Fueling a gut fire

This 2022 article commented on a human / rodent study of gut dysbiosis:

“Crohn’s disease (CD) is a chronic disease that causes inflammation in the gastrointestinal track. Together with ulcerative colitis, another major type of inflammatory bowel disease (IBD), these intestinal disorders affect millions of people in the U.S. and worldwide.

Excessive T helper 1 (Th1) and Th17 cell responses have been documented to act as important mediators of CD pathogenesis. An imbalance between regulatory T (Treg) cells and effector T cells in the intestinal tissue microenvironment is crucial to promote gut inflammation in CD.

Lysophosphatidylserine (LysoPS) exaggerates intestinal inflammation by fueling IFNγ-producing Th1 cells via metabolic reprogramming and chromatin modification (panel A). While this work has provided novel functional insights into dysbiotic microbiota–derived LysoPS in CD pathogenesis (panel B), it also raises several questions. 

m_jem_20220723_fig2

By employing multiple animal colitis models, the authors have shown that administration of LysoPS was detrimental in T cell–driven colitis, while having no significant impact on pathogenesis of T cell–independent dextran sodium sulfate–induced colitis.

Considering the complex nature of LysoPS in regulating responses of different immune cell types in a given tissue environment under a particular physiological or pathological condition, more research is needed to elucidate the precise role of LysoPS in CD before targeting these multifunctional bioactive lipids to treat human gastrointestinal disorders becomes a reality.”

https://doi.org/10.1084/jem.20220723 “Fueling the fire in the gut”


The referenced study:

  • “We identified key metabolites derived from dysbiotic microbiota that induce enhanced Th1 responses and exaggerate colitis in mouse models.
  • Patients with CD showed elevated LysoPS concentration in their feces, accompanied by a higher relative abundance of microbiota possessing a gene encoding the phospholipid-hydrolyzing enzyme phospholipase A.
  • Our findings elaborate on the mechanism by which metabolites elevated in patients with CD harboring dysbiotic microbiota promote Th1-mediated intestinal pathology.”

https://doi.org/10.1084/jem.20211291 “Lysophosphatidylserines derived from microbiota in Crohn’s disease elicit pathological Th1 response”


When standard DSS and TNBS models of colitis don’t account for observed effects, other avenues need to be investigated. Relationships with our gut microbiota are complicated.

PXL_20220529_183842508

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