Sự điều tiết của vi sinh vật đường ruột đối với P-glycoprotein trong biểu mô ruột để duy trì sự ổn định sinh lý

Microbiome - Tập 9 Số 1 - 2021
Sage E. Foley1, Christine Tuohy2, Merran Dunford3, Michael J. Grey4, Heidi De Luca4, Caitlin Cawley1, Rose L. Szabady5, Ana Maldonado‐Contreras1, Jean Marie Houghton6, Doyle V. Ward1, Randall J. Mrsny3, Beth A. McCormick1
1Program in Microbiome Dynamics, University of Massachusetts Medical School, Worcester, USA
2Graduate School of Nursing, University of Massachusetts Medical School, Worcester, USA
3Department of Pharmacy & Pharmacology; University of Bath; Bath BA2 7AY UK
4Division of Gastroenterology and Nutrition, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
5Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605, USA
6Division of Gastroenterology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA

Tóm tắt

Tóm tắtĐặt vấn đềP-glycoprotein (P-gp) đóng vai trò quan trọng trong việc bảo vệ biểu mô ruột thông qua khả năng trung gian sự thoát ra của thuốc/chất ngoại lai từ niêm mạc ruột vào lòng ruột. Các nghiên cứu gần đây chỉ ra rằng P-gp cũng là cầu nối quan trọng trong giao tiếp giữa chức năng hàng rào niêm mạc ruột và hệ thống miễn dịch bẩm sinh. Tuy nhiên, mặc dù đã có hiểu biết trong hơn 10 năm về vai trò trung tâm của P-gp trong cân bằng sinh lý đường tiêu hóa, cơ chế phân tử chính xác điều khiển sự biểu hiện và điều hòa chức năng của nó vẫn chưa được làm rõ. Trong nghiên cứu này, chúng tôi đã đánh giá cách mà hệ vi sinh vật đường ruột thúc đẩy sự biểu hiện và chức năng của P-gp.Kết quảChúng tôi đã xác định được một “cốt lõi chức năng” của vi sinh vật trong cộng đồng ruột, cụ thể là các chi trong các lớp Clostridia và Bacilli, là cần thiết và đủ để kích thích sự biểu hiện của P-gp trong biểu mô ruột trong các mô hình chuột. Phân tích metagenomic của cộng đồng vi sinh vật này cho thấy rằng sự sản xuất axit béo chuỗi ngắn và axit mật thứ cấp có liên quan tích cực đến sự biểu hiện của P-gp. Chúng tôi cũng đã chỉ ra rằng hai loại chuyển hoá từ vi sinh vật này có tác dụng hiệp đồng làm tăng cường sự biểu hiện và chức năng của P-gp cả trong ống nghiệm và trong cơ thể sống. Hơn nữa, trong các bệnh nhân mắc bệnh viêm loét đại tràng (UC), chúng tôi phát hiện sự biểu hiện của P-gp giảm đi kèm với sự giảm của các endocannabinoids chống viêm nguồn gốc từ biểu mô và nội dung lòng ruột (ví dụ: vi khuẩn hoặc các chuyển hoá của chúng) với khả năng giảm để kích thích biểu hiện P-gp.

Từ khóa

#P-glycoprotein #vi sinh vật đường ruột #biểu mô ruột #cân bằng sinh lý #viêm niêm mạc

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