Butyrate promotes visceral hypersensitivity in IBS model via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.
Level 5 - mechanism / opinion, no new human data
Preclinical bench and animal study without human subjects.
PubMed 38953358 · doi:10.1128/mbio.01533-24
What was done
Researchers investigated gut-to-dorsal root ganglion (DRG) signaling pathways in an irritable bowel syndrome (IBS) rat model of visceral hypersensitivity (VH). Abdominal withdrawal reflex scores, fecal output, fecal water content, and total gastrointestinal transit time were measured across control rats, VH rats, sodium butyrate-treated rats, and VH rats treated with the probiotic VSL#3. In addition, fecal microbiota, short-chain fatty acids (including butyrate), colonic mast cell degranulation, and DRG expression of lincRNA-01028, miR-143, PKC, and TRPV1 were quantified. In vitro co-cultures of mast cells and DRG neurons were used to test the mechanism using butyrate and a lincRNA-01028 inhibitor.
What was found
The abstract reports no exact numerical values or effect sizes. Compared with controls, VH rats exhibited increased fecal water content, shortened transit time, higher abundance of *Clostridium sensu stricto 1*, elevated fecal butyrate, increased colonic mast cell degranulation, increased DRG expression of lincRNA-01028, PKC, and TRPV1, and reduced miR-143 expression. These changes were mirrored by butyrate treatment alone and reversed by VSL#3 probiotic treatment. In co-cultures, butyrate-treated mast cells increased DRG neuron TRPV1 current and expression of lincRNA-01028 and PKC while decreasing miR-143, which was reversed by a lincRNA-01028 inhibitor.
Why it matters
This work identifies a specific non-coding RNA signaling cascade (lincRNA-01028/miR-143/PKC/TRPV1) through which microbial butyrate and mast cells can promote sensory neuron sensitization in visceral pain models.
Limits
The study is entirely preclinical, using rodent models and in vitro co-cultures with no human validation. The abstract omits sample sizes, numeric values, and statistical error bounds. The finding that butyrate drives hypersensitivity contrasts with other literature showing protective, anti-inflammatory actions of short-chain fatty acids in the gut.
Cited by
- contradicts Short-chain fatty acids have anti-inflammatory effects and do not sensitize visceral pain nerves.