Bacillus subtilis DE111 partially reverses endothelial dysfunction in western-diet fed mice.
- 2024-12-03
- Beneficial microbes 16(3)
- PubMed: 39631408
- DOI: 10.1163/18762891-bja00052
Study Design
- Type
- Clinical Trial
- Sample size
- n = 24
- Population
- Male C57BL/6J mice were fed a Western diet (WD; n = 24) or standard diet (SD; n = 24) for ten weeks to induce endothelial dysfunction
- Methods
- half of the animals in each group (n = 12) were allocated to receive B. subtilis DE111 (hereafter, PB) formulated into the diet for an additional eight weeks; outcomes included endothelial-dependent arterial dilation, glucose tolerance, body weight changes, microbiota profiles, and assessments of intestinal permeability and mucosal immunity markers
- Rigorous Journal
Imbalances in the gut microbiome have emerged as an important factor in endothelial dysfunction, a significant risk factor for cardiovascular disease. Thus, interventions targeting the microbiome may prove helpful in preventing or reversing this impairment. We previously reported that spore-forming Bacillus subtilis DE111 improved endothelial function in a cohort of healthy, non-obese humans after a four-week intervention. Building on these promising results, the present study sought to investigate whether administering B. subtilis DE111 could reverse endothelial dysfunction in mice with diet-induced obesity. Male C57BL/6J mice were fed a Western diet (WD; n = 24) or standard diet (SD; n = 24) for ten weeks to induce endothelial dysfunction, after which half of the animals in each group (n = 12) were allocated to receive B. subtilis DE111 (hereafter, PB) formulated into the diet for an additional eight weeks. Outcomes included endothelial-dependent arterial dilation, glucose tolerance, body weight changes, microbiota profiles, and assessments of intestinal permeability and mucosal immunity markers. Furthermore, a cell culture model of gut barrier function was used to assess the effects of PB on gut barrier integrity. PB treatment significantly attenuated WD-induced mesenteric endothelial-dependent arterial dilation, independent of changes in other cardiometabolic parameters or changes in gut barrier function. In vitro trans-epithelial electrical resistance of the Caco-2 cell culture confirmed that neither PB-conditioned media nor faecal waters from B. subtilis-treated human stool resulted in gut barrier improvements, nor did they protect against inflammation-associated barrier disruptions. Unsurprisingly, microbiota analysis revealed significant differences in Shannon's alpha diversity of WD-fed animals compared to SD. These data suggest that PB consumption significantly attenuated WD diet-induced endothelial dysfunction; however, the underlying mechanisms of this protection were not determined. Improvement in endothelial function was independent of PB-mediated changes to body weight or gut barrier function. Further studies should explore B. subtilis-mediated immune responses or metabolite production as mechanisms underlying these endothelial protective effects.
Research Insights
| Supplement | Dose | Health Outcome | Effect Type | Effect Size | Source |
|---|---|---|---|---|---|
| Bacillus subtilis DE111 | — | Improved Gut Barrier Function | Neutral | Small | View sourceneither PB-conditioned media nor faecal waters from B. subtilis-treated human stool resulted in gut barrier improvements, nor did they protect against inflammation-associated barrier disruptions |
| Bacillus subtilis DE111 | — | Improved Vascular Endothelial Function | Beneficial | Moderate | View sourcePB consumption significantly attenuated WD diet-induced endothelial dysfunction |
| Bacillus subtilis DE111 | — | No Change in Body Weight or Cardiometabolic Parameters | Neutral | Small | View sourceindependent of changes in other cardiometabolic parameters or changes in gut barrier function |