Live probiotic bacteria administered in a pathomimetic Leaky Gut Chip ameliorate impaired epithelial barrier and mucosal inflammation.
Sci Rep
; 12(1): 22641, 2022 12 31.
Article
en En
| MEDLINE
| ID: mdl-36587177
ABSTRACT
Here, we report a pathomimetic Leaky Gut Chip that recapitulates increased epithelial permeability and intestinal inflammation to assess probiotic intervention as live biotherapeutics. We leveraged a mechanodynamic human gut-on-a-chip (Gut Chip) that recreates three-dimensional epithelial layers in a controlled oxygen gradient and biomechanical cues, where the addition of a cocktail of pro-inflammatory cytokines, TNF-α and IL-1ß, reproducibly induced impaired epithelial barrier followed by intestinal inflammation. This inflamed leaky epithelium was not recovered for up to 3 days, although the cytokine treatment ceased. However, when probiotic bacteria, either Lactobacillus rhamnosus GG or a multi-species mixture (VSL#3), were respectively administered on the leaky epithelium, bacterial cells colonized mucosal surface and significantly improved barrier function, enhanced the localization of tight junction proteins such as ZO-1 and occludin, and elevated mucus production. In addition, inflammatory markers, including p65, pSTAT3, and MYD88, that were highly expressed in the germ-free control were significantly reduced when probiotic bacteria were co-cultured in a Leaky Gut Chip. Probiotic treatment also significantly reduced the production of secretory pro-inflammatory cytokines. Hence, our pathomimetic Leaky Gut Chip may offer a translational strategy to dissect the therapeutic mechanism of live biotherapeutic products and validate their clinical potential by incorporating patient-derived organoids.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Citocinas
/
Probióticos
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos