Modulation of intestinal microbiota by glycyrrhizic acid prevents high-fat diet-enhanced pre-metastatic niche formation and metastasis.
Mucosal Immunol
; 12(4): 945-957, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-30755716
ABSTRACT
High-fat diet (HFD) promotes lung pre-metastatic niche formation and metastasis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. Here we demonstrate that glycyrrhizic acid (GA) prevents HFD-enhanced pre-metastatic niche formation and metastasis through gut microbiota. GA reduced HFD-enhanced myeloid-derived suppressor cell recruitment, pro-metastatic protein S100A8/A9 expression and metastasis burden of 4T1 breast cancer and B16F10 melanoma, accompanied by gut microbiota alteration and colonic macrophage polarization far away the M1-like phenotype. These parameters were greatly decreased by treatment with antibiotics, recolonization of Desulfovibrio vulgaris and Clostridium sordellii, and administration of lipopolysaccharide or deoxycholic acid. Macrophage depletion attenuated HFD-enhanced pre-metastatic niche formation and metastasis, but failed to further affect the effects of GA. Mechanistically, counteraction of HFD-enhanced gut microbiota dysbiosis by GA inhibited Gr-1+ myeloid cell migration and S100A8/A9 expression through decreasing the proportion of M1-like macrophages and their production of CCL2 and TNF-α in the colons via LPS/HMGB1/NF-κB signaling inactivation. Together, targeting the gut microbiota by GA to modulate colonic macrophages could be a novel strategy for the prevention of HFD-enhanced pre-metastatic niche formation and metastasis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_zoonosis
Asunto principal:
Ácido Glicirrínico
/
Microambiente Tumoral
/
Dieta Alta en Grasa
/
Microbioma Gastrointestinal
/
Antiinflamatorios
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mucosal Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China