Beyond Gut Bacteria: Transkingdom Interactions Underlying GI Diseases

In a lectures-session of MMT, invited scientists introduced their interest in the microbiome world beyond bacteria.

Iliyan Iliev, from Weill Cornell Medicine, talked all about gut mycobiome in inflammatory bowel disease (IBD). Mucosal washings during colonoscopy allowed Iliev lab to isolate distinct strains and explore their potential in the development and management of IBD. With a strong consensus in the room, he proved to explain why and how strains are the Way-to-Go not only in microbiome but mycobiome research as well!


Andrew Hryckowian, Assistant Professor of Medicine, Medical Microbiology and Immunology at the University of Wisconsin, focused on bacteriophage susceptibility and resistance. Considering the burgeoning antibiotic crisis, the talk gathered a lot of attention. Andrew Hryckowian suggested that we still do not know “What bacteria phages infect”. The aim of his young lab is to explore how bacteria are “trained” to resist not only antibiotics, but phages as well. He introduced the predominantly physician oriented audience attending the DDW meeting to the unique single-bacterium symbiosis model of the Hawaiian Squid. This binary association, a partnership between the Hawaiian bobtail squid, Euprymna scolopes, and the luminous bacterium Vibrio fischeri, has offered a window into one area of interest: the colonization of animal epithelia by bacterial partners. In collaboration with the Squid Vibrio Labs, led by Margaret McFall-Ngai and Ned Ruby, Hryckowian lab aims to answer the critical question of bacteriophage resistance.


Aryl Hydrocarbon Receptor in Gastrointestinal Diseases

Of note was the focus of the next lectures-session on the role of Aryl Hydrocarbon Receptor (AhR) in Gastrointestinal Diseases. Diet-microbiota interactions have been shown to play a key role in human health and disease. Over the past decades, research has emerged demonstrating that the capacity of the commensal microbiome to metabolize nutrients into bioactive components that influence human physiology an immunity. In intestinal inflammatory conditions such as IBD and celiac disease, this key function of the gut microbiota is altered, leading to impaired activation of AhR which plays a role in the alteration of the intestinal barrier and the inflammatory process. MMT in this translational symposium stressed the current need in the field to understand the molecular sensors of such metabolized components, such as the nuclear aryl hydrocarbon receptor or AhR.

Bruno Sovran from the Amsterdam University Medical Centers, The Netherlands, provided insight into the role of gut microbiota-derived tryptophan metabolites in the development of neonatal intestinal failure. He showed that preterm neonates depict altered capability to produce microbial-derived tryptophan metabolites, such as indole lactate (ILA). ILA was shown to prevent epithelial inflammation and promote intestinal barrier function in human intestinal organoids. Altered tryptophan metabolite levels were also observed in blood and feces prior to neonatal sepsis suggesting a role of tryptophan metabolism in sepsis pathogenesis. Sovran showed that human milk contains beneficial tryptophan metabolites that can prevent cytokine-induced inflammation and intestinal barrier loss. Overall, these data suggested a possible beneficial mechanism of maternal milk to prevent neonatal intestinal failure.


The session also featured a talk on the role of microbiota derived AhR ligands in celiac disease, by Elena Verdu, from McMaster University. She presented compelling data showing that the microbial metabolism of tryptophan and production of indoles are impaired in patients with active celiac disease, a common autoimmune enteropathy triggered by ingestion of gluten in genetically susceptible people. She presented work on a genetically predisposed animal model where tryptophan and probiotics rescued the AhR pathway. Finally, trials in humans using tryptophan supplementation as a prebiotic are being conducted to investigate potential therapeutic potential in celiac disease. Overall, the data supports the notion that specific microbial therapeutics could be used to rescue AhR activation in the duodenum to prevent or accelerate healing in celiac disease. We look forward to seeing the results of these trial in a future DDW!

Harry Sokol, from the Saint-Antoine Hospital in Paris, presented data related to bacteria isolated from the human gut that exhibit a strong ability to activate AhR with protective effects in colitis models, representing a promising therapeutic avenue in IBD. Besides the alteration of microbiota tryptophan metabolisms, Sokol’s group also showed that host tryptophan metabolism and notably the kynurenine pathway is strongly impaired in IBD. The investigators identified metabolites from this pathway that can activate AhR. Finally, they showed that rewiring tryptophan metabolism using a recombinant enzyme to favor the endogenous production of anti-inflammatory metabolites is effective in colitis models, representing another attractive therapeutic strategy.


MMT Mentor Award

Among the very last symposia, the “AGA Diet-Driven Gut Microbiome Dynamics, metabolism and Extinction” got the room full-house! Chaired by Suzanne Devkota and Purna Kashyap, in this translational symposium, Justin Sonnenburg was rewarded with the MMT section mentor award, showcasing how focused, structured and supportive mentorship can benefit all team members to succeed in science, and work-life balance. Mentees of the Sonnenburg lab put together their thoughts and wishes in a short video that was presented during the session; they shared their enthusiasm and gratitude towards him. Carolina Tropini and Dylan Dodd who are currently leading independent programs introduced their research lines focusing on the intersection of diet-microbe-host physiology. A positive and inspiring note for all of us in Gut Microbiota for Health to take home and to keep team building!



Li X.V., Leonardi I., Putzel G.G., Semon A., Fiers W.D., et al. Immune regulation by fungal strain diversity in inflammatory bowel disease Nature 2022 doi: 10.1038/s41586-022-04502-w

Valles-Colomer M., Blanco-Míguez A., MAnghi P., Asnicar F., The person-to-person transmission landscape of the gut and oral microbiomes Nature 2023

McFall-Ngai M. Divining the essence of symbiosis: insights from the squid-vibrio model PLoS Biol 2014 doi: 10.1371/journal.pbio.1001783.

Lynch J.B., Bennett B.D., Merrill B.D., Ruby E.G., et al. Independent host- and bacterium-based determinants protect a model symbiosis from phage predation Cell Rep 2022 doi: 10.1016/ j.celrep.2022.110376.

Lamas B., Natividad J.M., Sokol H. Aryl hydrocarbon receptor and intestinal immunity Mucosal Immunol 2018 doi: 10.1038/s41385-018-0019-2.