Sishen Wan modulates gut microbiota and short-chain fatty acids in a murine chronic sleep deprivation model
In a murine chronic sleep deprivation model, high-dose Sishen Wan favored behavioral, inflammatory, and microbiota outcomes compared to the model group, with no evidence of efficacy in humans.
| Population | Male C57BL/6J mice subjected to chronic sleep deprivation via modified multiple-platform method |
|---|---|
| Intervention | Sishen Wan at three oral doses (low, medium, high — SSW-H); fluoxetine as active comparator |
| Comparator | Model group (sleep-deprived, untreated) and control group (no deprivation) |
| Outcome | Sucrose preference (anhedonic behavior); Immobility in tail-suspension and forced-swim tests; Pro-inflammatory serum/tissue cytokines; Fecal SCFAs (acetate, propionate, butyrate); Gut microbiota composition (diversity and richness); Colonic and hippocampal histopathology; Phenotypic transfer via FMT (behavior and histology in recipients) |
Summary of findings
| Outcome | Effect | 95% CI | Certainty | Clinical relevance | Notes |
|---|---|---|---|---|---|
| Sucrose preference (anhedonic behavior) | Direction: SSW-H vs Model favored; in the SMD or 95% CI reported | — | Very low | — | 1 studies |
| Immobility in tail-suspension and forced-swim tests | Direction: SSW-H reduced immobility vs Model; in the SMD or 95% CI reported | — | Very low | — | 1 studies |
| Pro-inflammatory serum/tissue cytokines | Direction: SSW-H reduced vs Model; in the MD or 95% CI reported | — | Very low | — | 1 studies |
| Fecal SCFAs (acetate, propionate, butyrate) | Direction: SSW-H increased vs Model; in the MD or 95% CI reported | — | Very low | — | 1 studies |
| Gut microbiota composition (diversity and richness) | Direction: SSW-H shifted toward Control profile, increased Akkermansia; in the alpha-diversity index or 95% CI reported | — | Very low | — | 1 studies |
| Colonic and hippocampal histopathology | Direction: SSW-H attenuated injury vs Model; in the quantitative effect size reported | — | Very low | — | 1 studies |
| Phenotypic transfer via FMT (behavior and histology in recipients) | Direction: SSW-H donor FMT milder behavioral and histological changes vs Model donor FMT; in the quantitative effect size reported | — | Very low | — | 1 studies |
Context
Chronic sleep deprivation associates with gut dysbiosis, neuroinflammation, and depression-like behavior in animal models. Sishen Wan is a traditional Chinese herbal formula with clinical use in chronic diarrhea and documented effects in colitis models. Its action on the gut-brain axis during sleep deprivation had not been systematically investigated.
What the study showed
Chronic sleep deprivation reduced sucrose preference and open-field activity, prolonged immobility in tail-suspension and forced-swim tests, and elevated pro-inflammatory cytokines. SSW-H partially reversed these parameters and increased fecal acetate, propionate, and butyrate, as well as serum acetate. FMT from SSW-H donors attenuated behavioral and histological alterations in recipients, while FMT from model donors reproduced deprivation phenotypes. Absolute numbers and 95% CIs were not reported in the available text for most outcomes.
How it was done
Preclinical experimental study in male C57BL/6J mice; sleep deprivation by modified multiple-platform method; treatment groups with three SSW doses and fluoxetine; cross-group FMT; assessment by 16S rRNA (microbiota), chromatography (SCFAs), untargeted serum metabolomics, hippocampal transcriptomics, RT-qPCR, and resting-state fMRI. Duration of deprivation and treatment not precisely specified in the available abstract.
Effect magnitude
Effects expressed descriptively and as between-group comparisons; the available text does not report standardized effect sizes (SMD, RR, OR) or 95% CIs for primary outcomes. Clinical magnitude is not extrapolable to humans.
Risk of bias
Exclusively preclinical study in male mice; no formal risk-of-bias tool applied (SYRCLE or ARRIVE 2.0 not mentioned). Absence of absolute numbers and 95% CIs for behavioral outcomes. Multiple-platform sleep deprivation model introduces physical stress confounders. Human-equivalent dose and treatment duration not established.
What this study does NOT prove
This study does not prove efficacy of Sishen Wan in humans with sleep deprivation, mood disorders, or microbiota alterations. It does not establish causality between SCFA modulation and behavioral improvement.
In clinical practice
There is no basis for clinical recommendation of Sishen Wan for sleep deprivation or gut-brain axis disorders in humans based on this study. Clinicians should treat this data as hypothesis-generating for future clinical trials. Fluoxetine was used as an experimental reference only, not as a validated clinical comparator in this context.
Limitations
Exclusively preclinical study in male mice; no formal risk-of-bias tool applied (SYRCLE or ARRIVE 2.0 not mentioned). Absence of absolute numbers and 95% CIs for behavioral outcomes. Multiple-platform sleep deprivation model introduces physical stress confounders. Human-equivalent dose and treatment duration not established.
What is still missing
Randomized controlled clinical trials in humans with sleep deprivation and standardization of the SSW formulation are needed before any clinical application. Causal mechanisms linking SCFA modulation to behavioral outcomes require isolation.
Technical appendix
Version history
- 1.0 · 2026-10-12 — Auto-generated under Evidence Standard v1.0