Online now a multicenter Crohn's Disease study of South Asian patients that explores environmental impacts on #CD, linking geography and immigrant status with disease presentation and serologic markers.

linkinghub.elsevier.com/retrieve/pii...

#crohnsdisease

<em>Immunology & Cell Biology</em> | ASI Journal | Wiley Online Library In this article, we have analyzed the serum proteome and metabolome in inflammatory bowel disease patients being treated with the anti-α4β7 integrin therapeutic agent vedolizumab. The pretreatment bi...

Check out our recent work with John Rioux and the iGenoMed Consortium! Serum proteomic and metabolomic profiling in #IBD patients initiating vedolizumab identified pro-inflammatory analytes associated with treatment response.

onlinelibrary.wiley.com/doi/10.1111/...

Eggerthella lenta Produces a Cryptic Pro-inflammatory Lipid Eggerthella lenta is both one of the most studied and least understood members of the human gut microbiome. Most of the interest in this Gram-positive anaerobe originates from multiple robust associations of its population with a variety of autoimmune diseases, perhaps most notably inflammatory bowel disease (IBD). The links between bacteria and inflammation are only partially known. Inflammation is driven by Th17 cells and their inflammatory cytokine IL-17, and the population of these cells is promoted by a transcription factor, RORγt. Bacterial metabolites appear to activate RORγt in a cell- and antigen-independent fashion, but the metabolites and their activating mechanism are unknown. This report describes an assay-driven search for pro-inflammatory metabolites from E. lenta that revealed a plasmalogen-triggered plasmalogen pair that forms a single molecule signal transduction device. Small electrophiles characteristic of inflammatory environments react with the plasmalogen’s sensitive vinyl ether moiety to create a lipid signal, a lysoglycoglycerolipid that upregulates the inflammatory cytokines TNF-α and IL-6 through a TLR receptor. This provides a molecular mechanism that allows E. lenta to upregulate inflammatory responses in a cell- and antigen-independent fashion. This molecular mechanism is similar to an endogenous signaling system that upregulates RORγt through a triggered mammalian plasmalogen signal, 1–18:0-lysophosphatidylethanolamine.

This finding suggests that molecular patterns could be more useful categories for microbiome-driven immune regulation than taxonomy. (2/2)

Read the study in JACS – pubs.acs.org/doi/10.1021/...

@broadinstitute.org
@mgbresearch.bsky.social

In our latest collab w/the Clardy Lab
@HarvardMed to mine microbial metabolites for immunomodulators, we identified how Eggerthella lent—one of the most studied & least understood members of the human gut microbiome—upregulates inflammatory responses in a cell- & antigen- independent fashion. (1/2)

...and maps expression of genetic risk variants onto intestinal biogeography. Read the results of this exciting collaboration!

@broadinstitute.org @mgbresearch.bsky.social @genelayinstitute.bsky.social

Single-cell and spatial transcriptomics of stricturing Crohn’s disease highlights a fibrosis-associated network - Nature Genetics Single-cell and spatial transcriptomics analysis of stricturing Crohn’s disease highlights cellular heterogeneity in fibrotic tissue and identifies neighborhoods of fibroblasts and immune cells contri...

Very excited to share our latest work in @NatureGenet with the Smillie lab: a spatial transcriptomics atlas of stricturing #Crohns disease that offers new insights into mechanisms driving fibrotic complications in chronic gut inflammation...(cont.)
www.nature.com/articles/s41...

@broadinstitute.org @mgbresearch.bsky.social @genelayinstitute.bsky.social

(6/6)

(5/6) This suggests that OMV-like nanoparticles could one day be used to deliver vaccines or therapeutics to immune cells! We’re thrilled to have this paper out in the world. Congratulations to co-first authors Eric Brown and Emily Temple on this important work!

(4/6) These findings are exciting for a few reasons. Not only do they clarify the mechanism of a microbiome-host interaction that is important in inflammatory disease, they add to the mounting evidence that OMVs can be an effective vehicle for immunomodulatory signaling.

(3/6) We found that OMVs secreted by Bacteroides deliver sphingolipids into host immune cells, activating mevalonate (cholesterol biosynthesis) pathway genes and increasing anti-inflammatory IL-10 secretion. The IL-10 response is dependent upon the mevalonate pathway activation.

(2/6) Bacteroides species are ubiquitous in the human gut microbiome. Unlike most bacteria, their membranes contain sphingolipids (SLs), whose abundance in the gut negatively correlates with inflammation. We wanted to understand the role of SLs in microbiome-host interactions.

(1/6) Our latest paper in ‪@cp-cellhostmicrobe.bsky.social‬ shows that sphingolipids in Bacteroides outer membrane vesicles (OMVs) induce a tolerogenic host cell response through the cholesterol biosynthesis pathway.
www.cell.com/cell-host-mi...

Bacterial sphingolipids delivered by outer membrane vesicles persist within mammalian immune cells and promote IL-10 secretion via the mevalonate pathway
www.cell.com/cell-host-mi...
@thexavierlab.bsky.social @cp-cellhostmicrobe.bsky.social

Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense Enteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is conside...

🚨New paper with @thexavierlab.bsky.social @science.org on the critical role of 🔄neuroimmune crosstalk in immune defense in the gut🪱🪱.
🧪@genelayinstitute.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social @broadinstitute.org
www.science.org/doi/10.1126/...

Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense Enteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is conside...

Out now in @Science! We and the @kuchroolab.bsky.social described responses of enteric neurons to inflammatory cues during infection, showing that primary sensory neurons detect type 2 cytokines, balance neuropeptides, and influence site-specific immunity

www.science.org/doi/10.1126/...

Our entire lab is so proud of you all and we are looking forward to watching your careers in health and life sciences continue to grow!

And last but not least: Joel Adade, a dedicated RA in the Klarman Cell Observatory, is joining the @umasschan.bsky.social UMass Chan School of Medicine MD program so that he can pursue his dreams of providing health care for underserved populations in his community.

Next up: Rebecca Cohen, one of our outstanding clinical research coordinators, will join the @jhu.edu Johns Hopskins ScM program in Molecular Microbiology & Immunology!

Dedicating our first Bluesky post to our junior scientists moving on to next exciting steps of their career!

First on our list: huge congrats to Joanna Atwater, one of our amazing clinical research coordinators, on her next big step - pursuing a DMD at @tufts.edu Tufts School of Dental Medicine!