Hierarchy‐Assembled Dual Probiotics System Ameliorates Cholestatic Drug‐Induced Liver Injury via Gut‐Liver Axis Modulation

Abstract

Cholestatic drug‐induced liver injury (DILI) induced by drugs or other xenobiotics is a severe and even fatal clinical syndrome. Here, living materials of hierarchy‐assembled dual probiotics system are fabricated by sequentially encapsulating probiotic Lactobacillus delbrueckii subsp. bulgaricus (LDB) and Lactobacillus rhamnosus GG (LGG) into Ca2+‐complexed polymer microspheres for effective prevention of cholestatic DILI. Upon entering intestinal tract of the constructed living materials, LGG is released because of pH‐triggered dissolution of outer enteric polymer coating. The released LGG can inhibit hepatic bile acids (BAs) synthesis by activating intestinal farnesoid X receptor‐fibroblast growth factor 15（FGF‐15) signaling pathway. BAs excretion is also facilitated by LGG through increasing the abundance of bile salt hydrolase (BSH)‐active gut commensal bacteria. Furthermore, exposed positively‐charged chitosan shell can absorb the excessive BAs via electrostatic interaction, which leads to steady BAs fixation by the imprisoned LDB, decreasing the total BAs amounts in enterohepatic circulation. Together, the fabricated living materials, obtained here, can effectively prevent cholestatic DILI through dredging cholestasis via gut‐liver axis modulation. The therapeutic effect is demonstrated in α‐naphthylisothiocyanate and clinical antiepileptic drug valproate acid‐induced cholestatic DILI mouse models, which reveal the great potential for effective cholestatic DILI management.

Nanocrystalline Cellulose Cures Constipation via Gut Microbiota Metabolism

“…NCC could significantly increase the relative abundances of Lactobacillus , Prevotellaceae_UCG-001 , and Anaerotruncus , which would affect the levels of SCFAs, farnesoid X receptor (FXR) pathways, Takeda G-protein-coupled receptor 5 (TGR5) pathways, glucose homeostasis, fermentation capacity of gut microbiota, and intestinal motility. Lactobacillus could promote intestinal motility by increasing the contents of butyric acid and acetic acid and regulate bile acids, lipid, and glucose homeostasis by activating FXR and TGR5 signaling pathway. − Prevotellaceae_UCG-001 and Anaerotruncus could increase the content of butyric acid, regulate glucose homeostasis by participating in glucose metabolism, and make the fermentation capacity of gut microbiota toward the benefit of the host. , …”

Cholestasis impairs gut microbiota development and bile salt hydrolase activity in preterm neonates

“… 48 Bile acid secretion is stimulated by similar mechanisms in a mouse model of drug-induced cholestasis by L. rhamnosus GG and other probiotic bacteria. 49 Although a causal relationship between decreased BSH activity and neonatal cholestasis remains unknown, BSH-based probiotic therapy is an intriguing potential therapeutic avenue. It is notable that our cholestatic neonates were on total parenteral nutrition for a longer duration of time than the control cohort and that half of the cholestatic infants developed NEC (2/6 patients required surgery).…”

Cholestasis: exploring the triangular relationship of gut microbiota-bile acid-cholestasis and the potential probiotic strategies

“…It can be concluded that LGG treatment helps alleviate ICP and cholestatic liver injury, which can be a potential therapeutic strategy for ICP. Chen et al 16 further demonstrated the great potential of LGG to alleviate cholestasis in mice model of cholestasis induced by α-naphthylisothiocyanate (ANIT) and clinical antiepileptic drugs valproate acid (VPA).…”

“… 9 , 15 In some recent studies, the beneficial effects of probiotics on cholestasis have also been demonstrated. 16 , 17 Therefore, we reviewed the triangular relationship among gut microbiota, BA and cholestasis, revealing the potential role and possible mechanism of probiotics in the treatment of cholestasis.…”