ReviewNaunyn-Schmiedeberg's archives of pharmacology2026
Duloxetine as a gut-brain axis modulator in irritable bowel syndrome: neuroimmune, microbiota, and pharmacogenomic perspectives.
Review in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To provide an updated and integrative evaluation of duloxetine as a potential therapeutic agent for irritable bowel syndrome (IBS), with emphasis on its mechanisms of action across the gut-brain axis. The review addresses the key research question: Can duloxetine, beyond its antidepressant effects, modulate neuroimmune, microbial, and pharmacogenomic factors relevant to IBS, particularly pain-predominant subtypes? This narrative review provides a targeted synthesis of selected preclinical, clinical, and translational literature addressing duloxetine as a potential gut-brain axis modulator in irritable bowel syndrome. Evidence related to neuroimmune mechanisms, microbiota-related pathways, pharmacogenomic considerations, and clinical studies was narratively summarized. Evidence indicates that duloxetine modulates serotonergic and noradrenergic neurotransmission, decreases visceral hypersensitivity, and attenuates neuroinflammation via inhibition of microglial P2X4/NF-κB signaling. Duloxetine also shifts cytokine balance toward an anti-inflammatory profile (↑ IL-10, ↓ IL-6, ↓ TNF-α). Emerging data suggest additional benefits through modulation of gut microbiota composition, enhancement of short-chain fatty acid (SCFA) production, and improvement of intestinal barrier integrity. Pharmacogenomic factors, especially CYP2D6 and CYP1A2 polymorphisms, significantly influence duloxetine metabolism and therapeutic response. Compared with TCAs and SSRIs, duloxetine shows more favorable efficacy in relieving combined gastrointestinal and psychological symptoms with fewer sexual side effects. Duloxetine exhibits multifaceted actions that extend beyond mood regulation, positioning it as a promising but still investigational GBA-directed option dual-action therapy within the gut-brain axis framework. The collective findings support the need for biomarker-guided clinical trials incorporating microbiota profiling, cytokine signatures, and pharmacogenetic testing to validate duloxetine's role in precision-medicine-based IBS management.
Indexed as
Identifiers
42168405What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.