Lactobacillus Plantarum NC8 and its metabolite acetate alleviate type 1 diabetes via inhibiting NLRP3

Yuting Zhang; Yanning Li; Xiuquan Wang; Jingshu Huang; Xize Feng; Chunwei Shi; Wentao Yang; Yanlong Jiang; Xin Cao; Jianzhong Wang; Haibin Huang; Yan Zeng; Nan Wang; Guilian Yang; Chunfeng Wang

doi:10.1016/j.micpath.2023.106237

Lactobacillus Plantarum NC8 and its metabolite acetate alleviate type 1 diabetes via inhibiting NLRP3

Microb Pathog. 2023 Sep:182:106237. doi: 10.1016/j.micpath.2023.106237. Epub 2023 Jul 6.

Authors

Affiliations

¹ College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China.
² College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China. Electronic address: wangnan2020@jlau.edu.cn.
³ College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China. Electronic address: yangguilian@jlau.edu.cn.
⁴ College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, China. Electronic address: wangchunfeng@jlau.edu.cn.

PMID: 37422174
DOI: 10.1016/j.micpath.2023.106237

Abstract

A healthy organism is the result of host-microbiome co-evolution. Microbial metabolites can also stimulate immune cells to reduce intestinal inflammation and permeability. Gut dysbiosis will lead to a variety of autoimmune diseases, such as Type 1 diabetes (T1D). Most of probiotics, such as Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidium, and Streptococcus thermophiles, can improve the intestinal flora structure of the host, reduce intestinal permeability, and relieve symptoms of T1D patients if ingested above probiotics in sufficient amounts. Lactobacillus Plantarum NC8, a kind of Lactobacillus, whether it has an effect on T1D, and the mechanism of it regulating T1D is still unclear. As a member of the inflammatory family, NLRP3 inflammasome can enhance inflammatory responses by promoting the production and secretion of proinflammatory cytokines. Many previous studies had shown that NLRP3 also plays an important role in the development of T1D. When the NLRP3 gene is deleted, the disease progression of T1D will be delayed. Therefore, this study investigated whether Lactobacillus Plantarum NC8 can alleviate T1D by regulating NLRP3. The results demonstrated that Lactobacillus Plantarum NC8 and its metabolites acetate play a role in T1D by co-modulating NLRP3. Lactobacillus Plantarum NC8 and acetate can reduce the damage of T1D in the model mice, even if orally administered them in the early stage of T1D. The number of Th1/Th17 cells in the spleen and pancreatic lymph nodes (PLNs) of T1D mice were significantly reduced by oral Lactobacillus Plantarum NC8 or acetate. The expression of NLRP3 in the pancreas of T1D mice or murine macrophages of inflammatory model were significantly inhibited by treatment with Lactobacillus Plantarum NC8 or acetate. In addition, the number of macrophages in the pancreas were significantly reduced by the treatment with Lactobacillus Plantarum NC8 or acetate. In summary, this study indicated that the regulatory mechanism of Lactobacillus Plantarum NC8 and its metabolite acetate to T1D maybe via inhibiting NLRP3 and provides a novel insights into the mechanism of the alleviated role of probiotics to T1D.

Keywords: Acetate; Lactobacillus plantarum NC8; NLRP3; Th1/Th17 cells; Type 1 diabetes.

MeSH terms

Animals
Diabetes Mellitus, Type 1* / therapy
Lactobacillus / genetics
Lactobacillus plantarum* / metabolism
Mice
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Probiotics* / pharmacology
Th1 Cells

Substances

NLR Family, Pyrin Domain-Containing 3 Protein