis of repeated stool sampling showed that species from the family Lachnospiraceae increased in responders, while species from the family Bacteroides increased in non-responders. Besides these novel potential targets (e.g., for FMT), the microbiota changes in those affected by immunotherapy-induced colitis may also provide diagnostic markers for the future. Interestingly, the increased butyrate producers in responders suggested a role of fiber degradation. Therefore, the same groups of researchers from the Netherlands and UK focused on the role of dietary intake in a separate analysis. They showed that patients who responded to immunotherapy were more likely to adhere to a Mediterranean diet, which is high in mono-unsaturated fatty acids, polyphenols, and fiber. In addition, immunerelated side effects were less likely with intake of whole grains or legumes and more likely with high red and processed meat. Future clinical trials will show whether this translates to treatment benefits for various tumor types, including gastrointestinal cancers.

In conclusion, important and novel findings on microbial strains, metabolites and the role of diet have advanced our understanding of the gut microbiome in disease, while taking important confounders (even in the healthy microbiome) into account.

Sources

^{1. Falony G, Joossens M, Vieira-Silva S, et al. Population-level analysis of gut microbiome variation. Science (80) 2016; 352: 560-4.

2. Gacesa R, Kurilshikov A, Vich Vila A, et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature 2022; 604: 732-9.

3. Vandeputte D, De Commer L, Tito RY, et al. Temporal variability in quantitative human gut microbiome profiles and implications for clinical research. Nat Commun 2021; 12.

4. Ianiro G, Punčochář M, Karcher N, et al. Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases. Nat Med 2022; 28.

5. Petitfils C, Maurel S, Payros G, et al. Identification of bacterial lipopeptides as key players in IBS. Gut 2022; Online ahead of print.}