Microbiota and Nod-like receptors balance inflammation and metabolism during obesity and diabetes

• Published in: Biomedical Journal Vol. 46; no. 5; p. 100610
• Main Authors: Rodrigues E-Lacerda, Rodrigo, Fang, Han, Robin, Nazli, Bhatwa, Arshpreet, Marko, Daniel M, Schertzer, Jonathan D
• Format: Journal Article
• Language: English
• Published: United States Chang Gung University 01-10-2023; Elsevier
• Subjects: Glucose; Insulin; Insulin resistance; Microbiome; Microbiota; Obesity; Review; microbiota; glucose; insulin; T2D; NLRs; insulin resistance; microbiome; obesity
• ISSN: 2319-4170; 2320-2890
• DOI: 10.1016/j.bj.2023.100610

Gut microbiota influence host immunity and metabolism during obesity. Bacterial sensors of the innate immune system relay signals from specific bacterial components (i.e., postbiotics) that can have opposing outcomes on host metabolic inflammation. NOD-like receptors (NLRs) such as Nod1 and Nod2 both recruit receptor-interacting protein kinase 2 (RIPK2) but have opposite effects on blood glucose control. Nod1 connects bacterial cell wall-derived signals to metabolic inflammation and insulin resistance, whereas Nod2 can promote immune tolerance, insulin sensitivity, and better blood glucose control during obesity. NLR family pyrin domain containing (NLRP) inflammasomes can also generate divergent metabolic outcomes. NLRP1 protects against obesity and metabolic inflammation potentially because of a bias toward IL-18 regulation, whereas NLRP3 appears to have a bias toward IL-1β-mediated metabolic inflammation and insulin resistance. Targeting specific postbiotics that improve immunometabolism is a key goal. The Nod2 ligand, muramyl dipeptide (MDP) is a short-acting insulin sensitizer during obesity or during inflammatory lipopolysaccharide (LPS) stress. LPS with underacylated lipid-A antagonizes TLR4 and counteracts the metabolic effects of inflammatory LPS. Providing underacylated LPS derived from Rhodobacter sphaeroides improved insulin sensitivity in obese mice. Therefore, certain types of LPS can generate metabolically beneficial metabolic endotoxemia. Engaging protective adaptive immunoglobulin immune responses can also improve blood glucose during obesity. A bacterial vaccine approach using an extract of the entire bacterial community in the upper gut promotes protective adaptive immune response and long-lasting improvements in blood glucose control. A key future goal is to identify and combine postbiotics that cooperate to improve blood glucose control.